Prognosis of patients with coexisting obesity and malnutrition after ischemic stroke: A cohort study.

BACKGROUND: The double burden of malnutrition, defined as the coexistence of obesity and malnutrition, is an increasing global health concern and is unclear in patients after ischemic stroke. The current study explored the combined impacts of obesity and malnutrition on patients with ischemic stroke. METHODS: We conducted a single-center prospective cohort study with patients with ischemic stroke enrolled in Minhang Hospital in China between January 2018 and December 2022. Patients were stratified into four categories based on their obesity (defined by body mass index) and nutritional status (classified according to the Controlling Nutritional Status score): (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. The primary end points were poor outcomes and all-cause mortality at 3 months. RESULTS: A total of 3160 participants with ischemic stroke were included in our study, of which 64.7% were male and the mean age was 69 years. Over 50% of patients were malnourished. At 3-month follow-up, the malnourished nonobese had the worst outcomes (34.4%), followed by the malnourished obese (33.2%), nourished nonobese (25.1%), and nourished obese (21.8%; P < 0.001). In multivariable analyses, with nourished nonobese group as the reference, the malnourished nonobese group displayed poorer outcomes (odds ratio [OR], 1.395 [95% CI, 1.169-1.664], P < 0.001) and higher all-cause mortality (OR, 1.541 [95% CI, 1.054-2.253], P = 0.026), but only a nonsignificant increase in poor prognosis rate (33.2% vs. 25.1%, P = 0.102) and mortality (4.2% vs. 3.6%, P = 0.902) were observed in the malnourished obese group. CONCLUSION: A high prevalence of malnutrition is observed in the large population suffering from ischemic attack, even in the obese. Malnourished patients have the worst prognosis particularly in those with severe nutritional status regardless of obesity, while the best functional outcomes and the lowest mortality are demonstrated in nourished obese participants.

High serum lactate dehydrogenase to albumin ratio is associated with increased risk of poor prognosis after ischemic stroke.

BACKGROUND: Lactate dehydrogenase to albumin ratio (LAR) is a comprehensive biomarker for anaerobiosis, inflammation, and nutritional status, but its prognostic value for ischemic stroke has rarely been reported. We aimed to prospectively investigate whether serum LAR is associated with the prognosis of ischemic stroke patients in a large-scale cohort study. MATERIALS AND METHODS: Serum LAR levels were measured among 6634 patients with ischemic stroke admitted at Minhang hospital from January 2018 to December 2022. The primary outcome was the composite of major disability and death (modified Rankin Scale score [mRS] ≥ 3) at 3-month follow up. Secondary outcomes included death and the ordered 7-level category score of mRS. Multivariate logistic regression and restricted cubic splines were adopted to evaluate the associations between serum LAR levels and adverse clinical outcomes of ischemic stroke. RESULTS: During 3 months of follow-up period, a total of 2125 patients experienced primary outcome. After multivariate adjustment, the highest quartile of serum LAR was associated with an increased risk of primary outcome (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.27-1.83; P for trend < 0.001). Each standard deviation higher log-transformed serum LAR resulted in a 20% (95% CI, 12%-28%) increased risk of primary outcome. Furthermore, multivariable-adjusted restricted cubic spline analyses showed a linear association between the serum LAR level with primary outcome (P for linearity < 0.001). Finally, the addition of serum LAR to conventional risk factors significantly improved risk predictive abilities for the primary outcome (net reclassification improvement [NRI]: 18.35%, P < 0.001; integrated discrimination improvement [IDI]: 0.35%, P < 0.001) at 3-month follow up in patients with ischemic stroke. CONCLUSION: High serum LAR level was independently associated with an increased risk of adverse clinical outcomes among patients with ischemic stroke, indicating that serum LAR may be a valuable prognostic biomarker for ischemic stroke.

Mapping knowledge domains on managerial overconfidence.

