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BACKGROUND An increased amount of Fusobacterium nucleatum (F. nucleatum) is frequently detected in the gastric cancer-associated microbiota of the Taiwanese population. F. nucleatum is known to exert cytotoxic effects and play a role in the progression of colorectal cancer, though the impact of F. nucleatum colonization on gastric cancer cells and patient prognosis has not yet been examined. AIM To identify F. nucleatum-dependent molecular pathways in gastric cancer cells and to determine the impact of F. nucleatum on survival in gastric cancer. METHODS Coculture of F. nucleatum with a gastric cancer cell line was performed, and changes in gene expression were investigated. Genes with significant changes in expression were identified by RNA sequencing. Pathway analysis was carried out to determine deregulated cellular functions. A cohort of gastric cancer patients undergoing gastrectomy was recruited, and nested polymerase chain reaction was performed to detect the presence of F. nucleatum in resected cancer tissues. Statistical analysis was performed to determine whether F. nucleatum colonization affects patient survival. RESULTS RNA sequencing and subsequent pathway analysis revealed a drastic interferon response induced by a high colonization load. This response peaked within 24 h and subsided after 72 h of incubation. In contrast, deregulation of actin and its regulators was observed during prolonged incubation under a low colonization load, likely altering the mobility of gastric cancer cells. According to the clinical specimen analysis, approximately one-third of the gastric cancer patients were positive for F. nucleatum, and statistical analysis indicated that the risk for colonization increases in late-stage cancer patients. Survival analysis demonstrated that F. nucleatum colonization was associated with poorer outcomes among patients also positive for Helicobacter pylori (H. pylori). CONCLUSION F. nucleatum colonization leads to deregulation of actin dynamics and likely changes cancer cell mobility. Cohort analysis demonstrated that F. nucleatum colonization leads to poorer prognosis in H. pylori-positive patients with late-stage gastric cancer. Hence, combined colonization of F. nucleatum and H. pylori is a predictive biomarker for poorer survival in late-stage gastric cancer patients treated with gastrectomy.

Background this article investigates the association between life satisfaction and disability-free survival, and explores the roles of chronic diseases and healthy lifestyle in this association. Method a cohort of 2,116 functionally independent adults aged ≥60 was followed up to 12 years. At baseline, life satisfaction was assessed with the Life Satisfaction Index A (LSI-A). Disability-free survival was defined as the survival till the first occurrence of either death, dementia or physical disability. Information on lifestyle factors was collected via questionnaire. Chronic diseases were ascertained through clinical examinations at baseline and each follow-up. Data were analysed using Cox proportional hazard regression models and Laplace regression. Results over follow-up, 1,121 participants died, developed dementia, or became disabled. High LSI-A versus Low LSI-A had a lower risk of death, dementia and physical disability (hazard ratio [HR] 0.79, 95% confidence intervals [CI] 0.67–0.94), and had a longer disability-free period by 1.73 (95% CI 0.18–3.32) years. In mediation analysis, accumulation of chronic diseases mediated 17.8% of the association between LSI-A and disability-free survival. In joint effect analysis, participants with high LSI-A and a favourable lifestyle profile had a HR of 0.53 (95% CI 0.41–0.69) for the composite endpoint, and lived 3.2 (95% CI 1.35–5.11) disability-free years longer than those with low life satisfaction and an unfavourable lifestyle profile. Discussion high life satisfaction is independently associated with longer disability-free survival. This association is partially mediated by a lower burden of chronic diseases and is reinforced by healthy lifestyle.

Background: Although the etiology of Hashimoto's thyroiditis (HT), a common autoimmune endocrine disease, is unknown, studies suggest a potential association with genetic factors and environmental conditions inducing excessive iodine intake. Additionally, HT patients have a high risk of papillary thyroid cancer (PTC), which is probably related to the chronic inflammation and autoimmune pathologic process occurring in HT, as it is thought to be associated with neoplastic transformation. Methods: Bioinformatics approaches can identify differentially expressed genes (DEGs) and analyze DEG functions in diseases. R software was used in this study to identify DEGs in HT and PTC using data in Gene Expression Omnibus (GEO). The online tools DAVID, Reactome, and AmiGO were employed for annotation, visualization, and integration of DEGs related to HT and PTC, and the STRING database and Cytoscape software were applied to predict and visualize protein-protein networks (PPIs) for DEG-encoded proteins. Coexpressed DEGs in HT and PTC were validated by reverse transcription PCR (RT-PCR). Results: In total, 326, 231, and 210 DEGs in HT specimens and samples of central PTC and PTC invasive areas, respectively, were detected. According to the PPI network, PTPN6, HLA-A, C3AR1, LCK and ITGB2 are hub genes among HT-DEGs, whereas FN1, CDH2, SERPINA1, and CYR61 are PTC-DEG hub genes. The shared DEGs LTF and CCL21 were validated by RT-PCR. Both bioinformatics and RT-PCR analyses showed LTF and CCL21 to be upregulated in HT tissues and downregulated in PTC tissues. Conclusions: We identified that expression of LTF and CCL21 are significantly different in HT and PTC, suggesting an underlying association between HT and PTC.

INTRODUCTION: The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies.METHODS: Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies.RESULTS: The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12).CONCLUSIONS: A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.

The clinical efficacy of ticagrelor versus clopidogrel has not been replicated in East Asian populations. The pronounced bleeding risk with ticagrelor was of concern given the increased bleeding tendency in Asian populations. This study evaluated efficacy and safety of ticagrelor versus clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI) in the entire Taiwan. We used the Taiwan National Health Insurance Research Database to identify 6203 patients aged ≥ 20 years with NSTEMI hospitalization and prescription of dual antiplatelets at discharge between January 2014 and December 2014. Cohorts of ticagrelor and clopidogrel were matched 1:1 based on propensity score matching to balance baseline covariates. The primary composite efficacy endpoints included death from any cause, non-fatal myocardial infarction, and non-fatal stroke. The secondary efficacy endpoints were the individual components. The primary safety endpoint was major bleeding requiring hospitalization. The incidence of primary efficacy endpoint was 20.3% in the ticagrelor users and 20.7% in the clopidogrel users (adjusted HR 0.94; 95% CI 0.73–1.22), with the median (interquartile range, IQR) follow-up period of 5.2 (2.3–8.5) months. The incidence of primary safety endpoint was 2.3% in the ticagrelor users and 3.2% in the clopidogrel users (adjusted HR 0.67; 95% CI 0.33–1.35). Regarding the secondary efficacy endpoint, patients treated with ticagrelor had significantly lower incidence of stroke (adjusted HR 0.44; 95% CI 0.21–0.94; p = 0.033). In this nationwide Taiwanese cohort of NSTEMI, treatment with ticagrelor after discharge, as compared to clopidogrel, had similar rates of ischemic composite events and major bleeding. Nevertheless, the median follow-up time was only 5.2 months, and the reduced stroke events with ticagrelor compared to clopidogrel needs further verification.

Background Pyruvate carboxylase (PC) is an important anaplerotic enzyme in the tricarboxylic acid cycle (TCA) in cancer cells. Although PC overexpression has been observed in thyroid cancer (TC), the mechanisms involved in the carcinogenic effects of PC are still unclear. Methods Bioinformatics analysis and clinical specimens were used to analyze the relationship of PC expression with clinicopathological variables in TC. Fatty acid synthesis was monitored by LC/MS, Nile red staining, and triglyceride analysis. Mitochondrial oxygen consumption was evaluated by the Seahorse XF Mito Cell Stress Test. The correlation of PC with FASN and SREBP1c was assessed by qRT-PCR and IHC in 38 human TC tissues. Western blotting was used to evaluate the protein expression of PC, FASN, and SREBP1c and members of the AKT/mTOR and EMT pathways in TC cell lines. Wound-healing, CCK-8, and Transwell assays and a nude mouse xenograft model were used to verify the regulatory effects of PC and SREBP1c on thyroid tumor cell proliferation, migration and invasion. Results We demonstrated that PC increased fatty acid synthesis, which then promoted TC progression and metastasis. Analysis of GEO data showed that the overexpression of PC in papillary thyroid cancer (PTC) was associated with PTC invasion and the fatty acid synthesis pathway. Analysis of clinical tissue specimens from PTC patients revealed that PC was more highly expressed in specimens from PTC patients with lymph node metastasis than in those from patients without metastasis. Multiple genes in the fatty acid synthesis signaling pathway, including FASN and SREBP1c, were downregulated in PC-knockdown TC cells compared to control cells. Lipid levels were also decreased in the PC-knockdown TC cells. Moreover, the ability of cells to grow, invade, and metastasize was also suppressed upon PC knockdown, suggesting that PC-mediated lipogenesis activation increases the aggressiveness of TC cells. In addition, PC was found to activate the AKT/mTOR pathway, thus improving FASN-mediated de novo lipogenesis in TC cells by upregulating SREBP1c expression. Studies in a nude mouse xenograft model showed that PC knockdown decreased tumor weight, but this effect was attenuated by forced expression of SREBP1c. Conclusions Our results demonstrate that PC is strongly involved in the tumor aggressiveness of TC via its stimulation of fatty acid synthesis.

