Overview of extracellular vesicles in the pathogenesis of preeclampsia†.

Preeclampsia (PE) is a leading cause of maternal and fetal-neonatal deaths, and its pathogenesis has been linked to the involvement of extracellular vesicles (EVs). EVs are a heterogeneous group of cell-originated membranous vesicles including exosomes, microvesicles, and apoptotic bodies. EVs transport various bioactive cargos such as lipids, proteins, or nucleic acids, and thus mediate cellular communication and contribute to the proper functioning of cells, organs and processes, including normal pregnancy. Numerous studies have reported that EVs are associated with abnormal levels of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) in PE. EVs isolated from preeclamptic women have been implicated in trophoblast dysfunction and have been reported to activate endothelium, monocytes, and platelets, and to be involved in defective placentation, imbalanced angiogenesis, and intravascular inflammation. When injected into pregnant rodents, these EVs induced hypertension, proteinuria, and adverse fetal outcomes. Deciphering the contribution of EVs to PE will advance our current understanding of this disorder and may lead to more clinical strategies for the management of PE. Of note, the composition of EV cargos may be characteristic of the status and stages of gestation, providing researchers the possibility of one day using EVs as novel, noninvasive, biomarkers for early screening of PE. Herein, we reviewed the latest research into EVs with emphasis on their role in the pathogenesis of PE and their applications as biomarkers in the early screening of this pregnancy-specific disorder.

Acetylcholine ameliorated hypoxia-induced oxidative stress and apoptosis in trophoblast cells via p38 MAPK/NF-κB pathway.

Hypoxia-induced oxidative stress and apoptosis of trophoblast are involved in the pathogenesis of preeclampsia (PE). Extensive research reports that the principal vagal neurotransmitter acetylcholine (ACh) shows anti-oxidative and anti-apoptotic effects in various diseases models. However, the role of ACh in hypoxic trophoblast remains unknown. Here, we examined the apoptotic levels of human placenta and explored the role(s) of ACh on cobalt chloride (CoCl2)-treated (trophoblast-derived) HTR-8/SVneo cells for mimicking hypoxic injuries. Cell counting kit-8 (CCK-8), dihydroethidium (DHE) probe, western blotting, immunofluorescence staining, migration and invasion assay were employed in the current study. Our data showed that placentas from PE women exhibited increased level of reactive oxygen species (ROS) and apoptotic index than those in normal pregnancy. Our in vitro study showed that CoCl2 enhanced ROS generation and apoptosis in HTR-8/SVneo cells through the activation of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB) pathway. ACh significantly decreased hypoxia-induced ROS generation and the resulting apoptosis, accompanied by lowered phosphorylation of p38 MAPK and NF-κB. Western blotting analysis further confirmed that ACh decreased the ratio of pp38 MAPK/p38 MAPK, p-NF-κB/NF-κB, Bax/Bcl-2 and cleaved Caspase-3/Caspase-3. Besides, ACh promoted cell invasion and migration ability under hypoxic conditions. Atropine, the muscarinic receptor antagonist, abolished ACh's effects mentioned above. Overall, our data showed that ACh exerted protective effects on hypoxia-induced oxidative stress and apoptosis in trophoblast cells via muscarinic receptors, indicating that improved vagal activity may be of therapeutic value in PE management.

Acetylcholine ameliorated TNF-α-induced primary trophoblast malfunction via muscarinic receptors†.

Oxidative stress and apoptosis of trophoblasts are involved in preeclampsia (PE). Numerous studies have shown that acetylcholine (ACh), the principal vagal neurotransmitter, plays a crucial role in attenuating oxidative stress, inflammation, and apoptosis in a variety of human diseases. However, the role of ACh in PE management remains unclear. Here, we aimed to determine the effects of ACh on TNF-α-treated human primary trophoblast cells. Western blotting, CCK-8, DHE, TUNEL immunofluorescence staining, transwell assays, and wound-healing assays were performed to evaluate the role of ACh in vitro. We found that both TNF-α expression and the apoptotic index were higher in placentas from preeclamptic women than in normal placentas. TNF-α enhanced oxidative stress and increased the number of TUNEL-positive nuclei, Bax/Bcl-2 ratio, and the cleaved caspase-3/caspase-3 ratio while decreasing cell viability in primary human trophoblast cells. TNF-α promoted cell migration and invasion. PDTC, a selective NF-κB inhibitor, significantly blunted TNF-α-induced effects. ACh treatment attenuated oxidative stress and apoptosis while further promoting migration and invasion of TNF-α-treated primary trophoblast cells. The effects of ACh could be reversed by the muscarinic receptor antagonist atropine. Overall, our findings indicate that ACh significantly ameliorates TNF-α-induced oxidative stress and apoptosis of human primary trophoblast cells via muscarinic receptors. This is the first time that the improvement of vagal activity served as a therapeutic strategy for PE-like trophoblasts, suggesting its potential value in clinical practice.

