Causal relationship between anti-inflammatory drugs and cancer: a pan-cancer study with Mendelian randomization.

Background: Numerous epidemiological studies have elucidated the intricate connection between inflammation and cancer, highlighting how sustained inflammatory responses can fuel carcinogenesis by fostering proliferation, angiogenesis, and metastasis, while dampening immune responses and sensitivity to chemotherapy. Previous clinical investigations have underscored the potential of anti-inflammatory medications in either preventing or mitigating tumor formation. Here, the causal relationship between anti-inflammatory drugs and cancer was further explored through Mendelian randomization studies. Methods: Employing Mendelian randomization, we scrutinized the causal links between three anti-inflammatory drugs-NSAIDs, Aspirin, and Anilide-and 37 types of cancer. We primarily utilized inverse variance weighting (IVW) as the primary analytical approach to delineate the causal association between these drugs and cancer types. Concurrently, sensitivity analyses were conducted to ascertain the absence of horizontal pleiotropy and heterogeneity. Results: Our investigation revealed a discernible causal relationship between certain anti-inflammatory drugs and a subset of cancers, albeit without a pervasive impact across all cancer types. Specifically, NSAIDs exhibited a risk-reducing effect on non-small cell lung cancer (OR: 0.76, 95% CI: 0.59-0.97, p-value: 0.03) and gastric cancer (OR: 0.57, 95% CI: 0.34-0.98, p-value: 0.04). Conversely, aspirin was associated with an increased risk of oral malignant tumors (OR: 2.18, 95% CI: 1.13-4.21, p-value: 0.02). Notably, no statistically significant findings were observed for anilide drugs (p < 0.05). Conclusion: We identified several cancers with potential causal links to NSAIDs, including non-small cell lung cancer and gastric cancer. Despite our extensive analysis, we did not identify a substantial causal relationship between the use of anti-inflammatory drugs and the development of various cancers.

Subclone from CT26 resistant to anti-PD-1 therapy associated with increased expression of genes related to glucocorticoids.

BACKGROUND: Although the use of anti-PD-1 antibodies has fundamentally changed traditional cancer treatment, most patients are resistant to anti-PD-1 treatment. Glucocorticoids (GCs) play an important role in tumorigenesis and tumor progression, but the role of endogenous GCs in resistance to anti-PD-1 antibody therapy remains unclear. METHODS: Single cell-derived cell lines (SCDCLs) were generated from a colorectal cancer cell line (CT26) using limiting dilution. We analyzed tumor tissues from anti-PD-1 antibody-treated and untreated mice inoculated with SCDCLs via transcriptome sequencing and flow cytometry to detect pathway activity and immune cell composition changes in the tumor microenvironment. RESULTS: Five SCDCLs were inoculated into wild-type BALB/c mice (all tumorigenic). Single-cell clone (SCC)-2 exhibited the slowest growth rates both in vivo and in vitro compared to other single-cell clones, and better long-term survival than SCC1 and CT26. Flow cytometry showed that SCC2 tumor-bearing mice exhibited significantly higher infiltration of T cells within the tumor tissue, and higher expression of PD-1 on these T cells than the other groups in vivo. However, the SCC2 group showed no response to anti-PD-1 therapy. Transcriptome analysis revealed that the SCC2 group exhibited increased expression of genes related to GC (Hsd11b1, Sgk3, Tgfbr2, and Il7r) compared to SCC2-anti-PD-1 treated tumors. CONCLUSIONS: GC pathway activation is related to resistance to anti-PD-1 therapy.

A haplotype-resolved genome assembly of Malus domestica 'Red Fuji'.

The 'Red Fuji' apple (Malus domestica), is one of the most important and popular economic crops worldwide in the fruit industry. Using PacBio HiFi long reads and Hi-C reads, we assembled a high-quality haplotype-resolved genome of 'Red Fuji', with sizes of 668.7 and 668.8 Mb, and N50 sizes of 34.1 and 31.4 Mb. About 97.2% of sequences were anchored in 34 chromosomes. We annotated both haploid genomes, identifying a total of 95,439 protein-coding genes in the two haplotype genomes, with 98% functional annotation. The haplotype-resolved genome of 'Red Fuji' apple stands as a precise benchmark for an array of analyses, such as comparative genomics, transcriptomics, and allelic expression studies. This comprehensive resource is paramount in unraveling variations in allelic expression, advancing quality improvements, and refining breeding efforts.

HortGenome Search Engine, a universal genomic search engine for horticultural crops.

Horticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE; http://hort.moilab.net), which allows for the querying of genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 500 horticultural crops. In addition, four commonly used tools, including 'BLAST', 'Batch Query', 'Enrichment analysis', and 'Synteny Viewer' have been developed for efficient mining and analysis of these genomic data.

Nanofiber-induced hierarchically-porous magnesium phosphate bone cements accelerate bone regeneration by inhibiting Notch signaling.

Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM in vivo. Overall, our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.

Using machine learning algorithms based on patient admission laboratory parameters to predict adverse outcomes in COVID-19 patients.

Amidst the global COVID-19 pandemic, the urgent need for timely and precise patient prognosis assessment underscores the significance of leveraging machine learning techniques. In this study, we present a novel predictive model centered on routine clinical laboratory test data to swiftly forecast patient survival outcomes upon admission. Our model integrates feature selection algorithms and binary classification algorithms, optimizing algorithmic selection through meticulous parameter control. Notably, we developed an algorithm coupling Lasso and SVM methodologies, achieving a remarkable area under the ROC curve of 0.9277 with the use of merely 8 clinical laboratory parameters collected upon admission. Our primary contribution lies in the utilization of straightforward laboratory parameters for prognostication, circumventing data processing intricacies, and furnishing clinicians with an expeditious and precise prognostic assessment tool.

FOXP4-mediated induction of PTK7 activates the Wnt/ß-catenin pathway and promotes ovarian cancer development.

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Associations of dietary factors with gastric cancer risk: insights from NHANES 2003-2016 and mendelian randomization analyses.

Background: Gastric cancer (GC) continues to be one of the leading causes of cancer-related deaths globally. Diet significantly influences the incidence and progression of GC. However, the relationship between dietary intake and GC is inconsistent. Methods: A study was conducted with adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2016 to investigate possible associations between 32 dietary factors and GC. To further detect potential causal relationships between these dietary factors and the risk of GC, a two-sample Mendelian randomization (MR) analysis was conducted. The primary method employed was the inverse variance weighted (IVW) analysis, and its results were further validated by four other methods. Results: Of the 35,098 participants surveyed, 20 had a history of GC. Based on the results of weighted logistic multivariate analysis, it was observed that there was a positive correlation between total fat intake [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.01-1.17), p = 0.03] and GC as well as negative association of dietary monounsaturated fatty acids (MUFAs) intake [OR = 0.83, 95% CI: (0.76-0.92), p < 0.001]. Further evaluations of the odds of GC across the quartiles of dietary MUFAs showed that the top quartile of total MUFA intake was associated with a lower likelihood of GC in three different models [model1: OR = 0.03, 95% CI: (0.00-0.25), p < 0.01; model2: OR = 0.04, 95% CI: (0.00-0.38), p = 0.01; model3: OR = 0.04, 95% CI: (0.00-0.40), p = 0.01]. For the MR analyses, genetic instruments were selected from the IEU Open GWAS project; IVW analysis showed that GC risk was not associated with MUFAs [OR = 0.82, 95% CI: (0.59-1.14), p = 0.23] or the ratio of MUFAs to total fatty acids [OR = 1.00, 95% CI: (0.75-1.35), p = 0.98]. Similar results were observed when using the other MR methods. Conclusion: The NHANES study revealed that consuming MUFAs was linked to a lower risk of GC, although the results of MR analyses do not provide evidence of a causal relationship. Additional research is therefore necessary to clarify these findings.

Novel aptasensor based on polyaniline functionalized carboxylated dobby carbon nanotubes and molybdenum disulfide for endotoxin detection.

Endotoxins, also known as lipopolysaccharides (LPS), are present within the cell walls of Gram-negative bacteria and are released upon cellular death, which can pose a significant risk to human and animal health. Due to the minimal amount of endotoxin required to trigger an inflammatory response in human body, the demand for sensitive methods with low endotoxin detection limits is essential necessary. This paper presents a straightforward aptamer sensor which can enhance the conductivity and specific surface area of molybdenum disulfide (MoS2) by incorporating carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) and polyaniline (PANI). Doping with gold nanoparticles (AuNPs) improves biocompatibility and sensitivity while providing binding sites for thiolated endotoxin-binding aptamers (LBA). This biosensor achieved a remarkable detection limit as low as 0.5 fg mL-1, enabling trace-level identification of LPS. It also exhibits excellent repeatability, selectivity, and stability, facilitating rapid and accurate LPS detection. Moreover, this method demonstrates high recovery rates and specificity for LPS analysis in food samples, showcasing its promising application prospects in trace-level LPS detection within the food industry.

Structural optimization of Moracin M as novel selective phosphodiesterase 4 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF.

The chromosome-level genome assembly of the dwarfing apple interstock Malus hybrid 'SH6'.

