Impact of lung adenocarcinoma subtypes on survival and timing of brain metastases.

Purpose: Lung cancer is a devastating disease, with brain metastasis being one of the most common distant metastases of lung adenocarcinoma. This study aimed to investigate the prognostic characteristics of individuals with brain metastases originating from invasive lung adenocarcinoma of distinct pathological subtypes, providing a reference for the management of these patients. Methods: Clinical data from 156 patients with lung adenocarcinoma-derived brain metastases were collected, including age, sex, smoking status, Karnofsky Performance Status scores, pathological subtype, lymph node metastasis, tumor site, treatment mode, T stage, and N stage. Patients were classified into two groups (highly differentiated and poorly differentiated) based on their pathological subtypes. Propensity score matching was used to control for confounding factors. The prognostic value of pathological subtypes was assessed using Kaplan-Meier analysis and Cox proportional hazards regression modeling. Results: Kaplan-Meier analysis indicated that patients in the moderately to highly differentiated group had better prognoses. Multivariate analysis revealed that being in the poorly differentiated group was a risk factor for poorer prognosis. Thoracic tumor radiation therapy, chemotherapy, and surgery positively influenced the time interval between lung cancer diagnosis and brain metastasis. Conclusions: The pathological subtypes of lung adenocarcinoma-derived brain metastases are associated with patient prognosis. Patients in the poorly differentiated group have worse prognoses compared to those in the moderately to highly differentiated group. Therefore, patients in the poorly differentiated group may require more frequent follow-ups and aggressive treatment.

A Novel Inflammatory Marker: Relationship Between Red Cell Distribution Width/Albumin Ratio and Vascular Complications in Patients with Type 2 Diabetes Mellitus.

Purpose: To explore the relationship between Red cell distribution width/albumin ratio (RAR) and vascular complications, including atherosclerosis of the lower limbs, diabetic nephropathy(DN), and diabetic retinopathy(DR), in patients with type 2 diabetes mellitus(T2DM). Patients and Methods: The study included 427 patients with type 2 diabetes mellitus who were hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Jinan University (Guangzhou, China) between April 1, 2022 and May 31, 2023. Baseline characteristics were displayed according to the quartiles of the RAR. Logistic regression analysis and receiver operating characteristic curves (ROC) were used to analyze the data. Results: After adjusting for confounders, a higher RAR quartile(the fourth quartile) was associated with an increased risk of atherosclerosis of the lower limbs(OR: 2.973, 95% CI 1.281-6.906, p = 0.011), and diabetic nephropathy(OR: 2.876, 95% CI 1.315-6.287, p = 0.008) compared to the lowest RAR quartile. The patients were further divided into two groups according to urinary albumin to creatinine ratio (UACR≥30mg/g and UACR < 30mg/g) and Glomerular Filtration Rate (eGFR<60 mL·min⁻¹ (1.73 m²) ⁻¹ and eGFR≥60 mL·min⁻¹ (1.73 m²) ⁻¹). Similar results were observed. However, We found that RAR quartile did not significantly increase the likelihood of developing diabetic retinopathy(OR: 1.183, 95% CI 0.633-2.211, p = 0.598). Conclusion: The RAR ratio is associated with an increased risk of atherosclerosis of the lower limbs and diabetic nephropathy in patients with T2DM. The RAR ratio may be an important clinical marker of vascular complications in T2DM.

Stevens-Johnson Syndrome/Toxic epidermal necrolysis complicated with fulminant type 1 diabetes mellitus: a case report and literature review.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed ß-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. CASE PRESENTATION: We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally. CONCLUSIONS: This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis.

Identification of UNC5B as a novel aggressive biomarker for osteosarcoma based on basement membrane genes.

BACKGROUND: The prognosis of patients with metastatic osteosarcoma is poor, and the variation of basement membrane genes (BMGs) is associated with cancer metastasis. However, the role of BMGs in osteosarcoma has been poorly studied. METHODS: BMGs were collected and differentially expressed BMGs (DE-BMGs) were found through difference analysis. DE-BMGs were further screened by univariate Cox regression and Lasso regression analyses, and six key BMGs were identified and defined as basement membrane genes signatures (BMGS). Then, BMGS was used to construct the osteosarcoma BMGS risk score system, and the osteosarcoma patients were divided into high- and low-risk groups based on the median risk score. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE scores were used to investigate the differences in immune infiltration between the two scoring groups. Additionally, we investigated whether UNC5B affects various features in tumors by bioinformatic analysis and whether UNC5B was involved in multiple biological functions of osteosarcoma cells by wound healing assay, transwell assay, and western blot. RESULTS: The osteosarcoma BMGS risk score reliably predicts the risk of metastasis, patient prognosis, and immunity. UNC5B expression was elevated in osteosarcoma, and correlated with various characteristics such as immune infiltration, prognosis, and drug sensitivity. In vitro assays showed that UNC5B knockdown reduced osteosarcoma cells' capacity for migration and invasion, and EMT process. CONCLUSION: A novel BMGS risk score system that can effectively predict the prognosis of osteosarcoma was developed and validated. The UNC5B gene in this system is one of the key aggressive biomarkers of osteosarcoma.