Whole exome and target sequencing identifies MAP2K5 as novel susceptibility gene for familial non-medullary thyroid carcinoma.

Although the genotype-phenotype for familial medullary thyroid carcinoma (FMTC) is well studied, only few low susceptibility risk loci were identified for familial non-medullary thyroid carcinoma (FNMTC). The aim of this study is to screen and identify high-penetrate genes for FNMTC. A total of 34 families with more than two first-degree relatives diagnosed as papillary thyroid cancer without other familial syndrome were recruited. Whole exome and target gene sequencing were performed for candidate variants. These variants were screened and analyzed with ESP6500, ExAC, 1000 genomes project, and the Cancer Genome Atlas (TCGA) with SIFT score and Polyphen2 prediction. Finally, we identified recurrent genetic mutation of MAP2K5 variants c.G961A and c.T1100C (p. A321T and p.M367 T) as susceptibility loci for FNMTC. The frequencies of MAP2K5 c.G961A and c.T1100C were found, 0.0385 and 0.0259 in FNMTC and 0 and 0.00022523 in healthy Chinese controls (n = 2200, P < 0.001), respectively. Both variants were located in the protein kinase domain. The functional study showed that MAP2K5 A321T or M367 T could consistently phosphorylate downstream protein ERK5 on site Ser731 + Thr733 or Ser496, promoting nuclear translocation and subsequently altering target gene expressions. Our data revealed that MAP2K5 variants A321T or M367 T can activate MAP2K5-ERK5 pathway, alter downstream gene expression, and subsequently induce thyroid epithelial cell malignant transformation. While classic MAP2K1/2(MEK1/2)-ERK1/2 signaling is well known for driving sporadic NMTC, our research indicated that MAP2K5 (MEK5) is a susceptibility gene for FNMTC. These findings highlight the potential application of MAP2K5 for molecular diagnosis as well as early prevention.

Gclc deficiency in mouse CNS causes mitochondrial damage and neurodegeneration.

Gamma glutamyl cysteine ligase (GCL) is the rate-limiting enzyme for intracellular glutathione (GSH) synthesis. The GSH concentration and GCL activity are declining with age in the central nervous system (CNS), and is accompanied by elevated reactive oxygen species (ROS). To study the biological effects of low GSH levels, we disrupted its synthesis both at birth by breeding a Gclc loxP mouse with a thy1-cre mouse (NEGSKO mouse) and at a later age by breeding with a CaMKII-ERT2-Cre (FIGSKO mouse). NEGSKO mice with deficiency of the Gclc in their entire CNS neuronal cells develop at 4 weeks: progressive motor neuron loss, gait problems, muscle denervation and atrophy, paralysis, and have diminished life expectancy. The observed neurodegeneration in Gclc deficiency is of more chronic rather than acute nature as demonstrated by Gclc targeted single-neuron labeling from the inducible Cre-mediated knockout (SLICK) mice. FIGSKO mice with inducible Gclc deficiency in the forebrain at 23 weeks after tamoxifen induction demonstrate profound brain atrophy, elevated astrogliosis and neurodegeneration, particularly in the hippocampus region. FIGSKO mice also develop cognitive abnormalities, i.e. learning impairment and nesting behaviors based on passive avoidance, T-Maze, and nesting behavior tests. Mechanistic studies show that impaired mitochondrial glutathione homeostasis and subsequent mitochondrial dysfunction are responsible for neuronal cell loss. This was confirmed by mitochondrial electron transporter chain activity analysis and transmission electron microscopy that demonstrate remarkable impairment of state 3 respiratory activity, impaired complex IV function, and mitochondrial swollen morphology in the hippocampus and cerebral cortex. These mouse genetic tools of oxidative stress open new insights into potential pharmacological control of apoptotic signaling pathways triggered by mitochondrial dysfunction.