Malus hybrid 'SH6' (M. honanensis × M. domestica)is a commonly used apple interstock in China, known for its excellent dwarfing characteristics and cold tolerance. In this study, a combined strategy utilizing PacBio HiFi, Hi-C and parental resequencing data were employed to assemble two haploid genomes for 'SH6'. After chromosome anchoring, the final hapH genome size was 596.63 Mb, with a contig N50 of 34.38 Mb. The hapR genome was 649.37 Mb, with a contig N50 of 36.84 Mb. Further analysis predicted that repeated sequences made up 59.69% and 62.52% of the entire genome, respectively. Gene annotations revealed 45,435 genes for hapH and 48,261 genes for hapR. Combined with genomic synteny we suggest that the hapR genome originates from its maternal parent M. domestica cv. Ralls Janet, while the hapH genome comes from its paternal parent, M. honanensis. The assembled genome significantly contributes to the discovery of genes associated with apple dwarfing and the molecular mechanisms governing them.

Neoadjuvant targeted immunotherapy followed by surgical resection versus upfront surgery for hepatocellular carcinoma with macrovascular invasion: A multicenter study.

Background: This study aimed to investigate the safety and efficacy of preoperative targeted immunotherapy followed by surgical resection for hepatocellular carcinoma (HCC) patients with macrovascular invasion. Method: Clinical information of HCC patients with macrovascular invasion was collected from four medical centers. These patients were divided into two cohorts: the upfront surgery group (n=40) and the neoadjuvant group (n=22). Comparisons between the two groups were made with appropriate statistical methods. Results: HCC Patients with macrovascular invasion in the neoadjuvant group were associated with increased incidence of postoperative ascites (72.73% vs. 37.5%, P=0.008), but shorter postoperative hospital stay (10 days vs. 14 days, P=0.032). Furthermore, targeted immunotherapy followed by surgical resection significantly reduced the postoperative recurrence rate at both 3 months and 1 year (9% versus 28.9%, 32.1% versus 67.9%, respectively; P=0.018), but increased the postoperative nononcologic mortality rate within 1 year (20.1% vs. 2.8%; P= 0.036). Conclusion: For HCC patients with macrovascular invasion, preoperative targeted immunotherapy significantly decreased the postoperative tumor recurrence rate while maintaining relative safety, but such a treatment may also result in chronic liver damage and increased risk of nononcologic mortality.

Monolithically integrated micro-supercapacitors with high areal number density produced by surface adhesive-directed electrolyte assembly.

Accurately placing very small amounts of electrolyte on tiny micro-supercapacitors (MSCs) arrays in close proximity is a major challenge. This difficulty hinders the development of densely-compact monolithically integrated MSCs (MIMSCs). To overcome this grand challenge, we demonstrate a controllable electrolyte directed assembly strategy for precise isolation of densely-packed MSCs at micron scale, achieving scalable production of MIMSCs with ultrahigh areal number density and output voltage. We fabricate a patterned adhesive surface across MIMSCs, that induce electrolyte directed assembly on 10,000 highly adhesive MSC regions, achieving a 100 µm-scale spatial separation between each electrolyte droplet within seconds. The resultant MIMSCs achieve an areal number density of 210 cells cm-2 and a high areal voltage of 555 V cm-2. Further, cycling the MIMSCs at 190 V over 9000 times manifests no performance degradation. A seamlessly integrated system of ultracompact wirelessly-chargeable MIMSCs is also demonstrated to show its practicality and versatile applicability.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

Available heavy metals concentrations in agricultural soils: Relationship with soil properties and total heavy metals concentrations in different industries.

Heavy metal (HM) pollution in agricultural soils has arisen sharply in recent years. However, the impact of main factors on available HMs concentrations in agricultural soils of the three main industries (smelting, chemical and mining industry) is unclear. Herein, soil properties (pH, cation exchange capacity (CEC) and texture (sand, slit, clay)), total and available concentrations were concluded based on the results of 165 research papers from 2000 to 2023 in Web of Science database. In the three industries, the correlation and redundancy analysis were used to study the correlation between main factors and available concentrations, and quantitatively analyzed the contribution of each factor to available concentrations with gradient boosting decision tree model. The results showed that different factors had varying degrees of impact on available metals in the three main industries, and the importance of same factors varied in each industry, as for soil pH, it was most important for available Pb and Zn in the chemical industry, but the total concentrations were most important in the smelting and mining industry. There was no significant correlation between total and available concentrations. Soil properties involved in this paper (especially soil pH) were negatively correlated with available concentrations. This study provides effective guidance for the formulation of soil pollution control and risk assessment standards based on industry classification in the three major industrial impact areas.

