Facial Merkel cell carcinoma in a patient with diabetes and hepatitis B: A case report.

BACKGROUND: Patients with chronic inflammatory disorders are at a higher risk of developing aggressive Merkel cell carcinoma (MCC). Diabetes is a common chronic inflammatory disease that is possibly associated with MCC; however, there are still no reports on the association between hepatitis B virus (HBV) infection and MCC. Whether there is an association between these three diseases and the specific mechanisms behind their effects is worth further research in the future. CASE SUMMARY: We herein report a rare case of MCC with extracutaneous and nodal invasion in an Asian individual with type 2 diabetes mellitus and chronic HBV infection, but no immunosuppression or other malignancies. Such cases are uncommon and have rarely been reported in the literature. A 56-year-old Asian male presented with a significant mass on his right cheek and underwent extensive resection combined with parotidectomy, neck lymphadenectomy, and split-thickness skin grafting. Based on the histopathological findings, a diagnosis of MCC involving the adipose tissue, muscle, nerve, and parotid gland with lymphovascular invasion was made. Subsequently, he received radiotherapy with no adverse reactions. CONCLUSION: MCC is a rare, aggressive skin cancer with frequent local recurrence, nodal invasion, and metastasis, which usually arises in older people of the white race. Patients with chronic inflammatory disorders are at a higher risk of developing aggressive MCC. The diagnosis can be confirmed with histology and immunohistochemistry. For localized MCC, surgery is the preferred treatment option. However, for advanced MCC, radiotherapy and chemotherapy have proven to be effective. In cases where chemotherapy is not effective or in the advanced stages of MCC, immune therapy plays an important role in treatment. As with any rare disease, the management of MCC remains an enormous challenge for clinicians; thus, follow-up should be individualized and future progress needs multidisciplinary collaborative efforts. Furthermore, physicians should include MCC in their list of possible diagnoses when they come across painless, rapidly growing lesions, particularly in patients with chronic HBV infection or diabetes, as these patients are more susceptible to the development of this condition and it tends to be more aggressive in them.

Effects of social support, anxiety, and hope levels on cognitive bias in patients with nasogastric/nasoenteric tubes.

BACKGROUND: Unplanned extubation is a common adverse event and an important indicator of quality and safety of care. It is well recognized that the incidence of unplanned extubation of nasogastric/nasoenteric tubes is higher than that of other devices. Theory and previous research have suggested that cognitive bias in conscious patients with nasogastric/nasoenteric tubes may lead to unplanned extubation, and that social support, anxiety, and hope are influencing factors of cognitive bias. Therefore, the objective of this study was to investigate the effects of social support, anxiety, and hope levels on cognitive bias in patients with nasogastric/nasoenteric tubes. METHODS: In this cross-sectional study, 438 patients with nasogastric/nasoenteric tubes were selected from 16 hospitals in Suzhou from December 2019 to March 2022 by convenience sampling method. The participants were assessed using the General Information Questionnaire, Perceived Social Support Scale, Generalized Anxiety Disorder-7, Herth Hope Index, and Cognitive Bias Questionnaire for patients with nasogastric/nasoenteric tubes. The structural equation model was established with AMOS 22.0 software. RESULTS: The cognitive bias score of patients with nasogastric/nasoenteric tubes was 2.82±0.61. Patients' perceived levels of social support and hope were negatively correlated with their cognitive bias (r=-0.395 and -0.427, respectively, P<0.05), and anxiety was positively correlated with cognitive bias (r=0.446, P<0.05). Structural equation model analysis showed that anxiety had a direct positive effect on cognitive bias, with an effect value of 0.35 (P<0.001), and hope level had a direct negative effect on cognitive bias with an effect value of -0.33 (P<0.001). Social support had a direct negative effect on cognitive bias and was also shown to indirectly affect cognitive bias through anxiety and hope levels. The effect values were -0.22, -0.12, and -0.19 (P<0.001), for social support, anxiety, and hope, respectively. Social support, anxiety, and hope explained 46.2% of the total variation in cognitive bias. CONCLUSIONS: Moderate cognitive bias is noted in patients with nasogastric/nasoenteric tubes, and social support significantly affects cognitive bias. Anxiety and hope level play a mediating role in social support and cognitive bias. Positive psychological intervention and the obtention of positive support could improve the cognitive bias of patients with nasogastric/nasoenteric tubes.