Trends in and correlations between antibiotic consumption and resistance of Staphylococcus aureus at a tertiary hospital in China before and after introduction of an antimicrobial stewardship programme.

The overuse of antibiotics and the rapid emergence of antibiotic resistance prompted the launch of an antimicrobial stewardship programme in 2011. This study aimed to investigate the trends and correlations between antibiotic consumption and resistance of Staphylococcus aureus in a tertiary hospital of northwest China from 2010 to 2016. Trends were analysed by linear regression, and correlations were assessed by an autoregressive integrated moving average model. The total consumption of antibiotics halved during the 7-year study period, while the rates of resistance of S. aureus decreased significantly or remained stable; methicillin-resistant S. aureus (MRSA) declined markedly, from 73.3% at the beginning of the study to 41.4% by the end. This latter decrease was significantly correlated with the consumption of several classes of antibiotics. In conclusion, reduction in antibiotic use impacted significantly on resistance rates and contributed to a decline in MRSA prevalence.

Granulocyte-macrophage colony-stimulating factor increases tumor growth and angiogenesis directly by promoting endothelial cell function and indirectly by enhancing the mobilization and recruitment of proangiogenic granulocytes.

Granulocyte-macrophage colony-stimulating factor has been widely used as an adjuvant therapy for cancer patients exhibiting myelosuppression induced by chemotherapy or radiotherapy. However, the effects of granulocyte-macrophage colony-stimulating factor on tumor growth, as well as its precise mechanism, are still controversial due to inconsistent evidence. This study investigated the effect of exogenous granulocyte-macrophage colony-stimulating factor on the growth of B16 melanoma, S180 sarcoma, and U14 cervical carcinoma in mice. The angiogenesis and recruitment of bone-marrow-derived cells were analyzed in tumor tissues. Interactions among granulocyte-macrophage colony-stimulating factor, bone-marrow-derived cells, and B16 tumor cells were investigated in vitro. Proangiogenic types of bone-marrow-derived cells in blood were assessed both in vivo and in vitro. The results showed that granulocyte-macrophage colony-stimulating factor markedly facilitated the growth of B16 and S180 tumors, but not U14 tumors. Granulocyte-macrophage colony-stimulating factor increased the densities of blood vessels and the number of bone-marrow-derived cells in B16 tumor tissues. The granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor cell proliferation was mediated by bone-marrow-derived cells in vitro. Meanwhile, a distinct synergistic effect on endothelial cell function between granulocyte-macrophage colony-stimulating factor and bone-marrow-derived cells was observed. After separating two types of bone-marrow-derived cells, granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor growth and angiogenesis in vivo was mediated by proangiogenic cells in granulocytes, but not monocytes, with CD11b+, vascular endothelial growth factor receptor 2, and C-X-C chemokine receptor 4 granulocytes possibly involved. These data suggest that granulocyte-macrophage colony-stimulating factor contributes to the growth and angiogenesis of certain types of tumor, and these mechanisms are probably mediated by proangiogenic cells in granulocytes. Applying granulocyte-macrophage colony-stimulating factor may attenuate the antitumor effects of chemotherapy and radiotherapy in certain types of tumor.

Meta-analysis of Comparison of the Newer P2Y12 Inhibitors (Oral Preparation or Intravenous) to Clopidogrel in Patients With Acute Coronary Syndrome.

