Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway.

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.

Fucoxanthin Inhibits the Proliferation and Metastasis of Human Pharyngeal Squamous Cell Carcinoma by Regulating the PI3K/Akt/mTOR Signaling Pathway.

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

The priming effects of plant leachates on dissolved organic matter degradation in water depend on leachate type and water stability.

The modification of dissolved organic matter (DOM) degradation by plant carbon inputs represents a critical biogeochemical process that controls carbon dynamics. However, the priming effects (PEs) different plant tissues induce on the degradation of DOM pools with different stabilities remain unknown. In this study, PEs, induced by different tissue leachates of Phragmites australis, were evaluated via changes in DOM components and properties of both fresh and tidal water (with different stabilities). The results showed that DOM derived from different plant tissue leachates differed in composition and bioavailability. Inputs of tissue leachates induced PEs with different intensities and directions (negative or positive) on DOM degradation of fresh and tidal water. In fresh water, the PEs of leaf and root leachates were significantly higher than those of stem and rhizome leachates. The PE direction changed for DOM degradation between fresh and tidal water. The addition of leaf and root leachates tended to induce positive PEs on DOM degradation of fresh water, while resulting in negative PEs on DOM degradation of tidal water. Negative PEs for tidal water DOM may be due to preferential utilization of microbes, high salinity, and/or the promotion of exogenous DOM production from plant tissues. The results indicate that intensity and direction of PEs induced by plant leachates depend on both leachate type and water stability. The findings highlight the necessity to examine the nature of exogenous and native DOM when interpreting the interactive processes that regulate DOM degradation.

Differential diagnosis of coronavirus disease 2019 pneumonia or influenza A pneumonia by clinical characteristics and laboratory findings.

BACKGROUND: Pneumonia caused by the 2019 novel Coronavirus (COVID-2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify their clinical characteristics to help early diagnosis. METHODS: We retrospectively retrieved data for laboratory-confirmed patients admitted with COVID-19-induced or influenza A-induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients' epidemiological and clinical features, as well as radiologic and laboratory findings. RESULTS: The median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID-19 cohort exhibited higher proportions of fatigue, diarrhea and ground-glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red-cell count, hemoglobin and albumin and presented lower levels of monocytes, c-reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground-glass opacity, and higher level of albumin were independent risk factors for COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia. CONCLUSIONS: In terms of COVID-19 pneumonia and influenza A pneumonia, fatigue, ground-glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.

Growth inhibition and metabolomic analysis of Xanthomonas oryzae pv. oryzae treated with resveratrol.

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) can cause destructive bacterial blight in rice. As an antibacterial, resveratrol may inhibit Xoo growth. This study focused on the potential structural-activity relationship of resveratrol and its derivatives against Xoo growth, and 1H-NMR-based metabolomic analysis was applied to investigate the global metabolite changes in Xoo after resveratrol treatment. RESULTS: Resveratrol showed the strongest inhibitory effects on Xoo growth compared with its derivatives, which lacked double bonds (compounds 4-6) or hydroxyls were substituted with methoxyls (compounds 7-9). The IC50 of resveratrol against Xoo growth was 11.67 ± 0.58 µg/mL. Results indicated that the double bond of resveratrol contributed to its inhibitory effects on Xoo growth, and hydroxyls were vital for this inhibition. Interestingly, resveratrol also significantly inhibited Xoo flagellum growth. Based on 1H-NMR global metabolic analysis, a total of 30 Xoo metabolites were identified, the changes in the metabolic profile indicated that resveratrol could cause oxidative stress as well as disturb energy, purine, amino acid, and NAD+ metabolism in Xoo, resulting in the observed inhibitory effects on growth. CONCLUSIONS: This study showed that the double bond of resveratrol contributed to its inhibitory effects on Xoo growth, and hydroxyls were also the important active groups. Resveratrol could cause oxidative stress of Xoo cells, and disturb the metabolism of energy, purine, amino acid and NAD +, thus inhibit Xoo growth.

Enhanced stability of a rumen-derived xylanase using SpyTag/SpyCatcher cyclization.