Arbutin is a well-known tyrosinase inhibitor that prevents the formation of melanin through the inhibition of tyrosinase. Therefore, it has been widely used as a cosmetic skin-lightening agent. Arbutin is able to scavenge free radicals within cells and previous studies have found that it also exhibited useful activities for the treatment of diuresis, bacterial infections, and cancer, as well as anti-inflammatory and anti-tussive activities. This study analyzed the effects of arbutin on streptozotocin (STZ)-induced diabetes mellitus in a murine model. Healthy male adult C57BL/6 mice (7 weeks old) were randomly allocated into one of the following three groups of six animals: Normal control with no STZ administration, STZ-induced diabetes, and STZ-induced diabetes treated with 0.3 g/kg/day of arbutin. After 12 days, the levels of insulin, C-peptide, and HbA1c were measured in serum, and the expression and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were analyzed in pancreatic tissues by western blotting. Arbutin was found to significantly inhibit the increase in blood glucose and the loss of body weight in diabetic mice. Arbutin increased plasma insulin levels in mice with STZ-induced diabetes, whereas there was no detection of insulin in untreated diabetic mice. In addition, there was an increased expression and activity of SOD, CAT, and GPx in diabetic mice treated with arbutin. This investigation demonstrated that arbutin possesses antioxidant activities and can alleviate symptoms of type-1 diabetes mellitus (T1DM) in mice.

Background Most of acute pancreatitis (AP) are mild and self‐limiting, however, 15%–20% of patients develop severe acute pancreatitis (SAP) or moderately acute pancreatitis (MSAP) with local or systemic complications. Infection complications (ICs) result in 40%–70% morbidity and high mortality rates among SAP and MSAP patients. It is more important to early recognize of ICs of MSAP or SAP. Several studies have indicated that serum soluble programmed cell death protein (sPD‐1) or programmed cell death 1 ligand (sPD‐L1) levels were higher in patients with severe sepsis than in healthy volunteers and have a predictive capacity for mortality. However, the role of serum sPD‐1/sPD‐L1 in AP remains unclear. This study aimed to investigate whether the ICs of AP patients is associated with their sPD‐1 and sPD‐L1 levels, which were determined via enzyme‐linked immunosorbent assay of peripheral blood samples from 63 MSAP and SAP patients and 30 healthy volunteers. Results The serum sPD‐1 levels in AP patients on Days 1, 3, and 10 after onset were significantly increased in a time‐dependent manner compared with that in healthy volunteers. Moreover, the AP patients with ICs had significantly higher serum sPD‐1 levels than the AP without ICs. While serum sPD‐L1 levels in AP were similar to that in healthy volunteers. Besides, serum levels of sPD‐1/sPD‐L1 were negatively correlated with circulating lymphocytes. Univariate and multivariate regression analyses showed that the upregulated serum sPD‐1 level was an independent risk factor for ICs in AP. The area under the receiver operating characteristics curve indicated that combination with Acute Physiology and Chronic Health Evaluation II score and serum sPD‐1 level had a high accuracy in predicting ICs in AP. Conclusion Serum sPD‐1/sPD‐L1 may be involved in the immunosuppressive process in AP. Moreover, the serum sPD‐1 level may be an independent risk factor for predicting ICs in AP patients., This study investigated whether the immune status and infection complications of acute pancreatitis (AP) patients are associated with their serum soluble programmed cell death protein (sPD‐1) or programmed cell death 1 ligand (sPD‐L1) levels. We believe that our study makes a significant contribution to the literature because it clearly demonstrates that serum sPD‐1/sPD‐L1 may be involved in the immunosuppressive process in AP, and the serum sPD‐1 level may be an independent risk factor for predicting ICs in AP patients.

Background/Purpose: Orthopaedic Trauma Association (OTA) C-type distal femoral fractures can be very challenging to treat effectively. While locked plating is widely used in the complex distal femoral fracture, failure of locked plate fixation is not uncommon.First, we tried to determine the risk factor related to early failure of multiplanar OTA C-type fracture in the distal femur after fixation with lateral locked plate.Second, we tried to provide a strategy for surgeons to prevent pitfalls of early failure in the complex distal femoral fractures treated with lateral locked plating. Methods: We retrospectively reviewed 44 adults with OTA C-type fractures of the distal femur treated with locked plate fixation between 2010 and 2016 at Tri-Service General Hospital. Average length of follow-up was 27.6 months (range, 12–54 months). Univariate and multivariate logistic regression were used to determine the association of variables on early failure of fixation. A p-value < 0.05 in univariate and multivariate analyses were considered significant. Results: There were six patients experiencing early failure, and the early failure rate was 13.6%. The risk factors associated with early failure of complex distal femoral fracture identified by univariate analysis included sagittal oblique fracture pattern, longer working length and post-operative sagittal malalignment (odds ratio [OR] and 95% confidence intervals [CI]: 90.00 (6.85–1183.33), 0.55 (0.31–0.98) and 8.63 (1.077–69.075) respectively). The multivariate analysis showed only sagittal oblique fracture pattern was associated with early failure [OR: 52.348 (3.06–895.23)]. Conclusion: Sagittal oblique fracture was more likely to result in early postoperative failure. Early recognition of the fracture pattern should be considered to avoid catastrophic results.

Context The traditional medicine 2036 Specialty-Qiangxin recipe (2036S-QXR) has been widely used in China to improve cardiac function, prevent stroke, and strengthen the immune system. However, its long-term toxicity remains unknown. Objective The present study evaluates the long-term toxicity of 2036S-QXR in rats. Materials and methods 2036S-QXR (0.6, 1.2, and 2.4 g/kg body weight per day) was orally administered for 26 weeks to Wistar rats, while the rats in the control group received distilled water. The effects on urinary, hematological, biochemical, and histopathological parameters were investigated during the study period. Results No significant changes in all tested parameters were observed in the 0.6 and 1.2 g/kg groups, compared with the control group (p 0.05). Several cases displayed the presence of urine protein (3/7 males and 3/7 females) and mild lesions in the kidney (10/20) and thymus (5/20) in the 2.4 g/kg group, without significant changes compared with the control group (p > 0.05). Discussion and conclusions The present study shows that 2036S-QXR does not cause long-term toxicity, supporting its therapeutic use. To further determine the optimal doses, future studies should test more doses and include more animals in each group.

Background & Aims Identifying novel and actionable targets in hepatocellular carcinoma (HCC) remains an unmet medical need. TAK1 was originally identified as a transforming growth factor-β–activated kinase and was further proved to phosphorylate and activate numerous downstream targets and promote cancer progression. However, the role of TAK1 in developed HCC progression and targeted therapy resistance is poorly understood. Methods The expression of TAK1 or MTDH in HCC cell lines, tumor tissues, and sorafenib-resistant models was analyzed by in silico analysis, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. In vivo and in vitro experiments were introduced to examine the function of TAK1 or MTDH in HCC and sorafenib resistance using small interfering RNA and pharmacologic inhibitors in combination with or without sorafenib. Co-immunoprecipitation and RNA immunoprecipitation were carried out to determine the binding between TAK1 and FBXW2 or between MTDH and FBXW2 mRNA. Protein half-life and in vitro ubiquitination experiment was performed to validate whether FBXW2 regulates TAK1 degradation. Results Our findings unraveled the clinical significance of TAK1 in promoting HCC and sorafenib resistance. We identified a novel E3 ubiquitin ligase, FBXW2, targeting TAK1 for K48-linked polyubiquitylation and subsequent degradation. We also found that MTDH contributes to TAK1 up-regulation in HCC and sorafenib resistance through binding to FBXW2 mRNA and accelerates its degradation. Moreover, combination of TAK1 inhibitor and sorafenib suppressed the growth of sorafenib-resistant HCCLM3 xenograft in mouse models. Conclusions These results revealed novel mechanism underlying TAK1 protein degradation and highlighted the therapeutic value of targeting TAK1 in suppressing HCC and overcoming sorafenib resistance.