TiO2-Coated Silicon Nanoparticle Core-Shell Structure for High-Capacity Lithium-Ion Battery Anode Materials.

Silicon-based anode materials are considered one of the highly promising anode materials due to their high theoretical energy density; however, problems such as volume effects and solid electrolyte interface film (SEI) instability limit the practical applications. Herein, silicon nanoparticles (SiNPs) are used as the nucleus and anatase titanium dioxide (TiO2) is used as the buffer layer to form a core-shell structure to adapt to the volume change of the silicon-based material and improve the overall interfacial stability of the electrode. In addition, silver nanowires (AgNWs) doping makes it possible to form a conductive network structure to improve the conductivity of the material. We used the core-shell structure SiNPs@TiO2/AgNWs composite as an anode material for high-efficiency Li-ion batteries. Compared with the pure SiNPs electrode, the SiNPs@TiO2/AgNWs electrode exhibits excellent electrochemical performance with a first discharge specific capacity of 3524.2 mAh·g-1 at a current density of 400 mA·g-1, which provides a new idea for the preparation of silicon-based anode materials for high-performance lithium-ion batteries.

Dual periodic event-triggered control for multi-agent systems with input saturation.

This paper is concerned with the periodic event-triggered consensus of multi-agent systems subject to input saturation. Due to the nonlinearity caused by the input saturation constraint, the accuracy of the event-triggered mechanism to screen data will be reduced. To deal with this problem, a novel dual periodic event-triggered mechanism is first proposed, in which a saturation-assisted periodic event-trigger and a complemental periodic event-trigger work synergistically to screen data more efficiently under the input saturation constraint. In addition, considering the various disturbances in the environment, a more general mixed H∞ and passive performance is introduced to describe the disturbance attenuation level. Based on the Lyapunov-Krasovskii functional, some less conservative consensus criteria are obtained for the multi-agent systems. In addition, under different input saturation constraints, the relationship between the disturbance attenuation level and the data transmission rate is explored. After that, a particle swarm optimization algorithm is a first attempt to estimate and enlarge the region of asymptotic consensus. Finally, an example is given to verify the effectiveness and superiority of our proposed method.

Knockdown of POLQ interferes the development and progression of hepatocellular carcinoma through regulating cell proliferation, apoptosis and migration.

BACKGROUND: DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs), whose function in hepatocellular carcinoma has not been investigated. METHODS: In the present study, both the data collected from the Cancer Genome Atlas (TCGA) and our group's results showed higher POLQ expression in HCC tissues than the para-cancerous tissues, which was associated with higher malignancy and poor prognosis. POLQ knockdown HCC cell model (shPOLQ) was constructed along with the corresponding negative control (shCtrl) through lentivirus infection for loss-of-function study. RESULTS: We found that, upon knockdown of POLQ, the proliferation and migration of HCC cells decreased and apoptosis percentage increased. Moreover, the percentage of cells in G2 phase significantly increased in shPOLQ group compared with shCtrl group. Xenografts in mice grafted with shPOLQ cells grew much slower than that transplanted with shCtrl cells, and expressed lower Ki67 level. Furthermore, an apoptosis-related signaling array was used to explore the involvement of downstream signaling pathways, suggesting the enhanced phosphorylation of HSP27 and JNK, and the de-activation of mTOR, PRAS40, ERK1/2 and STAT3 pathways. CONCLUSIONS: Collectively, our study revealed that POLQ may participate in the development of HCC, depletion of which may be a promising treatment strategy for HCC.