Microbiota from herbivore rumen is of great interest for mining glycoside hydrolases for lignocellulosic biomass biorefinement. We previously isolated a highly active but poorly thermostable xylanase (LXY) from a rumen fluid fosmid library of Hu sheep, a local high-reproductive species in China. In this study, we used a universal enzyme-engineering strategy called SpyTag/SpyCatcher molecular cyclization to improve LXY stability via isopeptide-bond-mediated ligation. Both linear and cyclized LXY (L- and C-LXY, respectively) shared similar patterns of optimal pH and temperature, pH stability, and kinetic constants (km and Vmax). However, the C-LXY showed enhanced thermostability, ion stability, and resilience to aggregation and freeze-thaw treatment than L-LXY, without compromise of its catalytic efficiency. Circular dichroism and intrinsic and 8-anilino-1-naphthalenesulfonic acid-binding fluorescence analysis indicated that the cyclized enzyme was more capable of maintaining its secondary and tertiary structures than the linear enzyme. Taken together, these results promote the cyclized enzyme for potential applications in the feed, food, paper pulp, and bioenergy industries.

Advances in genome-wide association study of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and chronic airway inflammation, caused by a combination of environmental and genetic factors. It is the third leading cause of death worldwide. In recent years, researchers have applied the genome-wide association study (GWAS) and identified a large number of genetic variants associated with lung functions and potential drug targets for treating COPD. In this review, we summarize the results of GWAS studies and perform a review of the literature since 2007 to highlight the progress of GWAS on COPD. We discuss the challenges, the underlying mechanisms, and the possible drug targets, thereby providing insights on the pathogenesis and potential treatment strategies for COPD.

[Recent advances in nephronectin].

Nephronectin (NPNT) is a novel extracellular matrix protein and a new ligand of integrin α8ß1. Recent studies showed that NPNT is highly expressed in kidney, lung, thyroid, etc, and it may play an important role in many pathological conditions. NPNT is involved in the process of kidney development and acute kidney injury, regulates proliferation and differentiation of osteoblast, and induces the vasculogenesis in vitro. NPNT may play a key role in pathological osteoporosis and therefore be a new therapeutic target of bone diseases. NPNT gene variants are not only associated with lung function, but also potentially implicated in chronic airway diseases development. Moreover, NPNT is also an important factor that mediates pathology of cardiac, epidermis, breast, liver and teeth diseases. In this paper, we reviewed some research progresses on the structure, distribution, physiological and pathophysiological functions of NPNT.

Identification of non-canonical antagonistic bacteria via interspecies contact-dependent killing.

BACKGROUND: Canonical biocontrol bacteria were considered to inhibit pathogenic bacteria mainly by secreting antibiotic metabolites or enzymes. Recent studies revealed that some biocontrol bacteria can inhibit pathogenic bacteria through contact-dependent killing (CDK) mediated by contact-dependent secretion systems. The CDK was independent of antibiotic metabolites and often ignored in normal biocontrol activity assay. RESULTS: In this study, we aimed to use a pathogen enrichment strategy to isolate non-canonical bacteria with CDK ability. Rhizosphere soil samples from Chinese cabbage showing soft rot symptom were collected and Pectobacterium carotovorum subsp. carotovorum (Pcc), the pathogen of cabbage soft rot, were added into these samples to enrich bacteria which attached on Pcc cells. By co-culture with Pcc, four bacteria strains (named as PcE1, PcE8, PcE12 and PcE13) showing antibacterial activity were isolated from Chinese cabbage rhizosphere. These four bacteria strains showed CDK abilities to different pathogenic bacteria of horticultural plants. Among them, PcE1 was identified as Chryseobacterium cucumeris. Genome sequencing showed that PcE1 genome encoded a type VI secretion system (T6SS) gene cluster. By heterologous expression, four predicted T6SS effectors of PcE1 showed antibacterial activity to Escherichia coli. CONCLUSION: Overall, this study isolated four bacteria strains with CDK activity to various horticultural plant pathogens, and revealed possible involvement of T6SS of Chryseobacterium cucumeris in antibacterial activity. These results provide valuable insight for potential application of CDK activity in biocontrol bacteria. © 2024 Society of Chemical Industry.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint: A Retrospective Analysis.