Stroke is a world-leading disease for causing disability. Brain-computer interaction (BCI) training has been proved to be a promising method in facilitating motor recovery. However, due to differences in each patient’s neural-clinical profile, the potential of recovery for different patients can vary significantly by conducting BCI training, which remains a major problem in clinical rehabilitation practice. To address this issue, the objective of this study is to prognosticate the outcome of BCI training using motor state electroencephalographic (EEG) collected during the first session of BCI tasks, with the aim of prescribing BCI training accordingly. A Convolution Neural Network (CNN) based prognosis model was developed to predict the outcome of 11 stroke patients’ recovery following a 2-week rehabilitation training with BCI. In our study, functional connectivity and power spectrum have been evaluated and applied as the inputs of CNN to regress patients’ recovery rate. A saliency map was used to identify the correlation between EEG channels with the recovery outcome. The performance of our model was assessed using the leave-one-out cross-validation. Overall, the proposed model predicted patients’ recovery with R2 0.98 and MSE 0.89. According to the saliency map, the highest functional connectivity occurred in Fp2/Fpz-AF8, Fp2/F4/F8-P3, P1/PO7-PO5 and AF3-AF4. Our results demonstrated that deep learning method has the potential to predict the recovery rate of BCI training, which contributes to guiding individualized prescription in the early stage of clinical rehabilitation.

Background Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. Method 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. Result Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28−, CD127−, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. Conclusion The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.

OBJECTIVE: To explore the impact of rehabilitation robot training (RRT) on upper limb motor function and daily activity ability in patients with stroke. METHODS: Forty patients meeting the inclusion criteria were randomly divided into the treatment group (TRE) and the control group (CON). Group TRE was trained with an upper limb rehabilitation robot and group CON was trained with traditional occupational therapy. The training time was six weeks, and the upper limb function and daily activities were then assessed. RESULTS: (1) There was no statistical significance in the Fugl-Meyer (FM) score, Wolf Motor Function Test (WMFT) score, and Modified Barthel Index (MBI) score between the two groups before treatment (P > 0.05). (2) After treatment, the FM score, WMFT score, and MBI score were significantly higher than before treatment (P 0.05). CONCLUSIONS: Both RRT and traditional occupational therapy training are useful for the recovery of upper limb motor function and daily life ability in the sub-acute stage of stroke.

The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injury–induced AKI (IRI-AKI). Myofibroblasts underwent apoptosis during renal recovery but one-fifth of them survived in the recovered kidneys on day 28 after IRI-AKI and their cell numbers increased again after day 56. Microarray data showed the distinctive gene expression patterns of qPericytes, activated pericytes (aPericytes, myofibroblasts), and inactivated pericytes (iPericytes) isolated from kidneys before, on day 7, and on day 28 after IRI-AKI. Hypermethylation of the Acta2 repressor Ybx2 during IRI-AKI resulted in epigenetic modification of iPericytes to promote the transition to chronic kidney disease (CKD) and aggravated fibrogenesis induced by a second AKI induced by adenine. Mechanistically, transforming growth factor-β1 decreased the binding of YBX2 to the promoter of Acta2 and induced Ybx2 hypermethylation, thereby increasing α-smooth muscle actin expression in aPericytes. Demethylation by 5-azacytidine recovered the microvascular stabilizing function of aPericytes, reversed the profibrotic property of iPericytes, prevented AKI-CKD transition, and attenuated fibrogenesis induced by a second adenine-AKI. In conclusion, intervention to erase hypermethylation of pericytes after AKI provides a strategy to stop the transition to CKD.

Aims Steroid diabetes mellitus (SDM) is a metabolic syndrome caused by an increase in glucocorticoids, and its pathogenesis is unclear. 18F-FDG PET/CT can reflect the glucose metabolism of tissues and organs under living conditions. Here, PET/CT imaging of SDM and type 2 diabetes mellitus (T2DM) rats was used to visualize changes in glucose metabolism in the main glucose metabolizing organs and investigate the pathogenesis of SDM. Methods SDM and T2DM rat models were established. During this time, PET/CT imaging was used to measure the %ID/g value of skeletal muscle and liver to evaluate glucose uptake. The pancreatic, skeletal muscle and liver were analyzed by immunohistochemistry. Results SDM rats showed increased fasting blood glucose and insulin levels, hyperplasia of islet α and β cells, increased FDG uptake in skeletal muscle accompanied by an up-regulation of PI3Kp85α, IRS-1, and GLUT4, no significant changes in liver uptake, and that glycogen storage in the liver and skeletal muscle increased. T2DM rats showed atrophy of pancreatic islet β cells and decreased insulin levels, significantly reduced FDG uptake and glycogen storage in skeletal muscle and liver. Conclusions The pathogenesis of SDM is different from that of T2DM. The increased glucose metabolism of skeletal muscle may be related to the increased compensatory secretion of insulin. Glucocorticoids promote the proliferation of islet α cells and cause an increase in gluconeogenesis in the liver, which may cause increased blood glucose.

Subarachnoid hemorrhage (SAH) patients’ surgery is performed to prevent extravasation of blood into the subarachnoid space. Cerebral vasospasm (CVS; narrowing of cerebral arteries) occurs following SAH and represents a major cause of associated mortality and morbidity. To improve postsurgery care of SAH patients and their prognosis, the ability to predict CVS onset is critical. We report a long noncoding RNA (lncRNA) signature to distinguish SAH patients with CVS from SAH patients without CVS. Cerebrospinal fluid (CSF) was obtained from SAH patients without CVS (n = 10) and SAH patients with CVS (n = 10). lncRNAs ZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without CVS. We applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients., Graphical Abstract, Cerebral vasospasm (CVS) is a major cause of subarachnoid hemorrhage (SAH) mortality and morbidity. However, the prediction of CVS remains a clinical challenge. Yun-Feng Cui and colleagues report that lncRNAs MALAT1 and LINC01619 can predict CVS occurrence with remarkable precision. This work is a step toward personalized treatment and management of SAH patients.

The feasibility and efficacy of magnetic resonance imaging molecular probe application and pluripotent stem cell-derived neural stem cell (NSC) transplantation for the treatment of hind limb paralysis in mice with cerebral infarction were studied. A model of middle cerebral artery infarction using adult mice was established to stimulate hind limb reactions. After the model was successfully established, the mice were first divided into an experimental group and a control group, with 25 mice in each group. Cultured neural cells were obtained from the cerebral cortex and hippocampus of a mouse 15 days pregnant to prepare pluripotent stem cells. Pluripotent stem cell-derived NSCs were identified by positive expression of Nestin. The experimental group was injected with 1 μL of NSC suspension through the tail vein, and the control group was injected with 1 μL of saline through the tail vein. The neurologic function of mice in each group was scored 1 day, 3 days, 7 days, 14 days, and 28 days after transplantation according to the Garcia 18 subscale. Finally, the differentiation, migration, and integration of pluripotent stem cell-derived NSCs after transplantation were observed using a magnetic resonance imaging molecular probe method. The results showed that the neurologic function scores of the ischemic transplantation group were significantly higher than those of the control group, and the results were significantly different (P0.05). Through research, it was found that after transplantation of pluripotent stem cell-derived NSCs, the transplanted cells migrated and differentiated around the body at 28 days and participated in angiogenesis, and the blood vessels in the infarcted area were obviously proliferated. The NSCs cultured in vitro were transplanted to the small infarction after cerebral infarction. In rats, it plays a positive role in the repair of nerve function in mice with cerebral infarction. NSCs cultured in vitro can survive, migrate, and differentiate in the brain tissue of mouse ischemic models and play a positive role in the repair of neurologic function in mice with cerebral infarction. Magnetic resonance imaging molecular probes have a good adjuvant effect on the use of pluripotent stem cell-derived NSCs to treat hind limb paralysis in mice with cerebral infarction.

