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Open Access
April 1, 2023
Abstract
Background The prospective relationship between plasma vitamin E levels and proteinuria remains uncertain. We aimed to evaluate the association between baseline plasma vitamin E levels and the development of proteinuria and examine any possible effect modifiers in patients with hypertension. Methods This was a post hoc analysis of the renal sub-study of the China Stroke Primary Prevention Trial (CSPPT). In total, 780 participants with vitamin E measurements and without proteinuria at baseline were included in the current study. The study outcome was the development of proteinuria, defined as a urine dipstick reading of a trace or ≥ 1+ at the exit visit. Results During a median follow-up duration of 4.4 years, the development of proteinuria occurred in 93 (11.9%) participants. Overall, there was an inverse relationship between plasma vitamin E and the development of proteinuria (per standard deviation [SD] increment; odds ratio [OR]: 0.73, 95% confidence interval [CI]: 0.55–0.96). Consistently, when plasma vitamin E was assessed as quartiles, lower risk of proteinuria development was found in participants in quartiles 2–4 (≥ 7.3 μg/mL; OR: 0.57, 95% CI: 0.34–0.96) compared to those in quartile 1. None of the variables, including sex, age, and body mass index, significantly modified the association between vitamin E and proteinuria development. Conclusion There was a significant inverse association between plasma vitamin E levels and the development of proteinuria in patients with hypertension. The results were consistent among participants with different baseline characteristics.
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Open Access
March 19, 2023
Abstract
Background Morphologic changes in the gallbladder and gallstones are common in cirrhotic patients, but their associations with outcomes of cirrhotic patients are unclear. Methods We retrospectively enrolled 206 cirrhotic patients and measured their gallbladder length and width, gallbladder wall thickness, presence of gallstones, and gallstones’ length and width in axial contrast-enhanced computed tomography (CT) images. X-tile software was utilized to calculate the optimal cutoff values of these parameters for evaluating survival and hepatic decompensation events in the cirrhosis group. Their associations with survival were explored by Cox regression analyses and Kaplan–Meier curve analyses. Their associations with hepatic decompensation events were evaluated by competing risk analyses and Nelson-Aalen cumulative risk curve analyses where death was a competing event. Results Cirrhotic patients with gallbladder length < 72 mm had a significantly higher cumulative survival rate than those with a length of ≥ 72 mm ( P = 0.049 by log-rank test), but gallbladder width, gallbladder wall thickness, presence of gallstones, and gallstones’ length and width were not significantly associated with survival ( P = 0.10, P = 0.14, P = 0.97, P = 0.73, and P = 0.73 by log-rank tests, respectively). Cirrhotic patients with gallbladder wall thickness < 3.4 mm had a significantly lower cumulative rate of hepatic decompensation events than those with a wall thickness of ≥ 3.4 mm ( P = 0.02 by Gray’s test), but gallbladder length and width, presence of gallstones, and gallstones’ length and width were not significantly associated with hepatic decompensation events ( P = 0.15, P = 0.15, P = 0.54, P = 0.76, and P = 0.54 by Gray’s tests, respectively). Conclusion Changes in gallbladder length and gallbladder wall thickness, rather than gallstone parameters, may be in parallel with the long-term outcomes of cirrhotic patients.
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Open Access
March 19, 2023
Abstract
Gouty arthritis, often referred to simply as gout, is a disorder of purine metabolism characterized by the deposition of monosodium urate monohydrate (MSU) crystals in multiple systems and organs, especially in joints and their surrounding soft tissue. Gout is a treatable chronic disease, and the main strategy for effective management is to reverse the deposition of MSU crystals by uric acid reduction, and to prevent gout attacks, tophi deposition and complications, and thereby improve the quality of life. However, the frequent association of gout with other conditions such as hypertension, obesity, cardiovascular disease, diabetes, dyslipidemia, chronic kidney disease (CKD) and kidney stones can complicate the treatment of gout and lead to premature death. Here, we review the use of medical imaging techniques for studying gouty arthritis with special interest in the potential role of single photon emission computed tomography (SPECT)/computed tomography (CT) in the clinical management of gout and complications ( e.g. , chronic kidney disease and cardiovascular disease).