Comparison and development of machine learning tools for the prediction of chronic obstructive pulmonary disease in the Chinese population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health problem and cause of mortality worldwide. However, COPD in the early stage is usually not recognized and diagnosed. It is necessary to establish a risk model to predict COPD development. METHODS: A total of 441 COPD patients and 192 control subjects were recruited, and 101 single-nucleotide polymorphisms (SNPs) were determined using the MassArray assay. With 5 clinical features as well as SNPs, 6 predictive models were established and evaluated in the training set and test set by the confusion matrix AU-ROC, AU-PRC, sensitivity (recall), specificity, accuracy, F1 score, MCC, PPV (precision) and NPV. The selected features were ranked. RESULTS: Nine SNPs were significantly associated with COPD. Among them, 6 SNPs (rs1007052, OR = 1.671, P = 0.010; rs2910164, OR = 1.416, P < 0.037; rs473892, OR = 1.473, P < 0.044; rs161976, OR = 1.594, P < 0.044; rs159497, OR = 1.445, P < 0.045; and rs9296092, OR = 1.832, P < 0.045) were risk factors for COPD, while 3 SNPs (rs8192288, OR = 0.593, P < 0.015; rs20541, OR = 0.669, P < 0.018; and rs12922394, OR = 0.651, P < 0.022) were protective factors for COPD development. In the training set, KNN, LR, SVM, DT and XGboost obtained AU-ROC values above 0.82 and AU-PRC values above 0.92. Among these models, XGboost obtained the highest AU-ROC (0.94), AU-PRC (0.97), accuracy (0.91), precision (0.95), F1 score (0.94), MCC (0.77) and specificity (0.85), while MLP obtained the highest sensitivity (recall) (0.99) and NPV (0.87). In the validation set, KNN, LR and XGboost obtained AU-ROC and AU-PRC values above 0.80 and 0.85, respectively. KNN had the highest precision (0.82), both KNN and LR obtained the same highest accuracy (0.81), and KNN and LR had the same highest F1 score (0.86). Both DT and MLP obtained sensitivity (recall) and NPV values above 0.94 and 0.84, respectively. In the feature importance analyses, we identified that AQCI, age, and BMI had the greatest impact on the predictive abilities of the models, while SNPs, sex and smoking were less important. CONCLUSIONS: The KNN, LR and XGboost models showed excellent overall predictive power, and the use of machine learning tools combining both clinical and SNP features was suitable for predicting the risk of COPD development.

A Linguistic Hierarchy Model with Self-Confidence Preference Relations and Its Application in Co-Regulation of Food Safety in China.

Linguistic preference relations are widely used by decision makers to elicit their preferences over alternatives in the Group Decision Making (GDM) process. Recent studies have shown that self-confidence, as an important human psychological behavior, has an important influence on decision-making results. However, multiple self-confidence levels of decision makers are seldom considered in the linguistic preference relation. Meanwhile many real-word decision-making problems are analyzed in a hierarchical structure, in which a complicated problem can be divided into several easier comprehended sub-problems. Hence, this paper aims at designing a linguistic hierarchy model with self-confidence preference relation (LHM-SCPR) to discuss complex GDM problems in a hierarchical structure. In the SC-LPR, each element contains two components, the first one is the preference value between pairs of alternatives, and the second one that is defined on a linguistic term set represents decision maker's self-confidence level associated to the first component. Meanwhile, a nonlinear programming model is proposed to derive individual preference vector from SC-LPR. Then, we apply LHM-SCPR in co-regulation of food safety to present the validity of this method, and find that improving the participation skills regarding co-regulation of food safety is the most pressing task. Finally, detailed comparative analysis and discussion are presented to verify the validity of the proposal.

Trillium tschonoskii maxim extract attenuates abnormal Tau phosphorylation.