OBJECTIVE: To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy. METHODS: After retrospectively screening the data of 742 patients between January 2007 and July 2020, 50 patients aged 13 to 39 years with Enneking stage II disease were included in the study. Serum lipid levels, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-α [Lp(a)], and apolipoprotein A1, B, and E (ApoA1, ApoB, and ApoE), and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy. RESULTS: The mean levels of TC, TG, and ApoB were significantly increased following neoadjuvant chemotherapy (16%, 38%, and 20%, respectively, vs. pretreatment values; P<0.01). The mean levels of LDL-C and ApoE were also 19% and 16% higher, respectively (P<0.05). No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy. An increase in Lp(a) was strongly correlated with the Ki-67 index (R=0.31, P=0.023). Moreover, a trend toward longer disease-free survival (DFS) was observed in patients with decreased TG and increased LDL-C following chemotherapy, although this difference was not statistically significant (P=0.23 and P=0.24, respectively). CONCLUSION: Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma. There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy. The scale of increase in serum Lp(a) might have a potential prognostic role in osteosarcoma. Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

Thermal ablation versus repeated hepatic resection for recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Repeated hepatic resection (HR) and thermal ablation therapy (TAT) are increasingly being used to treat recurrent intrahepatic cholangiocarcinoma (RICC). This study compared the efficacy and safety of these procedures for RICC treatment. METHODS: Patients were studied retrospectively after curative resection of RICCs by repeated HR (n = 32) or TAT (n = 77). Treatment effectiveness and prognosis were compared between the two treatment groups. RESULTS: The repeated HR and TAT groups did not differ in their overall survival (OS; p = 0.996) or disease-free survival (DFS; p = 0.692) rates. However, among patients with recurrent tumors >3 cm in diameter, patients in the repeated HR group had a higher OS rate than patients in the TAT group (p = 0.037). The number of recurrent tumors and the recurrence interval were significant prognostic factors for OS. The major complications incidence rate was greater in the repeated HR group than in the TAT group (p < 0.001). CONCLUSIONS: Repeated HR and TAT are both effective treatments for RICC with similar overall efficacies. TAT should be preferred in any cases when the RICC is ≤3 cm in diameter and technically feasible. However, for large tumors (>3 cm), repeated HR may be a better choice.

[Using in-situ reflectance to monitor the chlorophyll concentration in the surface layer of tidal flat].

An optical monitoring method is proposed for the rapid, non destructive measurements of chlorophyll concentration (Chl-a) in the surface sediments of emerged tidal flat, and it can be further applied in remote sensing work. Hyperspectral reflectance of intertidal sediments were measured in day time at the tidal flats of the Sishili Bay, the Northern Yellow Sea, and surface sediments (3 mm) were sampled for the in-door measurements of Chl-a. On the basis of the reflectance at 650, 675 and 700 nm, the indices of normalized difference index of microbenthos (NDI-MPB) and trough depth (T-depth) were proposed for the measurements of microphytobenthos biomass. T-depth can be used to remove the linear background spectral noises and indicate the existence of microphytobenthos; Good linear relationship was observed between NDI-MPB and Chl-a content in sediments (2.22-49.36 mg x m(-2), r > 0.99), which may be used to monitor the biomass of microphy to benthos.

Association between sedentary behavior and risk of cognitive decline or mild cognitive impairment among the elderly: a systematic review and meta-analysis.

Background: Existing evidence on the association between sedentary behavior (SB) and cognitive function remains inconclusive. Therefore, this study investigated the association between SB and the risk of cognitive decline (CD) or mild cognitive impairment (MCI) in the elderly. Methods: A comprehensive search was independently conducted by two researchers (XC and GQ) in seven electronic databases, including Medline (via PubMed), China Biology Medicine, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang database, and VIP database for Chinese technical periodicals, covering studies published from the inception of database to June 2023. Studies that investigated the relationship between SB and the risk of CD or MCI in the elderly were included. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) assessment tools. The combined effect size analysis, subgroup analysis, and publication bias assessment were performed using STATA 14.0. Results: A total of 13 cross-sectional and 6 cohort studies involving 81,791 individuals were included, comprising 17 high-quality studies and 2 medium-quality studies. We found that SB was significantly associated with an increased risk of CD [odds ratio (OR) = 1.69, 95% confidence intervals (CI): 1.47-1.94] or MCI (OR = 1.34, 95% CI: 1.14-1.56) among the elderly. Subgroup analysis stratified according to comorbidity, lifestyle, family structure, publication year, and region showed statistical differences between groups, and the consistency of the results revealed the sources of the heterogeneity. Conclusion: This meta-analysis showed that SB is positively associated with the risk of CD or MCI in the elderly, providing a higher level of evidence for the promotion of healthy behaviors by clinicians and health policymakers. Due to the number and quality of the included articles, more high-quality longitudinal studies are needed to further confirm our findings.