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Open Access
March 19, 2023
Abstract
Background and Objectives Local hyperthermia at 44℃ can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia eficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44℃ and 37℃ water baths for 30 min). Methods The succinylome analysis was conducted on HaCaT subjected to 44℃ and 37℃ water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein–protein interaction (PPI) was performed. Results A total of 119 proteins with 197 succinylated sites were upregulated in 44℃-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2. Conclusions Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts.
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Open Access
March 19, 2023
Abstract
Background and Objective Chronic thromboembolic pulmonary hypertension (CTEPH) is a lethal complication of pulmonary embolism involving pulmonary artery occlusion and microvascular disease. The glucose metabolism and reactive oxygen species (ROS) production may be perturbed in CTEPH, but the precise mechanisms are unclear. This study investigated glucose metabolism in CTEPH employing pulmonary endarterectomy (PEA)-derived pulmonary artery smooth muscle cells (PASMCs) and characterized the roles of pyruvate kinase M2 (PKM2) and its regulation by heterogeneous nuclear ribonucleoproteins A1 (hnRNPA1) and ROS in CTEPH. Methods PEA tissues and blood samples of CTEPH patients were collected to study the levels of PKM2. Primary PASMCs were isolated from PEA tissues. We used small interfering RNAs to knock down PKM2 and hnRNPA1 , and applied antioxidant N-acetylcysteine (NAC) and mito-TEMPO to reduce ROS production. The expression of glucometabolic genes, ROS production, glycolysis rate and proliferative and migratory activities were analyzed in PEA-derived PASMCs. Results PKM2 levels in serum and PEA tissues of CTEPH patients were higher than that of the healthy controls. Compared to the control PASMCs, PEA-derived PASMCs showed increased PKM2 expression and ROS production. The rates of glycolysis, proliferation and migration were increased in PEA-PASMCs and could be mitigated by PKM2 downregulation through hnRNPA1 or ROS inhibition. Conclusions Increased glycolysis and PKM2 expression were found in PEA-PASMCs. Inhibition of hnRNPA1 or ROS corrected the aberrant glycolysis, cell proliferation and migration by downregulating PKM2. Regulation of the hnRNPA1/PKM2 axis represents a potential therapeutic target for the treatment of CTEPH.
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Open Access
November 15, 2022
Abstract
Background and Objectives Haemodilution leads to complications in clinical practice. It is exactly unknown whether this damage is caused by the fluid or by the stretching of the vascular bed. We aimed to compare two different haemodilution techniques at the same anaemic level. Methods Normovolemic or hypervolemic haemodilution was performed on twelve adult male Wistar rats. In the normovolemic procedure, blood was withdrawn and instantaneously administered with similar amounts of 6% hydroxyethyl starch (HES 130/0.4). Fluid was administered without withdrawing blood in the hypervolemic procedure. In both models, a 25% haematocrit level was targeted and kept at this level for 90 min to deepen the anaemia effect. Besides haemodynamics measurement, renal function (creatinine, blood urea nitrogen) and injury (tissue norepinephrine, malondialdehyde) were evaluated. Also, systemic hypoxia (lactate), oxidative stress (malondialdehyde, ischaemia-modified albumin), inflammation (tumour necrosis factor-alpha [TNF-α]), osmotic stress, adrenal stress (norepinephrine, epinephrine), and vascular stretching (atrial natriuretic peptide [ANP]) were assessed. Results Arterial pressure in the normovolemic group was lower than in the hypervolemic group. Serum creatinine, blood urea nitrogen, and lactate levels were higher in the normovolemic group. Tissue norepinephrine and malondialdehyde levels were higher in the normovolemic group. Serum ANP, malondialdehyde, ischaemia-modified albumin, free haemoglobin, syndecan-1, and TNF-α were higher in both groups compared to respective baseline. Conclusions Normovolemic haemodilution may lead to hypoxic kidney injury. The hypervolemic state may be advantageous if fluid is to be administered. Thus, the effect of the fluid itself can be relatively masked.