The efficacy of basal insulin (BI) for adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) has been well documented by randomized clinical trials. This post hoc analysis of the Observational Registry of Basal Insulin Treatment (ORBIT) study was performed to explore the 6-month dose of BI used in insulin-naïve T2DM patients achieving HbA1c target (7%) and determine the patient characteristics that affect the 6-month dose of BI in the setting of real-world clinics in China.This multicenter observational registry screened 19 894 adult T2DM patients with inadequately controlled hyperglycemia and treated with oral antidiabetic drugs (OADs) in China. Of these patients, 5191 who continued to receive BI after 6 months and achieved HbA1c target were analyzed. Patient characteristics including age, body weight, fasting plasma glucose (FPG), use of OADs, insulin (type and dose), and glycemic control were recorded at baseline and 6-month follow-ups.The 6-month dose of BI needed for effective glycemic control was 0.20 ± 0.08 U/kg/day. High body mass index, high FPG, young age, longer duration of diabetes or OAD treatment, a greater number of OADs at baseline, and allocation to detemir and glargine were significant independent predictors for high dose of BI at 6 months.This post hoc analysis of the ORBIT registry provides key information on the 6-month dose of BI needed for effective glycemic control in Chinese T2DM patients. Furthermore, it identified crucial patient characteristics that are significant determinants of the dose of BI in a real-world setting.背景: 基础胰岛素(BI)对2型糖尿病(T2DM)患者血糖控制的有效性已被随机对照临床试验所证实。这项来自ORBIT研究的事后分析旨在探讨既往未接受胰岛素治疗的中国T2DM患者, 在临床真实世界中接受基础胰岛素治疗6个月后, HbA1c达标(7%)患者的基础胰岛素剂量及其相关特征。 方法: ORBIT研究在中国采用多中心观察性研究方法, 共筛选入组19894例接受口服降糖药(OAD)治疗但血糖控制不佳的2型糖尿病患者。本研究对其中5191例持续接受BI治疗6个月且HbA1c达标(7%)的患者进行了分析。收集的患者特征包括基线和随访6个月时的年龄, 体重, 空腹血浆血糖(FPG), OAD使用情况, 胰岛素的类型和剂量以及血糖控制情况。 结果: 治疗6个月时血糖达标患者的BI剂量为0.20±0.08U/kg/d。高体重指数, 高FPG, 年龄小, 糖尿病病程或OAD治疗时间较长, 基线OAD种类多, 接受地特胰岛素或甘精胰岛素治疗是6个月时较高BI剂量的独立预测因素。 结论: 这项ORBIT研究的事后分析提供了启动基础胰岛素治疗6个月的中国2型糖尿病患者血糖控制达标所需BI剂量的关键信息。此外, 该研究明确了在临床真实世界中影响基础胰岛素剂量的患者特征。.

The clavicle hook plate has been commonly used to treat distal clavicle fractures and acromioclavicular (AC) joint dislocations; however, midshaft clavicle fracture at the medial end of the hook plate remains an underestimated complication. We aimed to discover the risk factors for this complication and the influence of these risk factors on patients and to suggest preventive surgical techniques. We retrospectively reviewed the records of 150 patients with acute distal clavicle fractures or acute AC joint dislocations treated by internal fixation with a clavicle hook plate. The patient demographics, the occurrence of midshaft clavicle fracture at the medial end of the hook plate, and functional outcomes were analyzed. The functional outcomes were evaluated with the American Shoulder and Elbow Surgeons (ASES) Shoulder Score and grading of the Constant shoulder score after the hook plate was removed. In total, 17 patients had complicating midshaft clavicle fractures at the medial end of the hook plate. Elderly patients had a higher risk of developing this complication than young patients. The odds ratio was 4.4 (p

Osteosarcoma (OSA) is the most common type of cancer that originates in the bone and usually occurs in young children. OSA patients were treated with neoadjuvant chemotherapy and surgery, and the results were disappointing. Marine antimicrobial peptides (AMPs) have been the focus of antibiotic research because they are resistant to pathogen infection. Piscidin-1 is an AMP from the hybrid striped bass (Morone saxatilis × M. chrysops) and has approximately 22 amino acids. Research has shown that piscidin-1 can inhibit bacterial infections and has antinociception and anti-cancer properties; however, the regulatory effects of piscidin-1 on mitochondrial dysfunction in cancer cells are still unknown. We aimed to identify the effects of piscidin-1 on mitochondrial reactive oxygen species (mtROS) and apoptosis in OSA cells. Our analyses indicated that piscidin-1 has more cytotoxic effects against OSA cells than against lung and ovarian cancer cells; however, it has no effect on non-cancer cells. Piscidin-1 induces apoptosis in OSA cells, regulates mtROS, reduces mitochondrial antioxidant manganese superoxide dismutase and mitochondrial transmembrane potential, and decreases adenosine 5′-triphosphate production, thus leading to mitochondrial dysfunction and apoptosis. The mitochondrial antioxidant, mitoTempo, reduces the apoptosis induced by piscidin-1. Results suggest that piscidin-1 has potential for use in OSA treatment.

Perfluorooctansulfonate (PFOS) is a persistent organic pollutant that has attracted a great deal of attention due to toxic effects such as its lipid metabolism-disrupting potential. Exposure to PFO...

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

We present an 11-year-old male child without any underlying disease. He was admitted to the emergency room after having felt severe pain in his right knee on kicking the ground while falling down earlier that day. Radiography showed an avulsion fracture of the lower pole of the patella and a high-riding patella. At the next day after the injury, we performed open reduction and internal fixation surgery. After surgery, the recovery of the patient was good.

A common finding from both the regulatory compliance and motor-carrier safety literatures is that larger firms are more compliant with safety rules than smaller firms. However, complementary yet alternative explanations have been advanced to explain this empirical regularity. Some scholars argue larger firms' greater resource endowments allow them to make more investments to ensure safety compliance. Other scholars argue larger firms have more incentive to operate in compliance with safety rules because they have more brand equity at stake and are more exposed to regulatory enforcement. As these explanations suggest different policy implications, identifying findings uniquely consistent with one or both mechanisms is important to further efforts to improve carriers' safety compliance. This article leverages archival motor-carrier safety data and estimates different econometric models designed to isolate effects that are uniquely consistent with these alternative mechanisms. The results provide evidence uniquely consistent with each mechanism. This article concludes by explaining theoretical contributions, detailing managerial implications, and offering policy suggestions.

New findings What is the central question of this study? Does regular exercise have benefits with regard to the neurocognitive problems related to obesity and are regular-exercise-induced neurocognitive changes associated with changes in the levels of metabolic/inflammatory biomarkers? What is the main finding and its importance? Although obese individuals with regular exercise showed higher C-reactive protein levels as compared to the healthy-weight individuals, only the obese individuals with a sedentary lifestyle showed deviant neurocognitive performance and higher metabolic and tumour necrosis factor-α levels. The P3 amplitude was correlated with the levels of leptin in the obese individuals with regular activity, implicating that the potential mechanism of neurocognitive facilitation as a result of regular exercise could be reduced serum leptin levels. Abstract Obesity has been shown to be highly associated with deterioration in executive functions, elevated energy metabolic indices and low-grade systemic inflammation. Exercise has the capacity to reduce these negative phenomena. This work examined the effect of regular exercise on neurocognitive deficits and metabolic/inflammatory markers in obesity. Fifty-four participants were divided into three groups: healthy-weight (HW), obesity with regular exercise (ORE) and obesity with sedentary lifestyle (OSL), according to their BMI and frequency of exercise. Dual-energy X-ray absorptiometry was applied to assess the whole-body composition of the participants. The assessment included neurocognitive measures during the Posner paradigm test and fasting blood measurements. Relative to the HW group, only the OSL group showed significantly longer reaction times and smaller P3 amplitudes, even when controlling for the cardiorespiratory fitness co-variable. Although the OSL group exhibited a greater N2 amplitude than the HW group, when controlling for cardiorespiratory fitness the difference between the two groups disappeared. The OSL group showed greater levels of metabolic indices (i.e. leptin, insulin and glucose) than the HW group. The three groups had comparable interleukin (IL)-1β and IL-6 levels. However, the ORE and OSL groups showed higher levels of C-reactive protein than the HW group. The OSL group exhibited higher tumour necrosis factor-α levels than the HW and ORE groups. P3 amplitude was negatively correlated with the levels of leptin in the ORE group. Individuals with obesity can still obtain advantages with regard to neurocognitive and metabolic/inflammatory indices through engaging in regular exercise, possibly due to reduced serum leptin levels.