Large-scale epidemiological studies have found that hyperhomocysteinemia is a powerful, independent risk factor for Alzheimer's disease. Trillium tschonoskii maxim is a traditional Chinese medicine that is used to promote memory. However, scientific understanding of its mechanism of action is limited. This report studied the potential neuroprotective effects of Trillium tschonoskii maxim extract against homocysteine-induced cognitive deficits. Rats were intravenously injected with homocysteine (400 µg/kg) for 14 days to induce a model of Alzheimer's disease. These rats were then intragastrically treated with Trillium tschonoskii maxim extract (0.125 or 0.25 g/kg) for 7 consecutive days. Open field test and Morris water maze test were conducted to measure spontaneous activity and learning and memory abilities. Western blot assay was used to detect the levels of Tau protein and other factors involved in Tau phosphorylation in the hippocampus. Immunohistochemical staining was used to examine Tau protein in the hippocampus. Golgi staining was applied to measure hippocampal dendritic spines. Our results demonstrated that homocysteine produced learning and memory deficits and increased levels of Tau phosphorylation, and diminished the activity of catalytic protein phosphatase 2A. The total number of hippocampal dendritic spines was also decreased. Trillium tschonoskii maxim extract treatment reversed the homocysteine-induced changes. The above results suggest that Trillium tschonoskii maxim extract can lessen homocysteine-induced abnormal Tau phosphorylation and improve cognitive deterioration such as that present in Alzheimer's disease.

A low serum Tat-interacting protein 30 level is a diagnostic and prognostic biomarker for hepatocellular carcinoma.

The present study aimed to evaluate the diagnostic and prognostic value of Tat-interacting protein 30 (HTATIP2/TIP30) levels alone and in combination with α-fetoprotein (AFP) for the evaluation of hepatocellular carcinoma (HCC) patients. ELISA and immunohistochemical measurements on the serum and tissue of HTATIP2/TIP30 protein from HCC patients and normal controls were made. Receiver operating characteristic (ROC) curve analyses of AFP and HTATIP2/TIP30 were performed, as well as logistic regression analysis of APF combined with HTATIP2/TIP30. Log-rank analysis was used to correlate the prognosis with various levels of HTATIP2/TIP30. HTATIP2/TIP30 levels were significantly lower in the HCC group compared with the control group (4.50±2.63 vs. 9.50±2.04 ng/ml, P<0.001). ROC analysis revealed an optimal cut-off point at 7.27 ng/ml HTATIP2/TIP30 for separating the HCC from the control groups. The sensitivity and specificity were 84.6 and 93.7% (P<0.001), respectively. ROC areas of HTATIP2/TIP30 (0.928, P<0.001) were significantly higher than those for AFP (P<0.001). The area under the curve of the HTATIP2/TIP30 and AFP combination was 0.950 (P<0.001). Log-rank tests revealed that the recurrence-free survival time of the group with HTATIP2/TIP30>5.71 ng/ml was significantly higher than that of the control group (P<0.001). This is the first study to demonstrate that HTATIP2/TIP30 levels in serum may be an effective biomarker for the diagnosis and prognosis of HCC.

Glucose-6-Phosphate Isomerase (G6PI) Mediates Hypoxia-Induced Angiogenesis in Rheumatoid Arthritis.

The higher level of Glucose-6-phosphate isomerase (G6PI) has been found in both synovial tissue and synovial fluid of rheumatoid arthritis (RA) patients, while the function of G6PI in RA remains unclear. Herein we found the enrichment of G6PI in microvascular endothelial cells of synovial tissue in RA patients, where a 3% O2 hypoxia environment has been identified. In order to determine the correlation between the high G6PI level and the low oxygen concentration in RA, a hypoxia condition (~3% O2) in vitro was applied to mimic the RA environment in vivo. Hypoxia promoted cellular proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and induced cell migration and angiogenic tube formation of human dermal microvascular endothelial cells (HDMECs), which were accompanied with the increased expression of G6PI and HIF-1α. Through application of G6PI loss-of-function assays, we confirmed the requirement of G6PI expression for those hypoxia-induced phenotype in RA. In addition, we demonstrated for the first time that G6PI plays key roles in regulating VEGF secretion from RASFs to regulate the hypoxia-induced angiogenesis in RA. Taken together, we demonstrated a novel pathway regulating hypoxia-induced angiogenesis in RA mediated by G6PI.

The Ankyrin Repeat Domain 49 (ANKRD49) Augments Autophagy of Serum-Starved GC-1 Cells through the NF-κB Pathway.