Managerial overconfidence issues have attracted extant research interest given its influence on corporate strategy and operating performance with the growing development of modern behavioural economics. In this paper, bibliometric tools of VOSviewer and CiteSpace are used to reflect the research trend, hot spots and evolving route of managerial overconfidence theme. The publishing and citation numbers of managerial overconfidence paper are experiencing an overall increasing trend from 1992 to 2021. We sum up the top source journal, institutions, countries and the top 10 highly cited papers, and 272 keywords are distributed in the occurrence graph related to the theme of managerial overconfidence. Twelve keyword clusters from individual, organisational and social levels are identified. The research span is divided into four periods: preliminary, exploratory, growth and outbreak periods, and important research hot spots are summed up with highly cited keywords. The extant literature measurement and variables of managerial overconfidence are summarised in four types, and the integrated research frame of managerial overconfidence is proposed. Future research expansion of managerial overconfidence can be carried out from five aspects of harmony classification, improved measurement, multivariate test, positive paradigm and cultural distinction.

Preconditioned MSCs Alleviate Cerebral Ischemia-Reperfusion Injury in Rats by Improving the Neurological Function and the Inhibition of Apoptosis.

Mesenchymal stem cells (MSCs) have great application prospects in the treatment of ischemic injury. However, their long-time cultivation before transplantation and poor survival after transplantation greatly limit the therapeutic effect and applications. This study aimed to investigate whether MSCs under the ischemic microenvironment could improve their survival and better alleviate cerebral ischemic injury. Firstly, we used ischemic brain tissue to culture MSCs and evaluated the functional changes of MSCs. Then a middle cerebral artery occlusion (MCAO) model was induced in rats, and the pretreated MSCs were injected via the tail vein. The adhesive removal test, rotarod test, modified neurological severity score, and pathological analyses were applied to assess the rats' neurological function. Then the expression of neuron and apoptosis related markers was detected. The results indicated that ischemic brain tissue pretreated MSCs promoted the proliferation and the release of the growth factors of MSCs. Meanwhile, in MCAO model rats, transplantation of pretreated MSCs enhanced the neurogenesis, attenuated behavioral changes, reduced infarct size, and inhibited apoptosis. The expression of B-cell lymphoma-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), NF-L, and NeuN were increased, while BCL2-Associated X (Bax) and Caspase-3 decreased. Our results suggest that MSCs pretreatment with stroke brain tissue could be an effective strategy in treating cerebral ischemic injury.

CYP4 subfamily V member 2 (CYP4V2) polymorphisms were associated with ischemic stroke in Chinese Han population.

BACKGROUND: CYP4 subfamily V member 2 (CYP4V2) polymorphisms are related to venous thromboembolism. However, the influence of CYP4V2 polymorphisms on the susceptibility to ischemic stroke (IS) remains undetermined. METHODS: We selected and genotyped five polymorphisms of CYP4V2 in 575 cases and 575 controls to test whether CYP4V2 variants were associated with the risk for IS in a Chinese Han population. Genotyping of CYP4V2 polymorphisms was performed using the Agena MassARRAY platform. Logistic regression analysis was used to assess the association between CYP4V2 polymorphisms and IS risk by calculating odds ratios (ORs) and 95% confidence interval (CI). False-positive report probability analysis was applied to assess the noteworthy relationship of the significant findings. RESULTS: CYP4V2 rs1398007 might be a risk factor for IS (OR = 1.34, 95% CI 1.05-1.71, p = 0.009). Specially, confounding factors (age, gender, smoking and drinking status) might affect the relationship between rs1398007 and IS susceptibility. Moreover, rs1053094 and rs56413992 were associated with IS risk in males. Multifactor dimensionality reduction analysis showed the combination of rs13146272 and rs3736455 had the strongest interaction effect (information gain value of 0.40%). Furthermore, genotypes of rs1398007 (p = 0.006) and rs1053094 (p = 0.044) were associated with the levels of high-density lipoprotein cholesterol (HDL-C) among healthy controls. CONCLUSION: Our results first provided evidence that CYP4V2 rs1398007 might be a risk factor for IS, which provides instructive clues for studying the mechanisms of CYP4V2 to the pathogenesis of IS.

Aluminum Trichloride Disorders Bile Acid Secretion and Induces Hepatocyte Apoptosis in Rats.

The aim of this study was to examine effects of aluminum trichloride (AlCl3) on the bile acid secretion and hepatocyte apoptosis in rats. Forty male Wistar rats (5 weeks old) weighed 110-120 g were orally exposed to AlCl3 at doses of 0, 64.18 (1/20LD50), 128.36 (1/10LD50), and 256.72 (1/5LD50) mg/kg body weight in drinking water for 120 days. Each group had ten rats. The serum total bile acid (TBA) concentration, the early and total hepatocyte apoptosis indexes, and protein and mRNA expression of Bcl-2 and Bax were determined. The results showed that the serum TBA concentration, the early and total hepatocyte apoptosis indexes, and protein and mRNA expression of Bax increased, while protein and mRNA expression of Bcl-2 decreased in AlCl3-treated rats. The results indicate that AlCl3 disorders bile acid secretion and induces hepatocyte apoptosis in rats.