Objectives Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking‐related, and alcohol‐related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. Methods The psychosocial factors and cancer incidence (PSY‐CA) consortium was established involving experts in the field of (psycho‐)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two‐stage individual participant data (IPD) meta‐analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta‐analyses will be performed on the risk estimates (stage 2). Conclusion PSY‐CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta‐analyses., Psychosocial factors and cancer incidence (PSY‐CA) consortium endeavor to understand the role of several different psychosocial factors—including depression and anxiety—in the onset of cancer. The study will employ the use of individual participant data meta‐analyses, combining results from several large, international cohorts with longitudinal designs. Furthermore, PSY‐CA aims to elucidate the role of health behaviors in the relationship between psychosocial factors and cancer risk.

Quantitative studies of the multiple factors influencing the mountain-mass effect, which causes higher temperatures in mountainous than non-mountainous regions, remain insufficient. This study estimated the air temperature in the Yellow River Basin, which spans three different elevation ranges, using multi-source data to address the uneven distribution of regional meteorological stations. The differences in mountain-mass effect for different geomorphic regions at the same altitude were then compared. The Manner–Kendall nonparametric test was used to analyse time series changes in temperature. Moreover, we employed the geographically weighted regression (GWR) model, with MODIS land-surface and air-temperature data, station-based meteorological data, vertical temperature gradients corresponding to the 2000–2015 period, and elevation data, to estimate the correlation between monthly mean surface temperature and air temperature in the Yellow River Basin. The following major results were obtained. (1) The GWR method and ground station-based observations enhanced the accuracy of air-temperature estimates with an error of only ± 0.74°C. (2) The estimated annual variations in the spatial distributions of 12-month average temperatures showed that the upper Tibetan Plateau is characterised by low annual air temperatures with a narrow spatial distribution, whereas north-eastern areas upstream of the Inner Mongolia Plateau are characterised by higher air temperatures. Changes in the average monthly air temperature were also high in the middle and lower reaches, with a narrow spatial distribution. (3) Considering the seasonal variation in the temperature lapse rate, the mountain-mass effect in the Yellow River Basin was very high. In the middle of each season, the variation of air temperature at a given altitude over the Tibetan Plateau was higher than that over the Loess Plateau and Jinji Mountain. The results of this study reveal the unique temperature characteristics of the Yellow River Basin according to its geomorphology. Furthermore, this research contributes to quantifying mountain-mass effects.

In this issue of Diabetes , Wu et al. (1) report that in a high-fat diet/streptozotocin–induced diabetes model, global annexin 1 (ANAX1) deletion exacerbates diabetic nephropathy (DN), as indicated by increased albuminuria and macrophage infiltration, increased glomerular size, mesangial expansion, glomerular basement membrane thickness, and foot process effacement, increased tubulointerstitial injury, and fibrosis. They also detected lipid accumulation and mitochondrial abnormalities in the proximal tubule epithelial cells. RNA-sequencing analysis revealed a role of ANAX1 in lipid metabolism in the HFD/STZ-induced DN mice. Using a human immortalized proximal tubule epithelial cell line, HK-2 cells, they found that ANAX1 knockdown impaired mitochondrial fatty acid oxidation via a FPR2/AMPK/PPARα/CPT2b signaling pathway, leading to reduced intracellular lipid accumulation. ANAX1 knockdown also aggravated the lipid disorders in podocytes. Finally, administration of Ac2-26, an ANAX1 mimetic, ameliorated renal …

Following acute injury to the kidney, macrophages play an important role in recovery of functional and structural integrity, but organ fibrosis and progressive functional decline occur with incomplete recovery. Pro-resolving macrophages are characterized by increased cyclooxygenase 2 (COX-2) expression and this expression was selectively increased in kidney macrophages following injury and myeloid-specific COX-2 deletion inhibited recovery. Deletion of the myeloid prostaglandin E2 (PGE2) receptor, E-type prostanoid receptor 4 (EP4), mimicked effects seen with myeloid COX-2−/− deletion. PGE2-mediated EP4 activation induced expression of the transcription factor MafB in kidney macrophages, which upregulated anti-inflammatory genes and suppressed pro-inflammatory genes. Myeloid Mafb deletion recapitulated the effects seen with either myeloid COX-2 or EP4 deletion following acute kidney injury, with delayed recovery, persistent presence of pro-inflammatory kidney macrophages, and increased kidney fibrosis. Thus, our studies identified a previously unknown mechanism by which prostaglandins modulate macrophage phenotype following acute organ injury and provide new insight into mechanisms underlying detrimental kidney effects of non-steroidal anti-inflammatory drugs that inhibit cyclooxygenase activity.

[Image: see text] Protease-digested lactoferrin fragments often exhibit improved therapeutic properties. However, there are limited studies investigating the anticancer properties of these fragments. The fragment with improved anticancer activities is an attractive alternative to chemotherapeutic drugs—presenting severe side effects. Herein, we report the isolation and characterization of recombinant engineered-lactoferrin (rtHLF4), exhibiting up to 100-fold improved anticancer activity compared to the full-length lactoferrin (flHLF). Further, rtHLF4 exerts its anticancer effect in a shorter duration. Through transcriptomic analysis of various cancer biomarkers, rtHLF4 was found to upregulate various pro-apoptotic markers and downregulate signaling proteins involved in angiogenesis and metastasis. We further determined that rtHLF4 showed no hemolytic activity at high concentrations. We believe that this anticancer protein can be further developed as a cancer treatment.

This study examined the effects of a 12-week floor hockey training program on the motor proficiency, physical fitness, and adaptive development of youths with mild intellectual disabilities (IDs). A total of 54 youths with IDs were divided into two groups: a floor hockey exercise group (EG, n = 27, age, 16.59 ± 0.56 years) and a control group (CG, age, 16.65 ± 0.63 years). The participants in the EG attended sessions of a floor hockey training program 3 times per week over a 12-week period. The CG group maintained their standard activities of daily living. The participants’ scores on the Bruininks–Oseretsky Test of Motor Proficiency, Second Edition, Brockport Physical Fitness Test, and traditional Chinese version of the teacher form of the Adaptive Behavior Assessment System, Second Edition, were obtained before and after the intervention. The results of the study indicate that the 12-week floor hockey training program significantly increased the participants’ scores for most indicators of motor proficiency (p &lt, 0.01), physical fitness (p &lt, 0.01), and adaptive development (p &lt, 0.01). The findings provide evidence that physical activity interventions focusing on floor hockey training are a viable therapeutic option for treating youths with IDs.

The incidence of papillary thyroid carcinoma (PTC) is increasing. Lymph node metastatic status of PTC is a major factor for decision marking of surgery and surgical extend, however, no reliable tool exists for prediction of PTC nodal metastasis, for example, ultrasound cannot qualitatively diagnose and effectively detect central lymph node metastasis (CLNM). Therefore, the development of a new diagnostic biomarker is crucial for CLNM. Metabolic dysregulation is an important factor associated with malignancy and metastasis of tumors. Pyruvate carboxylase (PC) is a major anaplerotic enzyme that catalyzes the carboxylation of pyruvate to form oxaloacetate, which has been suggested to be involved in the tumorigenesis of several cancers, including PTC. This study aimed to explore the role of PC expression in thyroid fine-needle aspiration (FNA) wash-out fluid for predicting CLNM in PTC, and to explore how PC is involved in PTC development. The expression levels of PC in PTC tissues and normal thyroid tissues were first compared based on bioinformatics analysis of public databases, including the Gene Expression Profiling (GEPIA), Oncomine and Gene Expression Omnibus (GEO) databases. Then, the PC mRNA and protein expression levels were measured by RT-PCR and Immunohistochemistry (IHC) in surgical tissues from a total of 42 patients with surgically confirmed PTC, and compared in patients with and without CLNM. Further, to assess PC expression in diagnostic biopsies, a total of 71 thyroid nodule patients with ultrasound-guided FNA wash-out fluid samples and cytological diagnosis were prospectively enrolled in the study. Then, we analyzed the mechanism of PC-mediated PTC progression in vitro. This study showed that PC expression was higher in PTC tissues and thyroid FNA wash-out fluid samples from patients with CLNM than those from patients without CLNM, and that PC-induced PTC metastasis may occur through the TGF-β/Smad-regulated epithelial–mesenchymal transition (EMT) pathway.