AIMS: New P2Y12 adenosine diphosphate receptor antagonists have been used in the treatment of acute coronary syndrome (ACS) with different results. This systematic review analyzed and compared the evidence from large, clinical trials regarding the efficacy of clopidogrel relative to that of cangrelor, prasugrel, and ticagrelor in reducing the incidence of cardiovascular events in patients with ACS. METHODS AND RESULTS: This analysis compared newer P2Y12 inhibitors with clopidogrel of 13 clinical trials involved a total of 87,985 patients with ACS. The newer P2Y12 inhibitors include cangrelor, prasugrel, and ticagrelor. Newer P2Y12 inhibitors significantly decreased the risk of myocardial infarction and showed a trend toward reduction of cardiovascular death (odds ratio [OR] = 0.86, 95% confidence interval [CI], 0.77-0.96, and I = 54%, P < 0.05); (OR = 0.85, 95% CI, 0.77-0.93, and I = 42%, P < 0.001). The rates of stroke events and the incidence in patients with ACS did not differ statistically between the clopidogrel group and the group with newer P2Y12 inhibitors (OR = 0.95, 95% CI, 0.79-1.14, and I = 0%, P = 0.57). However, newer P2Y12 inhibitors showed a significant increase in thrombosis in MI major or minor bleeding (OR = 1.21, 95% CI, 1.03-1.42, and I = 56%, P = 0.02) compared with clopidogrel. CONCLUSIONS: Based on this meta-analysis, newer P2Y12 inhibitors were significantly more effective than clopidogrel in the events of myocardial infarction and cardiovascular death in patients with ACS, although the incidence of thrombosis in MI-defined bleeding was higher compared with clopidogrel.

ß3 phosphorylation of platelet αIIbß3 is crucial for stability of arterial thrombus and microparticle formation in vivo.

BACKGROUND: It is well accepted that functional activity of platelet integrin αIIbß3 is crucial for hemostasis and thrombosis. The ß3 subunit of the complex undergoes tyrosine phosphorylation shown to be critical for outside-in integrin signaling and platelet clot retraction ex vivo. However, the role of this important signaling event in other aspects of prothrombotic platelet function is unknown. METHOD: Here, we assess the role of ß3 tyrosine phosphorylation in platelet function regulation with a knock-in mouse strain, where two ß3 cytoplasmic tyrosines are mutated to phenylalanine (DiYF). We employed platelet transfusion technique and intravital microscopy for observing the cellular events involved in specific steps of thrombus growth to investigate in detail the role of ß3 tyrosine phosphorylation in arterial thrombosis in vivo. RESULTS: Upon injury, DiYF mice exhibited delayed arterial occlusion and unstable thrombus formation. The mean thrombus volume in DiYF mice formed on collagen was only 50% of that in WT. This effect was attributed to DiYF platelets but not to other blood cells and endothelium, which also carry these mutations. Transfusion of isolated DiYF but not WT platelets into irradiated WT mice resulted in reversal of the thrombotic phenotype and significantly prolonged blood vessel occlusion times. DiYF platelets exhibited reduced adhesion to collagen under in vitro shear conditions compared to WT platelets. Decreased platelet microparticle release after activation, both in vitro and in vivo, were observed in DiYF mice compared to WT mice. CONCLUSION: ß3 tyrosine phosphorylation of platelet αIIbß3 regulates both platelet pro-thrombotic activity and the formation of a stable platelet thrombus, as well as arterial microparticle release.

3D compressive spectral integral imaging.

A novel compressive 3D imaging spectrometer based on the coded aperture snapshot spectral imager (CASSI) is proposed. By inserting a microlens array (MLA) into the CASSI system, one can capture spectral data of 3D objects in a single snapshot without requiring 3D scanning. The 3D spatio-spectral sensing phenomena is modelled by computational integral imaging in tandem with compressive coded aperture spectral imaging. A set of focal stack images is reconstructed from a single compressive measurement, and presented as images focused on different depth planes where the objects are located. The proposed optical system is demonstrated with simulations and experimental results.

Evaluation of adverse health risks associated with antineoplastic drug exposure in nurses at two Chinese hospitals: The effects of implementing a pharmacy intravenous admixture service.

OBJECTIVE: To determine the health risks of antineoplastic drugs (ADs) occupational exposure in nurses and to evaluate the effects of implementing a pharmacy intravenous admixture service (PIVAS) in two Chinese hospitals. METHODS: The laboratory findings were collected from annual staff physical examination data. Reproductive toxicity and clinical manifestations were self-reported via a questionnaire. RESULTS: Hematotoxicity, organ damage, reproductive toxicity, and clinical manifestations associated with AD exposure were markedly higher in oncology nurses than unexposed nurses. Application of PIVAS led to a significant restoration of the blood cell counts and kidney function, and a reduction in adverse reproductive outcomes among oncology nurses. Pronounced symptoms related to AD exposure were alleviated as well. CONCLUSION: Oncology nurses who work with AD's experienced more adverse health outcomes than unexposed nurses. The health risks to AD were significantly alleviated by implementing a pharmacy intravenous admixture service.