Seasonal spermatogenesis, epididymal storage, and creatine kinase expression in Pelodiscus sinensis.

The soft-shelled turtle, Pelodiscus sinensis, is an important economic aquaculture species. Its reproduction exhibits seasonality; however, there is a lack of systematic studies focused on sperm maturation and epididymal storage. The testes and epididymides of P. sinensis were sampled from March to December. The seasonal reproduction and maturation of the spermatozoa were examined by anatomy, hematoxylin and eosin staining, AB-PAS staining, and immunohistochemistry. Spermatogenesis exhibited obvious seasonality in P. sinensis. It was found that the spermatogenic epithelium was most active during June to September, whereas the diameter of the epididymal tubules was smallest during June to October. As key enzymes of ATP metabolism, creatine kinases were highly expressed in the epididymal tubule epithelium during the breeding season, which may be important for the regulation of sperm maturation. In addition, the epididymal tubule epithelium changed with the season in June to September, the epididymal tubule epithelium proliferated to form villous structures, and secreted a large number of glycoproteins, which may be related to the rapid maturation of sperm during the breeding season. In conclusion, this study provided insights into the spermatogenesis of P. sinensis through histological analysis and enriched our understanding of reproduction in reptiles.

Role of the extracellular matrix in COVID-19.

An outbreak of coronavirus disease 2019 (COVID-19) has spread globally, with over 500 million cases and 6 million deaths to date. COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix (ECM), which is also involved in inflammatory storms. Upon viral infection, ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism, including in the lungs. Additionally, serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets. Consequently, understanding the expression and function of ECM, particularly of the lung, during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression. In this review, we summarize the current findings on ECM, such as hyaluronic acid, matrix metalloproteinases, and collagen, which are linked to the severity and inflammation of COVID-19. Some drugs targeting the extracellular surface have been effective. In the future, these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.

Analysis of human Ki-67 gene promoter and identification of the Sp1 binding sites for Ki-67 transcription.

Ki-67 as a cell proliferation marker is tightly associated with maintenance and regulation of the cell division. To understand the mechanism of Ki-67 gene expression and regulation, we first cloned 5'-flanking region and identified the Ki-67 core promoter. The deletion analysis and the dual luciferase reporter assay were used to locate the Ki-67 core promoter from -223 to +12 nt relative to the transcriptional initiation site, which is the TATA less, GC rich region comprised of several putative Sp1 binding sites. Compared with the hTERT promoter and Survivin promoter, the Ki-67 core promoter possessed higher transcription activity and more desirable tumor selectivity. In order to further demonstrate the contribution of transcription factor Sp1 on regulating the Ki-67 gene transcription, we confirmed three Sp1 binding sites from -170 to -145 nt, from -63 to -38 nt, and from -14 to +12 nt existed in the Ki-67 core promoter by the supershift assay. The deletion mutagenesis, together with the dual luciferase reporter assay, indicated that these Sp1 binding sites, particularly the region from -170 to -145 nt, were involved in positive regulation of the Ki-67 gene expression. Collectively, it was demonstrated that the region from -223 to +12 nt could drive the transcription of the Ki-67 gene, and the Sp1 binding site is essential to transcriptional regulation of the Ki-67 gene.

Efficacy of microwave versus radiofrequency ablation for treatment of small hepatocellular carcinoma: experimental and clinical studies.

OBJECTIVE: To prospectively compare microwave (MW) ablation using a modified internal cooled-shaft antenna with radiofrequency (RF) ablation in in vivo porcine liver and in patients with small hepatocellular carcinoma (sHCC). METHODS: In an animal study, MW and RF ablations using a cooled-shaft antenna or internally cooled electrode were performed in in vivo porcine liver. Coagulation diameters of both ablations were compared. For clinical study, 42 patients with sHCC were treated with MW or RF ablation. Complete ablation (CA) and local tumour progression (LTP) were compared. RESULTS: MW ablation produced significantly larger ablation zones than RF ablation in both porcine liver and sHCC with an ablated volume of 33.3 ± 15.6 cm(3) vs. 18.9 ± 9.1 cm(3) and 109.3 ± 58.3 cm(3) vs. 48.7 ± 30.5 cm(3), respectively. The CA rate was 95.5 % (21/22) for MW ablation and 95.0 % (19/20) for RF ablation. In a 5.1-month follow-up, the LTP rate was 18.2 % (4/22) in the MW ablation group and 15.0 % (3/20) in the RF ablation group. CONCLUSION: MW ablation using a modified cooled-shaft antenna produces a larger ablation zone than RF ablation, with an efficacy similar to RF ablation in local tumour control. MW ablation is a safe and promising treatment of sHCC.