Objective: Upper limb (UL) motor function recovery, especially distal function, is one of the main goals of stroke rehabilitation as this function is important to perform activities of daily living (ADL). The efficacy of the motor-imagery brain-computer interface (MI-BCI) has been demonstrated in patients with stroke. Most patients with stroke receive comprehensive rehabilitation, including MI-BCI and routine training. However, most aspects of MI-BCI training for patients with subacute stroke are based on routine training. Risk factors for inadequate distal UL functional recovery in these patients remain unclear; therefore, it is more realistic to explore the prognostic factors of this comprehensive treatment based on clinical practice. The present study aims to investigate the independent risk factors that might lead to inadequate distal UL functional recovery in patients with stroke after comprehensive rehabilitation including MI-BCI (CRIMI-BCI).Methods: This prospective study recruited 82 patients with stroke who underwent CRIMI-BCI. Motor-imagery brain-computer interface training was performed for 60 min per day, 5 days per week for 4 weeks. The primary outcome was improvement of the wrist and hand dimensionality of Fugl-Meyer Assessment (δFMA-WH). According to the improvement score, the patients were classified into the efficient group (EG, δFMA-WH > 2) and the inefficient group (IG, δFMA-WH ≤ 2). Binary logistic regression was used to analyze clinical and demographic data, including aphasia, spasticity of the affected hand [assessed by Modified Ashworth Scale (MAS-H)], initial UL function, age, gender, time since stroke (TSS), lesion hemisphere, and lesion location.Results: Seventy-three patients completed the study. After training, all patients showed significant improvement in FMA-UL (Z = 7.381, p = 0.000**), FMA-SE (Z = 7.336, p = 0.000**), and FMA-WH (Z = 6.568, p = 0.000**). There were 35 patients (47.9%) in the IG group and 38 patients (52.1%) in the EG group. Multivariate analysis revealed that presence of aphasia [odds ratio (OR) 4.617, 95% confidence interval (CI) 1.435–14.860; p < 0.05], initial FMA-UL score ≤ 30 (OR 5.158, 95% CI 1.150–23.132; p < 0.05), and MAS-H ≥ level I+ (OR 3.810, 95% CI 1.231–11.790; p < 0.05) were the risk factors for inadequate distal UL functional recovery in patients with stroke after CRIMI-BCI.Conclusion: We concluded that CRIMI-BCI improved UL function in stroke patients with varying effectiveness. Inferior initial UL function, significant hand spasticity, and presence of aphasia were identified as independent risk factors for inadequate distal UL functional recovery in stroke patients after CRIMI-BCI.

Introduction Sleep apnea/hypopnea syndrome (SAHS) can change brain structure and function. These alterations are related to respiratory event-induced abnormal sleep, however, how brain activity changes during these events is less well understood. Methods To study information content and interaction among various cortical regions, we analyzed the variations of permutation entropy (PeEn) and symbolic transfer entropy (STE) of electroencephalography (EEG) activity during respiratory events. In this study, 57 patients with moderate SAHS were enrolled, including 2804 respiratory events. The events terminated with cortical arousal were independently researched. Results PeEn and STE were lower during apnea/hypopnea, and most of the brain interaction was higher after apnea/hypopnea termination than that before apnea in N2 stage. As indicated by STE, the respiratory events also affected the stability of information transmission mode. In N1, N2, and rapid eye movement (REM) stages, the information flow direction was posterior-to-anterior, but the anterior-to-posterior increased relatively during apnea/hypopnea. The above EEG activity trends maintained in events with cortical arousal. Conclusions These results may be related to the intermittent hypoxia during apnea and the cortical response. Furthermore, increased frontal information outflow, which was related to the compensatory activation of frontal neurons, may associate with cognitive function.

The relationship between preoperative tibiofemoral position and failure of anterior cruciate ligament (ACL) reconstruction has been widely discussed. Most established methods for measuring tibiofemoral position on magnetic resonance imaging (MRI) mainly focus on anterior tibial subluxation (ATS), while a quantitative measuring method for rotational tibial subluxation (RTS) is still undetermined. Moreover, there are still controversies about the related factors for ATS. The aim of this study was to quantitatively describe preoperative ATS and RTS in ACL-injured and ACL-intact knees and identify the related factors for ATS and RTS based on MRI images.Demographic data and preoperative MRIs of 104 ACL-injured patients were retrospectively analyzed. ACL-intact knees were 1:1 matched as control group. ATS was measured using longitudinal tibial axis, and RTS was determined by the difference between lateral and medial ATS. Related factors for ATS and RTS were examined.Increased lateral ATS (P 0.0001), medial ATS (P 0.0001) and RTS (P = 0.0479) were observed in ACL-injured knees compared with the control group. Increased posterior tibial slope (PTS), Beighton Score ≥ 4, presence of meniscal injury and long injury-to-MRI time were identified as being correlated with the increase of ATS. Factors for the increase of RTS were increased lateral PTS, Beighton score ≥ 4, presence of lateral meniscal injury, and left side.In ACL-injured knees, tibia not only subluxated anteriorly in both lateral and medial compartments, but also rotated internally. During preoperative planning, attentions should be paid to the factors that are correlated with altered tibiofemoral position.

Haemophilia care in Taiwan has come a long way over the past 35 years, from the absence of specialised haemophilia treatment centres before 1984 to the establishment of treatment centers in the majority of medical centers, the listing of haemophilia as a catastrophic illness with full treatment reimbursement by the Taiwan National Health Insurance (NHI), and the implementation of full NHI coverage for prophylaxis therapy. This has led to outcome improvements such as reduced bleed-related morbidity and mortality, fewer viral infections, and enhanced overall multi-modality care. Most people with haemophilia (PWH) are now able to live normal, active lives. Early diagnosis has improved through increased awareness, physician education, and prenatal diagnosis; while comprehensive care, including state of the art rehabilitation and orthopaedic management for haemophilic arthropathy, eradication therapy for chronic hepatitis C, and better treatments for human immunodeficiency virus, allows PWH to enjoy a better quality of life and improved survival. Efforts are now being made to raise prophylaxis rates through full NHI reimbursement and the use of extended half-life recombinant factor products. Overall, Taiwan has made great strides in haemophilia care and we would like to share these experiences for the benefit of all healthcare providers involved in haemophilia care.

BackgroundThe role of laparoscopic hepatectomy (LH) in hepatocellular carcinoma (HCC) with cirrhosis remains controversial and needs to be further assessed. The present meta-analysis aimed to compare the surgical and oncological outcomes of LH with those of open hepatectomy (OH) for HCC with cirrhosis.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for studies comparing LH and OH until Mar 2021. Weighted mean differences (WMDs), odds ratios (ORs), and hazard ratios (HRs) were calculated for continuous, dichotomous, and long-term variables, respectively, with 95% confidence intervals (CIs). Subgroup analysis was performed according to different resection types: major resection and minor resection. The meta-analysis was performed using the STATA 12.0.ResultsA total of 16 case-matched studies (784 patients in the LH group and 1,191 patients in the OH group.) were included in this meta-analysis. In terms of primary outcomes, LH was associated with decreased overall complication rate (OR 0.57; 95% CI 0.46 to 0.71; P ConclusionLH is technically feasible and safe for selected HCC patients with cirrhosis. LH can achieve favored short-term and long-term oncological outcomes in minor liver resection. Laparoscopic major hepatectomy (LMH) seems to offer some advantages over the open approach; however concerns about surgical and oncological safety remain. More evidence on LMH is warranted before expanding its indication to patients with cirrhosis.