Effects of Al on the splenic immune function and NE in rats.

Norepinephrine (NE) regulates the splenic immune function and it may be related to the effects of Aluminum (Al) on the splenic immune function. Here, the aim of this study was to further explore the effects of aluminum trichloride (AlCl3) on the splenic immune function and its relationship with NE. Forty male Wistar rats were orally exposed to AlCl3 (0, 64.18, 128.36 and 256.72 mg/kg BW) through drinking water for 120 days. The CD3(+), CD4(+), CD8(+) T lymphocytes, the T and B lymphocytes proliferation rates and serum NE concentration were examined. The correlation analysis between splenic immune function and NE were done. The results showed that the CD3(+), CD4(+), CD8(+) T lymphocytes and the T and B lymphocytes proliferation rates decreased and NE concentration increased in AlCl3-treated rats. NE was negatively correlated with proportions of CD3(+), CD4(+) T lymphocytes and T and B lymphocytes proliferation rates, but not correlated with CD8(+) T lymphocytes. The results suggest that AlCl3 suppresses the splenic immune function and NE plays important role in this process.

Effects of norepinephrine on immune functions of cultured splenic lymphocytes exposed to aluminum trichloride.

The aim of this study was to investigate the effect of norepinephrine (NE) on spleen lymphocytes exposed to aluminum trichloride (AlCl3). In this experiment, lymphocytes were isolated from spleens of healthy Wistar rats weighing about 130 g and cultured with RPMI-1640 medium containing the final concentration of 0.552 mmol/L AlCl3. NE was added to the cultured cells at the final concentrations of 0 (control group), 0.1 (low-dose group), 1 (mid-dose group), and 10 (high-dose group) nmol/L. No addition of both AlCl3 and NE serviced as blank (BG). The T lymphocyte proliferation; the contents of IL-2, TNF-α, and T lymphocyte subsets; immunoglobulin G (IgG) and intracellular cyclic adenosine monophosphate (cAMP) concentrations; and ß2-adrenergic receptor (ß2-AR) density were measured at the end of the culture. The result showed that NE decreased T lymphocyte proliferation and the contents of IL-2, TNF-α, and T lymphocyte subsets whereas increased the concentrations of IgG and intracellular cAMP and ß2-AR density of the lymphocyte exposed to AlCl3. AlCl3 exposure without adding NE showed the similar impacts on these measures compared with BG. The results suggested that NE aggravated AlCl3 immunotoxicity on the lymphocytes and disordered the immune functions of the lymphocyte through the ß2-AR-cAMP signal pathway.

Effects of aluminum on immune functions of cultured splenic T and B lymphocytes in rats.

The effects of Aluminum (Al) exposure on immune functions of cultured splenic T and B lymphocytes of rats were studied. The lymphocytes were isolated from spleen of healthy male Wistar rats weighing 110-120 g. The cultured cells in RPMI-1640 medium were exposed to 0 (control group), 0.035 (low-dose group), 0.07 (medial-dose group), and 0.14 (high-dose group) mg/mL Al(3+) as aluminum trichloride (AlCl(3)) in an incubator under 5% CO(2) at 37°C for 24 h. The T and B lymphocyte proliferation was measured with a tetrazolium dye colorimetric assay. The levels of interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α were determined by iodine [(125)I] IL-2, IL-6, and TNF-α radioimmunoassay kits, respectively. The proportions of CD3(+), CD4(+), and CD8(+) T lymphocytes were measured with a flow cytometer. The results showed that the T and B lymphocyte proliferation, the levels of IL-2, IL-6, TNF-α, the proportions of CD3(+) and CD4(+) T lymphocytes, and the ratio of CD4(+)/CD8(+) T lymphocytes were lowered by Al treatments, while the proportion of CD8(+) T lymphocytes was increased. These findings indicate that Al exposure can inhibit the immune functions of splenic T and B lymphocytes of rats in vitro.