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Open Access
November 15, 2022
Abstract
Background and Objectives The Alberta Stroke Program CT Score (ASPECTS) is a widely used rating system for assessing infarct extent and location. We aimed to investigate the prognostic value of ASPECTS subregions’ involvement in the long-term functional outcomes of acute ischemic stroke (AIS). Materials and Methods Consecutive patients with AIS and anterior circulation large-vessel stenosis and occlusion between January 2019 and December 2020 were included. The ASPECTS score and subregion involvement for each patient was assessed using posttreatment magnetic resonance diffusion-weighted imaging. Univariate and multivariable regression analyses were conducted to identify subregions related to 3-month poor functional outcome (modified Rankin Scale scores, 3–6) in the reperfusion and medical therapy cohorts, respectively. In addition, prognostic eficiency between the region-based ASPECTS and ASPECTS score methods were compared using receiver operating characteristic curves and DeLong’s test. Results A total of 365 patients (median age, 64 years; 70% men) were included, of whom 169 had poor outcomes. In the reperfusion therapy cohort, multivariable regression analyses revealed that the involvement of the left M4 cortical region in left-hemisphere stroke (adjusted odds ratio [aOR] 5.39, 95% confidence interval [CI] 1.53–19.02) and the involvement of the right M3 cortical region in right-hemisphere stroke (aOR 4.21, 95% CI 1.05–16.78) were independently associated with poor functional outcomes. In the medical therapy cohort, left-hemisphere stroke with left M5 cortical region (aOR 2.87, 95% CI 1.08–7.59) and caudate nucleus (aOR 3.14, 95% CI 1.00–9.85) involved and right-hemisphere stroke with right M3 cortical region (aOR 4.15, 95% CI 1.29–8.18) and internal capsule (aOR 3.94, 95% CI 1.22–12.78) affected were related to the increased risks of poststroke disability. In addition, region-based ASPECTS significantly improved the prognostic efficiency compared with the conventional ASPECTS score method. Conclusion The involvement of specific ASPECTS subregions depending on the affected hemisphere was associated with worse functional outcomes 3 months after stroke, and the critical subregion distribution varied by clinical management. Therefore, region-based ASPECTS could provide additional value in guiding individual decision making and neurological recovery in patients with AIS.
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Open Access
November 15, 2022
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an extremely high lethality rate. Oncogenic KRAS activation has been proven to be a key driver of PDAC initiation and progression. There is increasing evidence that PDAC cells undergo extensive metabolic reprogramming to adapt to their extreme energy and biomass demands. Cell-intrinsic factors, such as KRAS mutations, are able to trigger metabolic rewriting. Here, we update recent advances in KRAS-driven metabolic reprogramming and the associated metabolic therapeutic potential in PDAC.
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Abstract
Background and Objectives Non-hepatic hyperammonemia can damage the central nervous system (CNS), and possible prognostic factors are lacking. This study aimed to investigate the prognostic and risk factors for patients admitted to the intensive care unit (ICU). Materials and Methods This prospective, observational, multicenter study was conducted between November and December 2019 at 11 ICUs in the Chinese Heilongjiang province. Changes in blood ammonia level during and after ICU admission were continuously monitored and expressed as the high level (H-), mean level (M-), and initial level (I-) of ammonia. The risk factors of poor prognosis were investigated by conducting univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive ability of Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE-II) score, lactic acid, total bilirubin (TBil), and M-ammonia. Results A total of 1060 patients were included in this study, of which 707 (67%) had a favorable prognosis and 353 (33%) had a poor prognosis. As shown by univariate models, a poor prognosis was associated with elevated serum levels of lactic acid, TBil, and ammonia ( P < 0.05) and pathologic scores from three assessments: APACHE-II, Glasgow Coma Scale (GCS), and Sequential Organ Failure Assessment (SOFA). Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.07–2.80, P = 0.02). However, the APACHE-II score (area under the curve [AUC]: 0.714, sensitivity: 0.86, specificity: 0.68, P < 0.001) remained the most predictive factor for patient prognosis by ROC analysis. Conclusion Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.
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Open Access
June 10, 2022
Abstract
Chronic obstructive pulmonary disease (COPD) is a common inflammatory airway disease characterized by enhanced inflammation. Recent studies suggest that mitochondrial damage-associated molecular patterns (DAMPs) may play an important role in the regulation of inflammation and are involved in a serial of inflammatory diseases, and they may also be involved in COPD. This review highlights the potential role of mitochondrial DAMPs during COPD pathogenesis and discusses the therapeutic potential of targeting mitochondrial DAMPs and their related signaling pathways and receptors for COPD. Research progress on mitochondrial DAMPs may enhance our understanding of COPD inflammation and provide novel therapeutic targets.