The expression of Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) has been reported to be dysregulated in non-small cell lung carcinoma, especially in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate the functional and prognostic roles of PELP1 in LUAD in this study. We first immunolocalized PELP1 in 76 cases of LUAD and 17 non-pathological or tumorous lung (NTL) tissue specimens and correlated the findings with the clinicopathological parameters of the patients. We then performed in vitro analysis including MTT, flow cytometry, wound healing, and transwell assays in order to further explore the biological roles of PELP1 in 17-β-estradiol (E2) induced cell proliferation, migration, and invasion of LUAD cells. We subsequently evaluated the prognostic significance of PELP1 in LUAD patients using the online survival analysis tool Kaplan-Meier Plotter. The status of PELP1 immunoreactivity in LUAD was significantly higher than that in the NTL tissues and significantly positively correlated with less differentiated features of carcinoma cells, positive lymph node metastasis, higher clinical stage as well as the status of ERα, ERβ, and PCNA. In vitro study did reveal that E2 promoted cell proliferation and migration and elevated PELP1 protein level in PELP1-high A549 and H1975 cells but not in PELP1-low H-1299 cells. Knock down of PELP1 significantly attenuated E2 induced cell proliferation, colony formation, cell cycle progress as well as migration and invasion of A549 and H1975 cells. Kaplan-Meier Plotter revealed that LUAD cases harboring higher PELP1 expression had significantly shorter overall survival. In summary, PELP1 played a pivotal role in the estrogen-induced aggressive transformation of LUAD and could represent adverse clinical outcome of the LUAD patients.

Background Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Currently, laparoscopic pancreatic resection (LPR) is extensively applied to treat benign and low-grade diseases related to the pancreas. The viability and safety of LPR for PDAC needs to be understood better. Laparoscopic distal pancreatectomy (LDP) and pancreaticoduodenectomy (LPD) are the two main surgical approaches for PDAC. We performed separate propensity score matching (PSM) analyses to assess the surgical and oncological outcomes of LPR for PDAC by comparing LDP with open distal pancreatectomy (ODP) as well as LPD with open pancreaticoduodenectomy (OPD). Methods We assessed the data of patients who underwent distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for PDAC between January 2004 and February 2020 at our hospital. A one-to-one PSM was applied to prevent selection bias by accounting for factors such as age, sex, body mass index, and tumour size. The DP group included 86 LDP patients and 86 ODP patients, whereas the PD group included 101 LPD patients and 101 OPD patients. Baseline characteristics, intraoperative effects, postoperative recovery, and survival outcomes were compared. Results Compared to ODP, LDP was associated with shorter operative time, lesser blood loss, and similar overall morbidity. Of the 101 patients who underwent LPD, 10 patients (9.9%) required conversion to laparotomy. The short-term surgical advantage of LPD is not as apparent as that of LDP due to conversions. Compared with OPD, LPD was associated with longer operative time, lesser blood loss, and similar overall morbidity. For oncological and survival outcomes, there were no significant differences in tumour size, R0 resection rate, and tumour stage in both the DP and PD subgroups. However, laparoscopic procedures appear to have an advantage over open surgery in terms of retrieved lymph nodes (DP subgroup: 14.4 ± 5.2 vs. 11.7 ± 5.1, p = 0.03; PD subgroup 21.9 ± 6.6 vs. 18.9 ± 5.4, p = 0.07). These two groups did not show a significant difference in the pattern of recurrence and overall survival rate. Conclusions Laparoscopic DP and PD are feasible and oncologically safe procedures for PDAC, with similar postoperative outcomes and long-term survival among patients who underwent open surgery.

Objective To observe the effect of moxibustion on the survival status and nutritional metabolic factors of tumor-bearing rats with gastric cancer and explore the inhibitory effect of moxibustion on the tumor-bearing rats. Methods A total of 40 SD rats were randomly divided into a blank group, a sham-operated group, a model group and a moxibustion group, 10 rats in each group. Gastric cancer models were established in the model group and the moxibustion group. The rats of all the groups underwent the same constraining procedure for 20 min every day. Additionally, moxibustion was applied at acupoints for 20 min in the rats of the moxibustion group. There were two groups of acupoints. One group included “Zusānlĭ (足三里ST 36)” “Zhōngwan (中脘CV12) ” and “Guānyuan (关元CV4) ”. The other group included bilateral “Pĭshū(脾俞BL 20) ” and “Weishū(胃俞BL 21) ”. Moxibustion was applied for 20 min every day at the acupoints of the two groups alternatively and lasted for 14 days. The survival status of rats was observed and the score of survival status and body weight of rats were recorded every day. At the end of intervention, the orbital blood was collected and the rats were sacrificed for sample collection. The viscera-free body weight was recorded. Using biochemical analyzer, the blood glucose (GLU), albumin (ALB), total protein (TP) and triglyceride (TG) in serum were detected. Results (1) Regarding the score of the survival status, after modeling, the scores in the model group and the moxibustion group were all higher than those of the sham-operation group (both P Conclusion Moxibustion improves the survival status of tumor-bearing rats with gastric cancer, increases the body weight, the viscera-free body weight and the levels of GLU and ALB in serum and reduces TP of the tumor-bearing rats with gastric cancer and inhibits the growth of gastric cancer.

The current study explores potential characteristic metabolic signatures associated with the high cholesterol (CHO), and the progression of coronary artery stenosis (CAS) in high-CHO patients. A metabolomics strategy based on ultra high-performance liquid chromatography/MS-MS and multivariate statistics has been implemented to identify potential biomarkers in high-CHO patients with different levels of CAS. The current study included 57 individuals, comprising 17 healthy paticipants, and 40 high-CHO patients. The high CHO patients were subgrouped based on the computed tomography angiography results, that is, CHO+ no ART (n = 10), CHO+ ART less than 50% (n = 13), CHO+ ART 50-75% (n = 11), and CHO+ ART more than 75% (n = 6). After metabolomics study, 16 discriminating metabolites in positive ion mode and 17 discriminating metabolites in negative ion mode were regarded as possible biomarker candidates to reflect metabolic traits differences between patients with healthy subjects and CHO. A total of six metabolites were tentatively identified as potential biomarkers for the progression diagnosis of CAS: three lysophosphatidylcholines (Lyso-phosphocholine, lysoPC and Lysopersicon esculentum, lysoPE), proline betaine and tryptophan, and prasterone sulfate. The results demonstrated that tryptophan and proline betaine could differentiate the patients with or without high CHO. Tryptophan, prasterone sulfate, LysoPE (0 : 0/18 : 2) or LysoPE (18 : 2/0 : 0), and LysoPE (0 : 0/18 : 1) or LysoPE (18 : 1/0 : 0) could differentiate the patients with severe stenosis (ART > 70%) from the healthy or mild stenosis ones. Proline betaine and significant decrease of LysoPC (17 : 0) could also be a promising biomarker for the mild stenosis (ART

Background Lymphedema is the most common complication after breast cancer treatment, but management of lymphedema remains a clinical challenge. Several studies have reported the beneficial effect of acupuncture for treating breast cancer-related lymphedema (BCRL). Our objective is to verify the effectiveness of warm acupuncture on BCRL and compare the effectiveness of a local distribution acupoint combination with a local-distal acupoint combination for BCRL. Methods This is a study protocol for a multicenter, three-arm parallel, assessor blinded, randomized controlled trial. A total of 108 participants diagnosed as BCRL will be randomly allocated in equal proportions to a local distribution acupoint (LA) group, a local-distal acupoint (LDA) group, or a waiting-list (WL) group. The LA and LDA groups will receive 20 acupuncture treatment over 8 weeks with local distribution acupoint combination and local-distal acupoint combination, respectively. The WL group will receive acupuncture treatment after the study is concluded. The primary outcome is the mean change in inter-limb circumference difference from baseline to week 8. The secondary outcomes include volume measurement, skin hardness, common terminology criteria for adverse events 4.03 (edema limbs criteria), stages of lymphedema from the International Society of Lymphology, Disabilities of the Arm, Shoulder and Hand questionnaire, and the Medical Outcome Study 36-item Short-form Health Survey. Discussion This study aims to provide data on warm acupuncture as an effective treatment for BCRL and at the same time compare the effectiveness of different acupoint combinations. Trial registration ClinicalTrials.gov: Identifier NCT03373474. Registered on 14th December 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3491-4) contains supplementary material, which is available to authorized users.

Sanguinarine (SAN), a quaternary benzophenanthridine alkaloid extracted from the root of Papaveraceae plants, has shown antitumour effects in multiple cancer cells. However, the therapeutic effects and the underlying mechanisms of SAN in gastric cancer (GC) remain elusive. In this study, the in vitro proliferation inhibition effect of SAN in GC cells was determined using CCK-8 assay, the in vivo antitumor effect of SAN was evaluated in mice with xenotransplanted tumor. The mechanism underlying the antitumor activity of SAN was explored by gene microarray assay and bioinformatics analysis. The levels of differentially expressed miRNAs and target genes were verified by real-time RT-PCR and immunohistochemistry. SAN inhibited the proliferation of BGC-823 cells in a concentration-dependent manner in vitro and in vivo. The miR-96-5p and miR-29c-3p were significantly upregulated in untreated BGC-823 cells and significantly downregulated in SAN treated cells. The mRNA and protein expression of their target gene MAP4K4 were upregulated in SAN treated xenotransplanted tumors, and pMEK4 and pJNK1 proteins in the MAPK/JNK signaling pathway were also upregulated by SAN. These indicate that SAN may inhibit the proliferation of BGC-823 cells through the inhibition of miR-96-5p and miR-29c-3p expression, and subsequent activation of the MAPK/JNK signaling pathway.

To explore the inhibitory effect of moxibustion on tumor growth and metastasis, and also its possible mechanism, in gastric tumor-bearing rats by investigating the expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). Fifty healthy Sprague-Dawley (SD) rats (half male and half female) were routinely housed for 1 week. A total of 20 rats were randomly divided into a blank group and a sham operation group, with 10 rats in each group. The remaining 30 rats were used to make gastric cancer models by implantation of ascites-type Walker-256 cancer cells. After successful modeling, rats were randomly divided into a model group, a moxibustion group and an infrared group, with 10 rats in each group. From the day of modeling, the body weight of each group was weighed every 4 days. Warm moxibustion was alternately performed at two-group acupoints [Zhongwan (CV 12), Guanyuan (CV 4) and bilateral Zusanli (ST 36) in one group, and bilateral Pishu (BL 20) and Weishu (BL 21) in another group] in the moxibustion group. The body surface projection area of the stomach was irradiated with short-wave infrared rays in the infrared group, once a day, 20 min per time for 21 d. At the end of the treatment, the gastric tumor was completely dissected, and the tumor volume and tumor growth inhibition rate were calculated. Then the gastric tumor cell metastasis was recorded. The levels of VEGF and EGF in rat gastric tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA). Compared with the blank group, the body weight of the model group decreased significantly after modeling (P

Human homolog of mouse double minute 2 (HDM2) is an oncogene frequently overexpressed in cancers with poor prognosis, but mechanisms of controlling its abundance remain elusive. In an unbiased biochemical search, we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCF(FBXO22)) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation. In human breast cancer cells, FBXO22 knockdown (KD) increased cell invasiveness, which was driven by elevated levels of HDM2. Moreover, mouse 4T1 breast tumor model studies revealed that FBXO22 KD led to a significant increase of breast tumor cell metastasis to the lung. Finally, low FBXO22 expression is correlated with worse survival and high HDM2 expression in human breast cancer. Altogether, these findings suggest that SCF(FBXO22) targets HDM2 for degradation and possesses inhibitory effects against breast cancer tumor cell invasion and metastasis.

Purpose Fractures of the distal femur remain challenging to treat, and numerous fixation methods are designed to promote stability and fracture healing. Locking plate constructs have recently become the mainstream fixation method, but debate exists on whether to use locking plates alone or to augment them with interfragmentary screws. This article compares outcomes of distal femur fractures treated with a single locking plate alone versus those treated with a locking plate and interfragmentary screws. Methods We retrospectively reviewed 57 patients treated for distal femur fractures from 2010 to 2013. Patients were divided into two groups: Those treated with a locking plate alone utilizing the minimally invasive plate osteosynthesis (MIPO) technique and those treated with combination of a locking plate and interfragmentary screws using an open technique. Postoperative outcomes were obtained via a manual chart review. Fracture healing and callus indices were evaluated from radiographs. Results 9 patients required revision surgery in the locking plate alone group (6 for persistent nonunion and 3 for varus deformity). Only two patients in the combination group required revisions (both for nonunion). Average time to full weight bearing was 19.54 weeks in the locking plate group versus 14.57 weeks in the combination group (p = 0.004). At the time of full weight bearing, frontal (1.15 versus 1.11, p = 0.004) and sagittal (1.22 versus 1.15, P = 0.008) callus indices were both significantly greater in the locking plate group. Conclusions In this study, the combination of a locking plate and interfragmentary screws achieved suitable stability and a faster time to full weight bearing than using a locking plate alone. Surgeons should consider combining a locking plate with interfragmentary screws as an effective method for fixation of distal femur fractures, particularly in cases when plate fixation alone fails to provide adequate fracture stability.

Background The prevalence of obesity in patients with hemophilia (PWH) varies among different ethnicities, and its influence on joint bleeding and hemophilic arthropathy has not been studied in Taiwan population. We explored the prevalence and clinical correlates of obesity and the impact of body mass index (BMI) on annual joint bleeding rate (AJBR) and hemophilic arthropathy in PWH in Taiwan. Methods We retrospectively collected clinical information on 140 severe/40 moderate PWH from 2006 to 2014. The patients' median age was 31.5 years, ranged from 6 to 73 years. Their BMI, 6 index joints score by Pettersson scoring, AJBR, and other clinical data were analyzed. Results The prevalence of overweight and obesity by age group was 7.1% in PWH aged ≤10 years, and rapidly increased to 34.5% in PWH aged 11 to 18 years, 46.7% in PWH aged 18 to 29 years, 61.8% in PWH aged 30 to 39 years, 60.6% in PWH aged 40 to 49 years, and 48% in PWH aged ≥50 years, respectively. Two peak rates were 72.7% in PWH aged 35 to 44 years and 66.7% in PWH aged >65 years. Age, HCV infection, knee score, elbow score, and total 6 index joints scores were found to correlate positively with BMI. However, subtype and severity of hemophilia, ankle scores, HBV and HIV infection did not correlate with BMI. Finally, BMI was found to correlate positively with AJBR in both adult and pediatric PWH. Conclusion The prevalence of overweight and obesity in adolescent and adult PWH was higher than those in the general male population in Taiwan, which rapidly increased with age to peak in PWH aged 35 to 44 years and >65 years. High index joint score, with the exception of ankle scores, positively correlated with high BMI. Further, BMI and obesity also had positive correlation with AJBR in PWH. To our knowledge, this is the first study examining these associations in PWH in Taiwan.

The application of laparoscopic hepatectomy is gaining momentum. However, the safety and efficacy of laparoscopic right hepatectomy (LRH) on hepatocellular carcinoma (HCC) are yet to be adequately evaluated. We aimed to assess the surgical and oncological outcomes of LRH for HCC by comparing it with open right hepatectomy (ORH).Data of patients who underwent hepatectomy for HCC from May 2007 to January 2018 in our hospital were obtained. Baseline characteristics, postoperative recovery, and survival outcomes were compared. One-to-one propensity score matching (PSM) was used to minimize selection biases by balancing factors, including age, sex, preoperative therapy, tumor size, and pattern.The original cohort included 109 patients (LRH, 41 patients; ORH, 68 patients). Of the 41 patients who underwent LRH, 8 patients (19.5%) required conversion to laparotomy. The overall morbidity was 19.5%, and no mortality in LRH was noted. After PSM, LRH was associated with a tendency of prolonged operative time (255.5 ± 93.4 minutes versus 225.9 ± 39.8 minutes, P = .08) and less intraoperative blood loss [300 (100-1200) versus 500 (200-2000) mL, P .01]. LRH showed up a trend of less overall morbidity without statistical significance (18.4% versus 26.3%, P = .41). Moreover, the 3-year overall and disease-free survival did not differ significantly between the groups during a median follow-up of 19 (3-58) months for the LRH group and 23 (3-97) months for the ORH group.LRH can be performed as safe and effective as ORH for HCC in regard to both surgical and oncological outcomes. LRH holds the benefit in less intraoperative blood loss and appears to achieve less postoperative morbidity, which could serve as a promising alternative to ORH in selected individuals.