Dysregulation of plasma circulating microRNAs in all-cause and cause-specific cancers: the Rotterdam Study.

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Mounting evidence underscores the dysregulation of miRNAs to be associated with cancer development and progression by acting as tumour suppressors and oncogenes. However, their potential as biomarkers for early diagnosis of different cancers remains incompletely unraveled. We explored the relationship between plasma circulatory miRNAs and cancer risk within the population-based Rotterdam Study cohort. Plasma samples were collected at baseline (between 2002 and 2005) and miRNA levels were measured in 1,999 participants, including 169 prevalent cancer cases. The occurrence of cancer was assessed by continuous monitoring of medical records in 1,830 cancer-free participants until January 1, 2015. We assessed the association between incidence of five common cancers (blood, lung, breast, prostate, and colorectal) and 591 miRNAs well-expressed in plasma, using adjusted Cox proportional-hazards regression models. Our longitudinal analysis identified 13 miRNAs significantly associated with incident hematologic tumors surpassing the Bonferroni-corrected P < 8.46 × 10- 5, 12 of them (miR-6124, miR-6778-5p, miR-5196, miR-654-5p, miR-4478, miR-4430, miR-4534, miR-1915-3p, miR-4644, miR-4292, miR-7111-5p, and miR-6870-5p) were also associated with prevalent hematologic tumors in the cross-sectional analysis at the baseline. In-silico analyses of the putative target genes of 13 identified miRNAs highlighted relevant genes and pathways linked to hematologic tumors. While no significant miRNA association was found for other four studied cancers, two miRNAs (miR-3157-5p and miR-3912-5p) showed nominal association with incident of three different cancer types. Overall, this study indicates that plasma levels of several miRNAs are dysregulated in hematologic tumors, highlighting their potential as biomarkers for early diagnosis as well as being involved in the pathogenesis of blood cancers.

Bubble-Guidance Breaking Gas Shield for Highly Efficient Overall Water Splitting.

Overall water splitting is a promising technology for sustainable hydrogen production, but the primary challenge is removing bubbles from the electrode surface quickly to increase hydrogen production. Inspired by the directional fluid transport properties of natural biological surfaces like Nepenthes peristome and Morpho butterfly's wings, here a strategy is demonstrated to achieve highly efficient overall water splitting by a bubble-guidance electrode, that is, an anisotropic groove-micro/nanostructured porous electrode (GMPE). Gradient groove micro/nanostructures on the GMPE serve as high-speed bubble transmission channels and exhibit superior bubble-guidance capabilities. The synergistic effect of the asymmetric Laplace pressure generated between microscale porous structure and groove patterns and the buoyancy along the groove patterns pushes the produced bubbles directionally to spread, transport, and detach from the electrode surface in time. Moreover, the low adhesive nanosheet arrays are beneficial to reduce bubble size and increase bubble release frequency, which cooperatively improve mass transfer with the microscale structure. Notably, GMPE outperforms planar-micro/nanostructured porous electrode (PMPE) in hydrogen/oxygen evolution reactions, with GMPE||GMPE showing better water splitting performance than commercially available RuO2||20 wt.% Pt/C. This work improves electrodes for better mass transfer and kinetics in electrochemical reactions at solid-liquid-gas interfaces, offering insight for designing and preparing gas-involved photoelectrochemical electrodes.

Sesquiterpenoids from Carpesium abrotanoides and their anti-inflammatory activity both in vitro and in vivo.