Vasorelaxant activities of Danhong injection and their differential effects on the rat abdominal aorta and mesenteric artery.

Previous studies have found that Danhong injection (DHI), an extensively used herbal extract preparation in China, might be a powerful vasodilator. The aims of this study were to determine the vascular activity of DHI and its effects on arteries of different sizes. The results showed that DHI significantly inhibited rat-hindquarters and rabbit-ear vasoconstriction elicited by norepinephrine (NE) perfusion and markedly relaxed KCl-contracted and NE-contracted rat abdominal aortic and mesenteric artery rings. The endothelium made only a minor contribution to the vasorelaxant effect of DHI on artery segments. The vasorelaxant effect of DHI varied with the artery size, with larger arteries exhibiting a more sensitive and potent vasodilator response. DHI relaxed NE-induced vasoconstriction probably through inhibition of the intracellular Ca2+ release through the inositol triphosphate receptor system in the abdominal aorta and mesenteric artery, along with blockage of extracellular Ca2+ influx through the receptor-linked Ca2+ channels in the mesenteric artery. In addition, DHI completely relaxed KCl-induced contraction in both of the arteries, suggesting that inhibition of Ca2+ influx through voltage-gated Ca2+ channels is involved in the vasorelaxant effect of DHI. This elucidation of the vascular effects of DHI and the underlying mechanisms could lead to improved clinical applications.

Highly selective screening of the bioactive compounds in Huoxue capsule using immobilized ß(2)-adrenoceptor affinity chromatography.

A highly selective assay was developed for screening compounds that bind to the porcine recombinant ß2-adrenoceptor (ß2-AR) with affinity chromatography coupled to quadrupole time-of-flight mass spectrometry (Q-TOF-MS). The methodology involved selective screening with immobilized ß2-AR, a highly accurate identification via Q-TOF-MS, and a functional evaluation of the screened compounds with a sensitive myograph system. Ferulic acid, hydroxysafflor yellow A (HSYA), and naringin were confirmed to be the bioactive compounds in Huoxue capsule that specifically bound to the ß2-AR. These compounds produced a concentration-dependent relaxation of arteries that were contracted by treatment with phenylephrine, and the relaxation caused by these compounds was attenuated in the presence of ICI 118551, a type of ß2-AR antagonist. Our data indicate that the use of an immobilized receptor is potentially an alternative method for the rapid screening of bioactive compounds in a complex matrix because of its high specificity. ß2-AR affinity chromatography was valuable in focusing attention on the further investigation of ferulic acid, HSYA, and naringin as ß2-AR agonists.

Dose-dependent bidirectional pharmacological effects of vinorelbine-based metronomic combination chemotherapy on tumor growth and metastasis and mechanisms in melanoma mouse model.

BACKGROUND: There is evidence that the empirical setting of doses and schedules of antineoplastic agents in metronomic chemotherapy (MC) might lead to undesirable outcomes, such as promoting tumor growth or metastasis at certain low doses. However, details about the dose effect of antineoplastic agents in MC have not been fully known yet. OBJECTIVES: Vinorelbine combined with cisplatin or fluorouracil (VNR/CDDP or VNR/FU) was selected to investigate its effects on tumor growth or metastasis as well as mechanisms. METHODS: Experimental techniques, including immunohistochemistry, western blot, immunofluorescence, and flow cytometry, were used to explore the mechanisms, along with cell proliferation, apoptosis, migration, and invasion. RESULTS: The results showed that VNR/CDDP or VNR/FU promoted tumor growth and metastasis at low doses and inhibited them at high ones. Except that expressions of apoptotic proteins were elevated at both low and high doses, low-dose treatments enhanced angiogenesis and promoted the mobilization and recruitment of myeloid-derived suppressor cells (MDSCs), while high-dose treatments reversed these effects. Additionally, low concentrations of VNR/CDDP or VNR/FU stimulated tumor cell functions such as anti-apoptosis, migration, and invasion, but high concentrations only suppressed cell proliferation and increased apoptosis. CONCLUSION: This study elucidated a bidirectional action mode regulated by multiple mechanisms at different doses in MC and also highlighted the risks of low-dose metronomic administration of antineoplastic agents in the clinic. More preclinical and clinical studies focusing on the dose-effect of metronomic regimens are urgently needed because an effective therapeutic regimen should be an optimal setting of drugs, doses, schedules, or combinations.