Effects of isorhamnetin on tyrosinase: inhibition kinetics and computational simulation.

We studied the inhibitory effects of isorhamnetin on mushroom tyrosinase by inhibition kinetics and computational simulation. Isorhamnetin reversibly inhibited tyrosinase in a mixed-type manner at Ki=0.235±0.013 mM. Measurements of intrinsic and 1-anilinonaphthalene-8-sulfonate(ANS)-binding fluorescence showed that isorhamnetin did not induce significant changes in the tertiary structure of tyrosinase. To gain insight into the inactivation process, the kinetics were computed via time-interval measurements and continuous substrate reactions. The results indicated that inactivation induced by isorhamnetin was a first-order reaction with biphasic processes. To gain further insight, we simulated docking between tyrosinase and isorhamnetin. Simulation was successful (binding energies for Dock6.3: -32.58 kcal/mol, for AutoDock4.2: -5.66 kcal/mol, and for Fred2.2: -48.86 kcal/mol), suggesting that isorhamnetin interacts with several residues, such as HIS244 and MET280. This strategy of predicting tyrosinase interaction in combination with kinetics based on a flavanone compound might prove useful in screening for potential natural tyrosinase inhibitors.

Pathologic features and clinical outcome of central neurocytoma: analysis of 15 cases.

OBJECTIVE: To get better recognition of central neurocytoma and diminish misdiagnosis. METHODS: A retrospective review identified 15 cases of central neurocytoma. All cases of central neurocytoma were analyzed for their clinical symptoms, pathologic changes, immunohistochemical staining, prognosis and differential diagnosis. Clinical follow up was performed. RESULTS: There were 8 males and 7 females aged 10-64 years (median 32.93 years). The most common presenting symptoms were those related to increased intracranial pressure (ICP), including headache (100%), papilledema (93%) and vomiting (80%). All tumors were located in the ventricular system. The tumors were composed of uniform cells with round nuclei and a fine chromatin pattern, and in some areas, small cells with perinuclear halo could be seen. In particular, the anuclear areas may have a fine fibrillary matrix (neuropil). Nuclear atypia and vascular proliferation appeared in two cases, respectively. Focal necrosis could be seen in one case. Immunohistochemical findings included expression of synaptophysin (15/15), neuron specific enolase (12/15) and glial fibrillary acidic protein (GFAP) (3/15). MIB-1 proliferation index ranged from 0.8-12.5%, and was more than 2% in 3 of 15 cases assessed. Follow-up information of 11 patients was available. CONCLUSIONS: Central neurocytoma has a favorable prognosis in general, but in some cases, the clinical course could be aggressive. Increase of GFAP positivity, proliferation index and vascular proliferation might suggest a more malignant process.

Body mass index and outcomes of patients with cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: Cardiogenic shock continues to be a highly morbid complication that affects around 7%-10% of patients with acute myocardial infarction or heart failure. Similarly, obesity has become a worldwide epidemic. AIM: To analyze the impact of higher body mass index (BMI) on outcomes of patients with cardiogenic shock. METHODS: A systematic and comprehensive search was undertaken on the electronic databases of PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar for all types of studies comparing mortality outcomes of patients with cardiogenic shock based on BMI. All studies defined overweight or obese patients based on the World Health Organization BMI criteria. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS: Five studies were included. On pooled analysis of multivariable-adjusted ratios, we noted a statistically significantly reduced risk of mortality in overweight/obese vs normal patients (three studies; odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.85-0.98, I 2 = 85%). On meta-analysis, we noted that crude mortality rates did not significantly differ between overweight/obese and normal patients after cardiogenic shock (OR = 0.95, 95%CI: 0.79-1.15, I 2 = 99%). The results were not stable on sensitivity analysis and were associated with substantial heterogeneity. CONCLUSION: Current evidence on the association between overweight/obesity and mortality after cardiogenic shock is scarce and conflicting. The obesity paradox might exist in patients with cardiogenic shock but could be confounded by the use of mechanical circulatory support. There is a need for further studies to clarify this relationship.