Twenty-nine sesquiterpenoids, including pseudoguaiane-type (1-11), eudesmane-type (12-23), and carabrane-type (24-29), have been identified from the plant Carpesium abrotanoides. Of them, compounds 1-4, 12-15, and 24-27, namely carpabrotins A-L, are twelve previously undescribed ones. Compound 3 possessed a pseudoguaiane backbone with a rearrangement modification at C-11, C-12 and C-13, while compound 4 suffered a carbon bond break between the C-4 and C-5 to form a rare 4,5-seco-pseudoguaiane lactone. Compounds 1-3, 5, 13-16 and 25-27 exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 macrophages with IC50 values less than 40 µM, while compounds 1, 2, 5, 13, 14, 16, and 25-27 showed significant inhibitory activity comparable to that of dexamethasone. The anti-atopic dermatitis (AD) effects of compounds 5 and 16 were tested according to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in KM mice, and the results revealed that the major products 5 and 16 improved the histological features of AD-like skin lesions and mast cell infiltration in mice. This study suggested that sesquiterpenoids in C. abrotanoides should play a key role in its anti-inflammatory use.

Multiomics-Based Biocargo Components Analysis in Enterococcus faecium Membrane Vesicles.

Enterococcus spp. have been shown to have gastrointestinal tract protective functions; our recent results suggest that membrane vesicles (MVs) play an important role in the gastric protection of Enterococcus faecium (E. faecium). The specific function is determined by molecular compositions of MVs. To resolve biocargo components in E. faecium MVs (EfmMVs), MVs were isolated from E. faecium culture. Transcriptomics, label-free quantitative proteomics, and untargeted metabolomics were performed to obtain information about the complexity of ribonucleic acids (RNAs), proteins, and metabolites biocargo they carry, respectively. RNA-sequencing identified a total of 2122 transcripts. The top 20 transcripts accounted for 27.63% of total counts, which, including enzymes, participate in glycolysis, ribosomal proteins, DNA-directed RNA polymerases, protein-synthesizing relative enzymes, molecules associated with protein post-translational processing and transport, and peptidoglycan lyases. Label-free quantitative proteomics analysis identified a total of 711 proteins. The top 20 proteins accounted for 48.02% of all identified proteins, which including ribosomal proteins, enzymes participate in glycolysis, DNA-directed RNA polymerases, protein-synthesizing relative enzymes, peptidoglycan lyases, and autolysin. Untargeted metabolomics analysis identified a total of 519 metabolites. The top 20 metabolites accounted for 79.55% of all identified metabolites, which included amino acids, substrates, or products in the metabolism of amino acids, natural organic acids, products in the metabolism of organic acids, ketone compounds, and two other compounds. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that the identified biocargo components enriched in metabolism, genetic, and environmental information processing. Overall, we hope that the current exploration of multiple "-omics" analyses of this EfmMVs will provide useful information and further groundwork for future studies on E. faecium application.

Combined Mindfulness-Based Stress Reduction and Exercise Intervention for Improving Psychological Well-Being in Patients With Non-Small Cell Lung Cancer.

OBJECTIVE: This study aims to assess the clinical effectiveness of combining mindfulness-based stress reduction (MBSR) with exercise intervention in improving anxiety, depression, sleep quality and mood regulation in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 60 patients with NSCLC who had not received surgical treatment were selected using convenience sampling and divided into an intervention group and control group, with 30 patients in each group. The control group received conventional psychological nursing care, whereas the intervention group received a combination of MBwSR and exercise therapy. Before the intervention, a questionnaire was completed to collect the basic data of the two groups. Further questionnaires were administered at 6 and 8 weeks after treatment to assess anxiety, depression, sleep quality and other items included in the five-item Brief Symptom Rating Scale (BSRS-5). RESULTS: No significant differences between the intervention and control groups were identified in terms of personal and clinical characteristics (p > 0.05). No significant differences were determined in the BSRS-5, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) or Pittsburgh Sleep Quality Index (PSQI) scores between the intervention and control groups before the intervention. However, 6 and 8 weeks after the intervention, scores were significantly lower in both groups (p < 0.001). Significant differences in the BSRS-5, SAS, SDS and PSQI scores were identified between the two groups at different time points (p < 0.001). CONCLUSION: The combination of MBSR and exercise intervention demonstrated improvements in anxiety, depression, sleep quality and BSRS-5 scores in patients with NSCLC.

Self-Repairing Humidity-Adjustable Anisotropic Adhesion Switch for Smart Manipulation.

Stimuli-responsive surface adhesion regulation is widely used in automated assembly systems, intelligent pick-up and placement systems, and soft crawling robots. However, in the actual separation process, it tends to produce separation residue or excessive adhesion. Therefore, how to regulate surface adhesion on demand is a significant challenge. Herein, inspired by the anisotropic adhesion behavior of butterflies and the controlled adhesion behavior of octopuses, based on molecular conformational rearrangement and anisotropic structures, a humidity-responsive PES-PI/PDMS composite surface is achieved to meet the needs of controllable adhesion orientation and strength, which could be used for an intelligent transfer system (grasping and releasing and anisotropic transporting). Humidity can effectively tune the hydrogen bonding and the interaction between polymers, resulting in excellent self-healing and durability properties of the composite surface. Moreover, humidity could adjust the surface transmittance as well, making it possible to be used in humidity sensing and in a detection and encryption/decryption system to enhance environmental monitoring and information protection capabilities. This work not only establishes a method for the fabrication of innovative "high-flexibility" adhesive materials but also provides approaches for the design and development of intelligent response devices.

Whole-Exome Sequencing Identifies Germline BLM Mutation in Ovarian Hepatoid Adenocarcinoma with Favorable Response to Niraparib and Anlotinib Combination Therapy-A Case Report and Literature Review.

Hepatoid adenocarcinoma of the ovary represents a rare and malignant extrahepatic tumor that shares morphological and immunophenotypic similarities with hepatocellular carcinoma. Due to the ambiguous histomorphology and aggressive behavior, the diagnosis and management of hepatoid adenocarcinoma of the ovary present unique challenges. Here, we present a 67-year-old woman with massive ascites and disseminated peritoneal implants at initial diagnosis. She was treated with six cycles of neoadjuvant therapy (albumin-bound paclitaxel + nedaplatin + bevacizumab) and a debulking surgery, followed by eight cycles of postoperative adjuvant therapy (albumin-bound paclitaxel + carboplatin + bevacizumab). Elaborate pathology workup found significant involvement of angiogenesis in the tumor and confirmed the diagnosis via immunohistochemistry. Further molecular characterization of the tumor by whole-exome sequencing (WES) revealed a novel heterozygous germline mutation (NM_000057.2, c.1290_1291delinsATCAGGCCTCCATAG, p.Y430fs1) in gene BLM, likely pathogenic, suggesting a potential candidate for Poly (ADP-ribose) polymerase (PARP) inhibitors. For the maintenance therapy, she received a combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib. As of now, the patient has achieved a partial response, with no apparent evidence of disease progression observed nearly 30 months. Our study sheds light on the WES-based profiling in rare cancers to screen for any treatable targets with otherwise no standard therapeutic options. The promising results with the niraparib-anlotinib combination suggest its potential as a maintenance therapy option for hepatoid adenocarcinoma of the ovary, which warrants validation in future larger cohort.

Metabolomics reveals the lipid metabolism disorder in Pelophylax nigromaculatus exposed to environmentally relevant levels of microcystin-LR.

Cyanobacterial blooms have emerged as a significant environmental issue worldwide in recent decades. However, the toxic effects of microcystin-LR (MC-LR) on aquatic organisms, such as frogs, have remained poorly understood. In this study, frogs (Pelophylax nigromaculatus) were exposed to environmentally relevant concentrations of MC-LR (0, 1, and 10 µg/L) for 21 days. Subsequently, we assessed the impact of MC-LR on the histomorphology of the frogs' livers and conducted a global MS-based nontarget metabolomics analysis, followed by the determination of substances involved in lipid metabolism. Results showed that MC-LR significantly induced histological alterations in the frogs' hepatopancreas. Over 200 differentially expressed metabolites were identified, primarily enriched in lipid metabolism. Biochemical analysis further confirmed that MC-LR exposure led to a disorder in lipid metabolism in the frogs. This study laid the groundwork for a mechanistic understanding of MC-LR toxicity in frogs and potentially other aquatic organisms.

Celastrol reduces lung inflammation induced by multiwalled carbon nanotubes in mice via NF-κb-signaling pathway.

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.

Exploring regulatory network of icariin synthesis in Herba Epimedii through integrated omics analysis.

Herba Epimedii's leaves are highly valued in traditional Chinese medicine for their substantial concentration of flavonoids, which play a crucial role in manifesting the plant's therapeutic properties. This study investigated the metabolomic, transcriptomic and proteomic profiles of leaves from two Herba Epimedii cultivars, Epipremnum sagittatum (J) and Epipremnum pubescens (R), at three different developmental stages. Metabolite identification and analysis revealed a total of 1,412 and 1,421 metabolites with known structures were found. Flavonoids made up of 33%, including 10 significant accumulated icariin analogues. Transcriptomic analysis unveiled totally 41,644 differentially expressed genes (DEGs) containing five encoded genes participated in icariin biosynthesis pathways. Totally, 9,745 differentially expressed proteins (DEPs) were found, including Cluster-47248.2.p1 (UDP-glucuronosy/UDP-glucosyltransferase), Cluster-30441.2.p1 (O-glucosyltransferase), and Cluster-28344.9.p1 (anthocyanidin 3-O-glucoside 2 "-O-glucosyltransferase-like) through proteomics analysis which are involved to icariin biosynthesis. Protein-protein interaction (PPI) assay exhibited, totally 12 proteins showing a strong relationship of false discovery rate (FDR) <0.05 with these three proteins containing 2 leucine-rich repeat receptor kinase-like protein SRF7, and 5 methyl jasmonate esterase 1. Multi-omics connection networks uncovered 237 DEGs and 72 DEPs exhibited significant associations with the 10 icariin analogues. Overall, our integrated omics approach provides comprehensive insights into the regulatory network underlying icariin synthesis in Herba Epimedii, offering valuable resources for further research and development in medicinal plant cultivation and pharmaceutical applications.

[Effects of Different Forms of Nitrogen Addition on Soil Physical and Chemical Properties and Microbial Community Structure of Perennial Alpine Cultivated Grassland].

This study aimed to investigate the impact of different nitrogen forms on soil physicochemical properties and microbial community structure in perennial alpine cultivated grasslands, in order to provide scientific basis for developing nitrogen addition strategies for perennial alpine cultivated grasslands. In June 2022, a 4-year-old Qinghai grassland mixed with Poa pratensis Qinghai and Festuca sinensis Qinghai was established at the Bakatai Farm in Gonghe County, Hainan Tibetan Autonomous Prefecture, Qinghai Province. The study was conducted without fertilization as a control (CK), and three different forms of nitrogen treatments were set up, namely, U:urea (amide nitrogen), A:ammonium sulfate (ammonium nitrogen), and N:calcium nitrate (nitrate nitrogen); the nitrogen application rate for each treatment was 67.5 kg·(hm2·a)-1, and the composition and diversity of soil nutrients and microbial communities under different treatments were analyzed. The results showed that the input of exogenous ammonium nitrogen significantly increased NH4+-N content, AP content, and EC; amide nitrogen input significantly increased SOC content and TN content; and nitrate nitrogen input significantly increased NO3--N content, AN content, and TC content. Exogenous nitrogen input changed the structure of soil bacterial and fungal communities, as well as the relative abundance of dominant phyla and genera, but it did not significantly affect the alpha diversity of bacterial and fungal communities. Principal coordinate analysis (PCoA) showed that different forms of nitrogen addition had a significant impact on the Beta diversity of bacterial communities, whereas the impact on fungal communities was not significant. Redundancy analysis (RDA) indicated that nitrogen addition mainly changed the composition and structure of microbial communities through soil ammonium nitrogen. Overall, ammonium nitrogen fertilizer should be given priority in the soil remediation process of perennial cultivated grasslands in the Qinghai Tibet Plateau.

Clinicopathological characteristics and prognosis of synchronous brain metastases from non-small cell lung cancer compared with metachronous brain metastases.

Purpose: Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is a serious complication severely affecting patients' prognoses. We aimed to compare the clinicopathological features and prognosis of synchronous and metachronous BM from NSCLC. Methods: Clinical data of 461 patients with brain metastases from NSCLC who visited the Cancer Hospital of China Medical University from 2005 to 2017 were retrospectively collected. We analyzed the pathophysiological characteristics of synchronous and metachronous BM from NSCLC and survival rates of the patients. Propensity score matching analysis was used to reduce bias between groups. In addition, we used the Kaplan-Meier method for survival analysis, log-rank test to compare survival rates, and Cox proportional hazards regression model for multivariate prognosis analysis. Results: Among 461 patients with BM, the number of people who met the inclusion criteria was 400 cases, and after 1:2 propensity score matching,130 had synchronous BM and 260 had metachronous BM. The survival time was longer for metachronous BM in driver mutation-negative patients with squamous cell carcinoma than synchronous BM. Conversely, metachronous and synchronous BM with gene mutations and adenocarcinoma showed no differences in survival time. Multivariate analysis showed that metachronous BM was an independent prognostic factor for overall survival. Furthermore, the pathological type squamous cell carcinoma and Karnofsky Performance Status score <80 were independent risk factors affecting overall survival. Conclusion: BM status is an independent factor influencing patient outcome. Moreover, synchronous and metachronous BM from NSCLC differ in gene mutation profile, pathological type, and disease progression and hence require different treatments.

Drug Analysis of Voriconazole Combined with Granulocyte Colony Stimulating Factor.

BACKGROUND: The aim of the study was to improve the clinical cognition of leukemia-like reaction caused by voriconazole and granulocyte colony-stimulating factor and to avoid misdiagnosis or delayed diagnosis. METHODS: A case of drug analysis of Voriconazole combined with granulocyte colony stimulating factor was retrospectively analyzed and related literature was reviewed. RESULTS: Blood routine of the patient on July 29: WBC 13.48 x 109/L, neutrophil 85.3%, lymphocyte 13.4%, hemoglobin 111 g/L, platelet 285 x 109/L. Vancomycin was given to prevent intracranial infection. Lumbar puncture was performed on July 30, cerebrospinal fluid was sent for routine and biochemical examination, leukocytes were 0.15 x 109/L, monocytes 45%, polynuclear cells 55%, protein 1.172 g/L, Acinetobacter baumannii and Candida clorbicus were detected in sputum culture, vancomycin and meropenem static sites were given to prevent intracranial secondary infection. Fungi were detected in urine culture, and voriconazole was given to prevent fungal infection. Blood routine: White blood cell 0.61 x 109/L, neutrophil 23%, lymphocyte 73.8%, red blood cell 2.65 x 1012/L, hemoglobin 77 g/L, platelet 17 x 109/L, bone marrow was extracted after medication. Bone marrow images show poor myelodysplasia, with granulocytes dominated by protoearly cells. Subsequent flow cytometry, chromosomal karyotype, and fusion gene analysis were performed to exclude the possibility of leukemia. Flow cytometry showed that the proportion of myeloid primordial cells was not high, the granulocytes were mainly at the early and young stage, no abnormal phenotype was observed in erythrocytes, monocytes and NK cells, no obvious mature B lymphocytes were observed, and the ratio of CD4+/CD8+ was decreased. Karyotype results showed that there was no mitotic phase. The results of fusion gene analysis showed that the fusion gene was negative or lower than the detection sensitivity. Voliconazole was stopped first, and granulocyte colony stimulating factor was stopped 3 days later. Two weeks later, blood and bone marrow images basically recovered, white blood cell 7.88 x 109/L, neutrophil 46.3%, lymphocyte 48.2%, hemoglobin 126 g/L, platelet 142 x 109/L, bone marrow hyperplasia active. The proportion of three series is roughly normal. CONCLUSIONS: The reason for the occurrence of leukemia-like reaction in this patient was considered to be related to voriconazole and granulocyte colony stimulating factor, cessation of voriconazole and granulocyte colony stimulating factor, and recovery of blood and bone marrow images. In the clinical use of voriconazole and granulocyte colony stimulating factor, close attention should be paid to the drug interaction and individualized medication should be carried out to ensure the safety of medication.

Association between ideal cardiovascular health and abnormal glucose metabolism in the elderly: evidence based on real-world data.

BACKGROUND: Limited information is available on the effect of ideal cardiovascular health (CVH) and abnormal glucose metabolism in elderly people. We aimed to analyze the prevalence of CVH behaviors, abnormal glucose metabolism, and their correlation in 65 and older people. METHODS: In this study, randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used. Recruiting was carried out between January 2020 and December 2020, and 1984 participants aged 65 years or older completed the study. RESULTS: The prevalence of abnormal glucose metabolism in this group was 26.7% (n = 529), among which the prevalence of impaired fasting glucose (IFG) was 9.5% (male vs. female: 8.7% vs 10.1%, P = 0.338), and the prevalence of type 2 diabetes mellitus (T2DM) was 19.0% (male vs. female: 17.8 vs. 19.8%, P = 0.256). The ideal CVH rate (number of ideal CVH metrics ≥ 5) was only 21.0%. The risk of IFG and T2DM decreased by 23% and 20% with each increase in one ideal CVH metrics, with OR (95%CI) of 0.77(0.65-0.92) and 0.80(0.71-0.90), respectively (P -trend < 0.001). TyG fully mediated the ideal CVH and the incidence of T2DM, and its mediating effect OR (95%CI) was 0.88(0.84-0.91). CONCLUSIONS: Each increase in an ideal CVH measure may effectively reduce the risk of abnormal glucose metabolism by more than 20%.

Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 µg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 µg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.