Dual­directional effect of vinorelbine combined with cisplatin or fluorouracil on tumor growth and metastasis in metronomic chemotherapy in breast cancer.

Metronomic chemotherapy (MCT) regimens may be associated with risks to the patient due to the ambiguity surrounding low dosages and schedules. In the present study, metronomic regimens of vinorelbine (NVB) combined with cisplatin (CDDP) or fluorouracil (5­FU) were chosen to study the dose­response associations with tumor growth and metastasis, along with the underlying mechanisms in angiogenesis, apoptosis and tumor immunity, using experimental techniques such as immunofluorescence, immunohistochemistry, western blotting and flow cytometry. The results demonstrated a dual­directional pharmacological action of promoting and suppressing tumor growth or metastasis in BALB/c mice bearing a 4T1 tumor at certain low and high doses of the drugs. Low doses of NVB combined with CDDP or 5­FU accelerated tumor growth by enhancing angiogenesis, increasing the expression of angiogenic proteins, NF­κB and osteopontin in tumor tissues, and inducing the accumulation of myeloid­derived suppressor cells and macrophages. By contrast, higher doses inhibited tumor growth by suppressing these effects. Notably, the upregulation of apoptotic proteins was observed after low­ and high­dose treatments. Furthermore, at low concentrations, NVB combined with CDDP or 5­FU stimulated certain functions of endothelial and tumor cells, including migration and invasion, whereas at higher concentrations they suppressed proliferation and induced apoptosis. Therefore, the results of the present study suggested the potential risks of metronomic combination chemotherapy by demonstrating that, at certain low doses, tumor growth or metastasis was promoted, and emphasized the existence of an effective dose interval that changes with different drug combinations. However, further studies are needed before a specific metronomic combination regimen can be administered clinically for cancer treatment.

The dynamic equilibrium between the protective and toxic effects of matrine in the development of liver injury: a systematic review and meta-analysis.

Background: Matrine, an alkaloid derived from the dried roots of Sophora flavescens Aiton, has been utilized for the treatment of liver diseases, but its potential hepatotoxicity raises concerns. However, the precise condition and mechanism of action of matrine on the liver remain inconclusive. Therefore, the objective of this systematic review and meta-analysis is to comprehensively evaluate both the hepatoprotective and hepatotoxic effects of matrine and provide therapeutic guidance based on the findings. Methods: The meta-analysis systematically searched relevant preclinical literature up to May 2023 from eight databases, including PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, WanFang Med Online, China Science and Technology Journal Database, and China Biomedical Literature Service System. The CAMARADES system assessed the quality and bias of the evidence. Statistical analysis was conducted using STATA, which included the use of 3D maps and radar charts to display the effects of matrine dosage and frequency on hepatoprotection and hepatotoxicity. Results: After a thorough screening, 24 studies involving 657 rodents were selected for inclusion. The results demonstrate that matrine has bidirectional effects on ALT and AST levels, and it also regulates SOD, MDA, serum TG, serum TC, IL-6, TNF-α, and CAT levels. Based on our comprehensive three-dimensional analysis, the optimal bidirectional effective dosage of matrine ranges from 10 to 69.1 mg/kg. However, at a dose of 20-30 mg/kg/d for 0.02-0.86 weeks, it demonstrated high liver protection and low toxicity. The molecular docking analysis revealed the interaction between MT and SERCA as well as SREBP-SCAP complexes. Matrine could alter Ca2+ homeostasis in liver injury via multiple pathways, including the SREBP1c/SCAP, Notch/RBP-J/HES1, IκK/NF-κB, and Cul3/Rbx1/Keap1/Nrf2. Conclusion: Matrine has bidirectional effects on the liver at doses ranging from 10 to 69.1 mg/kg by influencing Ca2+ homeostasis in the cytoplasm, endoplasmic reticulum, Golgi apparatus, and mitochondria. Systematic review registration: https://inplasy.com/, identifier INPLASY202340114.