Expressions of CXCR3 and PD-1 on T cells and their clinical relevance in colorectal cancer.

PURPOSE: Clinical application of immunotherapy represented by Programmed Death-1 (PD-1) monoclonal antibody has changed the treatment paradigm for colorectal cancer (CRC), and tumor-infiltrating T lymphocytes are critical for anti-PD-1 therapy in CRC. However, there are few studies on the relationship between the expression CXCR3 on T lymphocytes and the clinical aspects of CRC. In this study, we analyzed the expression levels of CXCR3 and PD-1 in CD8+ and CD4+ T lymphocytes in healthy donors (HDs) and patients with CRC. METHODS: We detected the expressions of CXCR3 and PD-1 on T lymphocytes in peripheral blood of healthy donors as well as peripheral blood, tumor tissue and para-cancerous tissues of patients with CRC using flow cytometry. We also analyzed the relationship between the expressions of CXCR3 and PD-1 on T lymphocytes and the pathological characteristics of CRC using t test. RESULTS: Expression of CXCR3 on tumor-infiltrating T lymphocytes was lower, whereas the expression of PD-1 was higher than that on para-cancerous tissues and PB in patients with CRC. In patients with lymph node metastasis of CRC, the expressions levels of CXCR3+ PD-1+ on tumor-infiltrating CD8+ and CD4+ T lymphocytes were higher than those in patients without lymph node metastasis. The levels of CXCR3+ PD-1+ expressions differed depending on the primary tumor site. CONCLUSION: Expressions of CXCR3 and PD-1 on tumor-infiltrating T lymphocytes are related to the development of CRC and metastasis, providing clues for exploring the pathogenesis of CRC and developing new strategies for tumor immunotherapy.

Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling.

Key gene mutations are essential for colorectal cancer (CRC) development; however, how the mutated tumor cells impact the surrounding normal cells to promote tumor progression has not been well defined. Here, we report that PIK3CA mutant tumor cells transmit oncogenic signals and result in malignant transformation of intestinal epithelial cells (IECs) via paracrine exosomal arachidonic acid (AA)-induced H3K4 trimethylation. Mechanistically, PIK3CA mutations sustain SGK3-FBW7-mediated stability of the cPLA2 protein, leading to the synthetic increase in AA, which is transported through exosome and accumulated in IECs. Transferred AA directly binds Menin and strengthens the interactions of Menin and MLL1/2 methyltransferase. Finally, the combination of VTP50469, an inhibitor of the Menin-MLL interaction, and alpelisib synergistically represses PDX tumors harboring PIK3CA mutations. Together, these findings unveil the metabolic link between PIK3CA mutant tumor cells and the IECs, highlighting AA as the potential target for the treatment of patients with CRC harboring PIK3CA mutations.

Metal telluride nanosheets by scalable solid lithiation and exfoliation.

Transition metal tellurides (TMTs) have been ideal materials for exploring exotic properties in condensed-matter physics, chemistry and materials science1-3. Although TMT nanosheets have been produced by top-down exfoliation, their scale is below the gram level and requires a long processing time, restricting their effective application from laboratory to market4-8. We report the fast and scalable synthesis of a wide variety of MTe2 (M = Nb, Mo, W, Ta, Ti) nanosheets by the solid lithiation of bulk MTe2 within 10 min and their subsequent hydrolysis within seconds. Using NbTe2 as a representative, we produced more than a hundred grams (108 g) of NbTe2 nanosheets with 3.2 nm mean thickness, 6.2 µm mean lateral size and a high yield (>80%). Several interesting quantum phenomena, such as quantum oscillations and giant magnetoresistance, were observed that are generally restricted to highly crystalline MTe2 nanosheets. The TMT nanosheets also perform well as electrocatalysts for lithium-oxygen batteries and electrodes for microsupercapacitors (MSCs). Moreover, this synthesis method is efficient for preparing alloyed telluride, selenide and sulfide nanosheets. Our work opens new opportunities for the universal and scalable synthesis of TMT nanosheets for exploring new quantum phenomena, potential applications and commercialization.

Microbiota-derived acetate attenuates neuroinflammation in rostral ventrolateral medulla of spontaneously hypertensive rats.

BACKGROUND: Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear. METHODS: The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured. RESULTS: The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis. CONCLUSIONS: Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.

Clinical value of coagulation parameters in predicting the severity of severe fever with thrombocytopenia syndrome.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis. Methods: A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves. Results: Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant (p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant (p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively). Discussion: The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient's condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease.