Primary hepatic neuroendocrine neoplasms: imaging characteristics and misdiagnosis analysis.

Objective: To analyze the CT and MR features of Primary hepatic neuroendocrine neoplasms (PHNENs) in order to enhance the diagnostic accuracy of this disease. Methods: A retrospective analysis was conducted on patients diagnosed with hepatic neuroendocrine neoplasms, excluding other sites of origin through general examination and postoperative follow-up. The CT and MR signs were analyzed according to the 2018 version of Liver Imaging Reporting and Data System (LI-RADS), along with causes of misdiagnosis. Results: Twelve patients, including 6 males and 6 females, were enrolled in this study. There was no significant increase in liver tumor markers among all cases. Most masses were multiple (9/12), exhibiting low attenuation on pre-contrast CT scans, T1-hypointense signal, T2-hyperintense signal, and restricted diffusion. The majority of these masses (7/10) demonstrated similar rim arterial phase hyper-enhancement as well as peripheral "washout" during venous portal phase and delayed phase imaging. Three cases had incomplete capsules while one case had a complete capsule. Cyst/necrosis was observed in 7 out of all cases following administration of contrast agent, with 5 mainly distributed in the periphery. All masses lacked fat, calcification, vascular or bile duct tumor thrombus formation. Conclusion: The imaging findings associated with PHNENs possess certain specificity, often presenting as multiple masses within the liver accompanied by peripheral cyst/necrosis, similar rim arterial phase hyper-enhancement during venous portal phase and delayed phase imaging.

Renal Lesions with Low-level Enhancement on Contrast-enhanced CT Promotes Early Detection of Drug-induced Kidney Injury in Patients Administered Anticancer Drugs.

BACKGROUND: Some patients with cancer-administered anti-cancer drugs may develop renal lesions with low-level enhancement on follow-up abdominal computed tomography (CT). OBJECTIVE: To explore the clinical significance of renal lesions with low-level enhancement on CT after exposure to anti-cancer drugs. METHODS: Medical records of patients with cancer who developed renal lesions on CT after exposure to anti-cancer drugs were retrospectively reviewed. Renal lesions were scored according to the extent of involvement, CT attenuation values of lesions and normal parenchyma were measured on precontrast CT and three phases of contrast-enhanced CT, and changes in serum creatinine (SCr) from one week before exposure to drugs to one week before and after the appearance of renal lesions were recorded. RESULTS: This study included 54 patients (86 lesions). Lesions were slightly lower density on pre-contrast CT, and less enhancing than normal renal parenchyma, especially in the delayed phase. Lesions were wedge-shaped, and involved the renal pyramid and associated renal cortex, as well as, were single or multiple, and occurred in the unilateral or bilateral kidneys. There were patchy and cord-like shadows of increased density in adjacent perirenal adipose tissue. During follow-up, lesions disappeared in 15 patients and persisted in 39 patients without significant progression. There were significant differences in renal lesions and normal renal parenchyma CT attenuation values in each phase of contrast-enhanced CT. Change in SCr level was significantly positively correlated with lesion score. CONCLUSION: Renal lesions with low-level enhancement on CT suggest early drug-induced kidney injury. These findings will inform clinical decision-making.

Hydroxysafflor yellow A protects against colitis in mice by suppressing pyroptosis via inhibiting HK1/NLRP3/GSDMD and modulating gut microbiota.

Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5'-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1ß, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.

Cordycepin exhibits anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway.

Fatigue, a most commonly sub-health condition, may cause people more susceptible to many diseases. Cordycepin, a principal active ingredient from Cordyceps militaris, exerts various pharmacological activities including anti-diabetes, anti-inflammatory, immunomodulatory and antioxidant effects. However, the anti-fatigue effect of cordycepin and specific mechanism remained unclear. This study aimed to investigate the beneficial effect of cordycepin on physical fatigue and elucidate the potential mechanism. 20 mg/kg, 40 mg/kg of cordycepin and 500 mg/kg taurine were respectively treated to mice for 28 days before weight-loaded swimming test. The results revealed that cordycepin significantly prolonged the weight-loaded swimming time of mice. Meanwhile, cordycepin decreased the levels of lactic acid, blood uric nitrogen, and malondialdehyde, and increased the contents of superoxide dismutase, glutathione, nicotinamide adenine dinucleotide phosphate, hepatic glycogen, muscle glycogen and ATP. The metabolomic study by GC-MS showed that eight biomarkers were found in livers, including L-lactic acid, L-asparagine, 3-phosphoglyceric acid, inosine, D-galactose, L-tyrosine, glyceric acid and L-threonine. There were seven biomarkers in gastrocnemius, including D-ribose-5-phosphate, acetic acid, propionic acid, butyric acid, palmitic acid, oxaloacetic acid and citric acid. The results of metabolomics indicated that cordycepin might relieve fatigue by regulating energy metabolism and pentose phosphate pathway. Furthermore, we found cordycepin significantly enhanced the protein levels of TIGAR, SIRT1, PGC-1α, NRF1 and TFAM in gastrocnemius of weight-loaded swimming mice. Taken together, the present study demonstrated that cordycepin possessed an anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway. Our study indicated that cordycepin may be a potentially efficient candidate for fatigue.

Imaging Observation of Nano-Artificial Bone in the Repair of the Defect in Osteonecrosis of the Femoral Head.

To observe the effect of nano-artificial bone and bone marrow mesenchymal stem cells (BMSCs) in the treatment of femoral head osteonecrosis. The bilateral femoral head internal bone defect model was established and divided into three groups. Group A was used to make the defect without filling any material as the control, group B was only filled with nano-artificial bone, and group C was filled with composite materials of nano-artificial bone and bone marrow mesenchymal stem cells. The femoral head was examined using radiography and high-resolution focused 48-slice computed tomography (CT) at 12 weeks after implantation. A significant difference was found between groups B and C in the aspect of repairing the defect in osteogenesis of the femoral head as compared with the control group. Nano-collagen-based bone has strong osteogenic and osteogenic effects and is a good graft material for repairing bone defects of the femoral head. The use of bone marrow mesenchymal stem cells can promote the repair of bone defects, which is of great value in the treatment of osteonecrosis of the femoral head.

Exogenous NADPH ameliorates myocardial ischemia-reperfusion injury in rats through activating AMPK/mTOR pathway.

Our previous study shows that nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in protecting against cerebral ischemia injury. In this study we investigated whether NADPH exerted cardioprotection against myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion, NADPH (4, 8, 16 mg· kg-1· d-1, iv) was administered to the rats. We found that NADPH concentrations in plasma and heart were significantly increased at 4 h after intravenous administration. Exogenous NADPH (8-16 mg/kg) significantly decreased myocardial infarct size and reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I). Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to oxygen-glucose deprivation/restoration (OGD/R). Pretreatment with NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis. NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases.

miR-181b-5p suppresses starvation-induced cardiomyocyte autophagy by targeting Hspa5.

This study aimed to investigate the role of microRNA­181b­5p (miR­181b­5p) in starvation­induced cardiomyocyte autophagy by targeting heat shock protein family A member 5 (Hspa5). For this purpose, H9c2 cardiomyocytes and neonatal rat ventricular myocytes (NRVMs) were glucose­starved in Earle's Balanced Salt Solution (EBSS) for different periods of time (0, 2, 4, 6 and 8 h). RT­qPCR analysis was performed to examine the expression of miR­181b­5p in the different groups. Immunofluorescence was performed to detect the expression of LC3. In addition, the H9c2 cardiomyocytes and NRVMs were transfected with miR­181b­5p mimic, miR­181b­5p inhibitor, siHspa5 or their respective controls. An MTT assay was performed to measure cell proliferation in the different groups. Western blot analysis was performed to determine the expression of Beclin­1, Hspa5, phosphorylated phosphoinositide 3­kinase PI3K (p­PI3K), phosphorylated Akt (p­Akt), phosphorylated mammalian target of rapamycin (p­mTOR), Bcl­2, Bax and cleaved caspase­3. Flow cytometry was performed to assess cell apoptosis. A luciferase reporter assay was performed to determine whether Hspa5 is a direct target of miR­181b­5p. The results revealed that the downregulation of miR­181b­5p promoted cell autophagy in the cardiomyocytes. Moreover, miR­181b­5p negatively regulated Beclin­1 and Hspa5. Beclin­1 is a well­known autophagy­ and apoptosis­related protein. In addition, cell apoptosis was attenuated by the decreased expression of miR­181b­5p in the cardiomyocytes. Bcl­2 prevented apoptosis and autophagy by binding to Bax and Bcl­2, respectively. The upregulation of miR­181b­5p inhibited autophagy and promoted apoptosis via Hspa5. miR­181b­5p inhibition promoted p­mTOR, p­Akt and p­PI3K expression via Hspa5. The results of luciferase reporter assay also confirmed that Hspa5 is a direct target of miR­181b­5p. On the whole, the findings of this study suggest that miR­181b­5p contributes to starvation­induced autophagy and apoptosis in cardiomyocytes by directly targeting Hspa5 via the PI3K/Akt/mTOR signaling pathway.