Association between coffee and caffeine intake and risk of COPD: Findings based on NHANES 2007-2012.

BACKGROUND: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. OBJECTIVES: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012. METHODS: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. RESULTS: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. CONCLUSIONS: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms.

Safety and efficacy of magnesium-rich artificial cerebrospinal fluid for subarachnoid hemorrhage.

Objectives: This study aimed to investigate the efficacy of using a newly formulated magnesium-rich artificial cerebrospinal fluid (MACSF) as an alternative to normal saline (NS) for intraoperative irrigation during aneurysm clipping in improving the prognosis of patients with Aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with aSAH who underwent intraoperative irrigation with MACSF or NS during the clipping in the First Affiliated Hospital of Xi 'an Jiaotong University from March 2019 to March 2022 were selected as MACSF group and NS group, respectively. The primary prognostic indicators were the incidence of favorable outcomes (mRS 0-2). The secondary outcome measures included cerebral vasospasm (CVS), mortality, total hospital stay, and intensive care unit (ICU) stay. Safety was evaluated based on the occurrence rates of hypermagnesemia, meningitis, and hydrocephalus. Results: Overall, 34 and 37 patients were enrolled in the MACSF and NS groups, respectively. At 90 days after aSAH onset, the proportion of favorable prognosis in the MACSF group was significantly higher than that in the NS group (p = 0.035). The incidence of CVS within 14 days after surgery was significantly lower in the MACSF group than that in the NS group (p = 0.026). The mortality rate in the MACSF group was significantly lower than in the NS group (p = 0.048). The median lengths of hospital stay (p = 0.008) and ICU stay (p = 0.018) were significantly shorter in the MACSF group than in the NS group. No significant differences were observed in safety measures. Conclusion: Using MACSF as an irrigation fluid for aneurysm clipping can significantly improve the 90-day prognosis of patients with aSAH, which may be related to the reduced incidence of CVS. Clinical trial registration: https://www.clinicaltrials.gov, identifier NCT04358445.

A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing.

Angiogenesis alleviates hypoxic stress in ischemic tissues or during tumor progression. In addition to endothelial cell proliferation and migration, the angiogenic process requires bone marrow-derived cell (BMDC) recruitment to sites of neovascularization. However, the mechanism of communication between hypoxic tissues and the BM remains unknown. Using 2 models of hypoxia-induced angiogenesis (ischemic hindlimb surgery and subcutaneous tumor growth), we show that platelet infusion promotes BMDC mobilization into the circulation, BMDC recruitment into growing neovasculature, tumor vascularization, and blood flow restoration in ischemic limbs, whereas platelet depletion inhibits these effects. Thus, platelets are required for BMDC recruitment into ischemia-induced vasculature. Secretion of platelet α-granules, but neither dense granules nor platelet aggregation is crucial for BMDC homing and subsequent angiogenesis, as determined using VAMP-8(-/-), Pearl, and integrin Beta 3(-/-) platelets. Finally, platelets sequester tumor-derived promoters of angiogenesis and BMDC mobilization, which are counterbalanced by the antiangiogenic factor thrombospondin-1. A lack of thrombospondin-1 in platelets leads to an imbalance in proangiogenic and antiangiogenic factors and accelerates tumor growth and vascularization. Our data demonstrate that platelets stimulate BMDC homing in a VAMP-8-dependent manner, revealing a previously unknown role for platelets as key mediators between hypoxic tissues and the bone marrow during angiogenesis.

[An information extraction method of spectral images based on 3D spectral angle statistics].

A novel information extraction method of spectral images based on 3D spectral angle statistics is proposed. By computing the spectral angle between adjacent pixels of the image in the horizontal, vertical and diagonal direction respectively, a 3D information statistical model was then constructed. This model reflects the similarity between adjacent pixels which represent some kind of materials. Uniform areas and edge information of the same material, which will be used for the training sample collection in supervised classification, can be extracted from the image if different threshold values are set and slices are extracted from different axes in the statistical model. Compared with the traditional statistical tools, such as the histogram and scatter diagram, this statistical method has higher robustness and reliability. And it can obtain more information extracted from the spectral images.