The ankyrin repeat domain 49 (ANKRD49) is an evolutionarily conserved protein highly expressed in testes. However, the function of ANKRD49 in spermatogenesis is unknown. In this study, we found that ANKRD49 resides primarily in nucleus of spermatogonia, spermatocytes and round spermatids. ANKRD49 overexpression augments starvation-induced autophagy in male germ GC-1 cells whereas shRNA knockdown of ANKRD49 attenuates the autophagy. Inhibition of NF-κB pathway by its inhibitors or p65 siRNA prevents the ANKRD49-dependent autophagy augmentation, demonstrating that ANKRD49 enhances autophagy via NF-κB pathway. Our findings suggest that ANKRD49 plays an important role in spermatogenesis via promotion of autophagy-dependent survival.

Decreased expression of alpha-enolase inhibits the proliferation of hypoxia-induced rheumatoid arthritis fibroblasts-like synoviocytes.

OBJECTIVES: To investigate the effect of decreased alpha-enolase (ENO1) expression on rheumatoid arthritis fibroblasts-like synoviocytes (RA-FLSs) proliferation in response to hypoxia, and elucidate the possible mechanisms involved. METHODS: RA-FLSs and osteoarthritis fibroblasts-like synoviocytes (OA-FLSs) were cultured in tri-gas incubators with different oxygen concentrations (3% O2, 7% O2, and 21% O2). 3% O2 (hypoxia) and 7% O2 conditions simulated intra-articular oxygen concentrations as observed in RA and healthy individual, respectively. 21% O2 represented oxygen condition for normal cell culture. ENO1-knockdown FLSs were established using ENO1-siRNA. The expression level of ENO1 was detected using reverse transcription polymerase chain reaction or RT-PCR and Western blot. Proliferation and apoptosis of RA-FLSs and OA-FLSs were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium or MTS assay and flow cytometry, respectively. Western blot analysis was used to detect key proteins involved in apoptosis. RESULTS: ENO1 gene expression was remarkably upregulated, as well as its translation into protein, in RA-FLSs and OA-FLSs that were cultured in 3% O2 concentration. RA-FLSs and OA-FLSs that were cultured under hypoxic conditions hyperproliferated compared with similar cells under normaxic conditions. Neither 7% O2 nor 21% O2 condition had any significant effect on ENO1 expression. ENO1-siRNA-transfected FLSs, but not control-siRNA FLSs, showed markedly decreased proliferation. Additionally, ENO1 expression was found to promote significantly higher expression levels of the anti-apoptotic proteins Bcl-2, surviving, and cyclinB1, but inhibited the expression of cleaved caspase3. CONCLUSION: ENO1 may be crucial in the regulation of the proliferation and survival of synovial fibroblasts.

Effects of Bushen Huoxue formula on the learning and memory function and the cerebral neurotransmitters in diabetic mice.

OBJECTIVE: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice. METHODS: Forty ICR mice were randomized into the normal control group, model group, Nimotop group and Chinese medicine group, 10 mice in each group. Tail intravenous injection of alloxan was applied to prepare diabetic model. Four weeks later, intragastric administration of Bushen Huoxue Formula for the Chinese medicine group, Nimotop for the Nimotop group, and isometric distilled water for the other two groups were respectively given for 8 weeks. The changes in the blood sugar level were observed; the learning and memory function was detected by Morris labyrinth test; and the contents of norepinephrine (NE), dopamine (DA), 5-hydroxyltryptamine (5-HT) and 5-hydroxyl indole acetic acid (5-HIAA) in cerebral cortex were determined in mice of all the groups. RESULTS: The blood sugar levels in the diabetic model mice significantly increased as compared with those of the normal control group determined 72 h and 12 weeks later (P < 0.05 or P < 0.01). Latencies for Morris labyrinth test in the Nimotop group and the Chinese medicine group were significantly shortened as compared with that in the model group (P < 0.01). The contents of cortical NE in the Chinese medicine group was significantly higher than that in the model group (P < 0.01). CONCLUSION: Bushen Huoxue Formula can improve the learning and memory function in the diabetic mice, and the mechanism is possibly related with change of the cortical NE content.