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We aimed to identify which enteral feeding method was most beneficial for patients and compare clinical outcomes, quality of life, and complication rates by assessing patients who underwent prophylactic percutaneous endoscopic gastrostomy (pPEG) tube, reactive percutaneous endoscopic gastrostomy (rPEG) tube or reactive nasogastric tube (rNGT) insertion.Patients with head and neck cancers (HNCs) were enrolled between April 1, 2013 and April 17, 2019 (n = 335; 296 males, 39 females). Data concerning patient characteristics and treatment modalities were extracted from the medical records. Comparisons between enteral feeding methods were made by univariate and multivariate analysis. Overall survival (OS) outcomes were analyzed by the log rank test using the Kaplan-Meier method.A total of 335 patients were included. The median follow-up time was 29.5 months. There were forty-six patients in the pPEG tube group, 23 patients in the rPEG tube group, and 266 patients in the rNGT group. pPEG, increased body-mass index (BMI), and N0-1 category were significantly associated with less weight loss in the multivariate analysis (all P lt; 0.05). pPEG decreased the rate of radiotherapy delay compared with that of reactive interventions (23.1% vs. 47.1%, P = 0.007). In terms of quality of life, global health status, role functioning, emotional functioning, cognitive functioning, pain, and dyspnea were significantly improved in the pPEG tube group (all P lt; 0.05). BMI and weight loss were independent prognostic factors for clinical survival outcomes (all P lt; 0.05).pPEG could improve nutrition outcomes, reduce treatment delay, and maintain quality of life.

Background Uncaria tomentosa, which has similar chemical constituents with Uncaria rhynchophylla, has been reported to alleviate cognitive impairments in Alzheimer’s disease (AD) animal models. This study aimed to compare the chemical constituents and anti-AD effect of the ethanol extracts of U. tomentosa (UTE) and U. rhynchophylla (URE). Methods The high-performance liquid chromatography (HPLC) was used to compare the chemical constituents of UTE and URE. Streptozotocin (STZ) was intracerebroventricularly (ICV) injected into adult male Sprague–Dawley (SD) rats to establish AD model. UTE (400 mg/kg) or URE (400 mg/kg) was administrated intragastrically once daily to the rats for 6 consecutive weeks. Morris water maze (MWM) test was conducted to assess the neurological functions in the STZ-induced AD rats. The brain tissues of the rats were harvested for further biochemical assay. Results The MWM test results showed both UTE and URE could significantly improve the learning and memory impairments induced by STZ in rats. Both UTE and URE could significantly inhibit the hyperphosphorylation of tau protein, reduce the elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), enhance activities of antioxidant enzymes (SOD, CAT and GPx) and increase the protein expression of HO-1. In addition, UTE could decrease the malondialdehyde (MDA) level. Furthermore, both UTE and URE significantly enhanced Akt activation, down regulated the activation of glycogen synthase kinase 3β (GSK-3β), and induced the nuclear translocation of Nrf2 in the STZ-induced AD rats. Conclusions UTE and URE contained similar chemical constituents. We found for the first time that both of them could ameliorate cognitive deficits in the STZ-induced AD rats. The underlying molecular mechanism involve suppression of tau hyperphosphorylation, anti-oxidant and anti-neuroinflammation via modulating Akt (Ser473)/GSK3β (Ser9)-mediated Nrf2 activation. These findings amply implicate that both of UTE and URE are worthy of being developed clinically into pharmaceutical treatment for AD.

Objectives The study aims to analyze the clinical characteristics of head and neck mucosal melanoma (MMHN) and the effects of multiple treatment modalities on distant metastasis, recurrence and survival rates to provide a reference for the individualized treatment of MMHN. Methods We retrospectively reviewed 262 patients with stage III–IVb MMHN treated from March 1986 to November 2018 at our cancer center. Results The median follow-up time was 34.0 months (range 1–262 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) probabilities were 37.7%, 30.2%, and 20.3%, respectively. The 5-year OS rates for patients with stage III, stage IVA, and stage IVB MMHN were 67.0%, 24.1% and 8.3%, respectively (P P P P Conclusions The main reason for treatment failure in MMHN is distant metastasis. Immunologic/targeted therapy and surgery are recommended to improve the survival of MMHN. The American Joint Committee on Cancer (AJCC) 8th edition staging system for MMHN does stage this disease effectively.

Objectives We aimed to understand the clinical characteristics and better predict the prognosis of patients with mucosal melanoma of the head and neck (MMHN) using a nomogram. Methods Three hundred patients with nometastatic MMHN were included. Multivariable Cox regression was performed to analyze independent prognostic factors for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS), and these factors were used to develop a nomogram. Concordance indexes (C-indexes), calibration plots, and receiver operating characteristic (ROC) analysis were performed to test the predictive performance of the nomogram in both the primary (n = 300) and validation cohorts (n = 182). Results The primary tumor site, T stage and N stage were independent risk factors for survival and were included in the nomogram to predict the 3- and 5-year OS, DFS, DMFS, and LRRFS in the primary cohort. The C-indexes (both > 0.700), well-fit calibration plots, and area under the ROC curve (both > 0.700) indicated the high diagnostic accuracy of the nomogram, in both the primary and validation cohorts. The patients were divided into three groups (high-risk, intermediate-risk, and low-risk groups) according to their nomogram scores. The survival curves of OS, DFS, DMFS, and LRRFS were well separated by the risk groups in both cohorts (all P Conclusions The nomogram can stratify MMHN patients into clinically meaningful taxonomies to provide individualized treatment.

Aberrant factors associated with fibrinolysis and thrombosis are found in many cancer patients, which can promote metastasis and are associated with poor prognosis. The relationship between tumor-associated fibrinolysis and thrombosis is poorly understood in pancreatic cancer. This review provides a brief highlight of existing studies that the fibrinolysis and coagulation systems were activated in pancreatic cancer patients, along with aberrant high concentrations of tissue plasminogen activator (t-PA), urine plasminogen activator (u-PA), D-dimer, fibrinogen, or platelets. These factors cooperate with each other, propelling tumor cell shedding, localization, adhesion to distant metastasis. The relationship between thrombosis or fibrinolysis and cancer immune escape is also investigated. In addition, the potential prevention and therapy strategies of pancreatic cancer targeting factors in fibrinolysis and coagulation systems are also been discussed, in which we highlight two effective agents aspirin and low-molecular weight heparin (LMWH). Summarily, this review provides new directions for the research and treatment of pancreatic cancer.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Patchouli alcohol (PA), a major active ingredient isolated from Pogostemonis Herba, exhibits extensive bioactivity in the central nervous system (CNS) and exerts neuroprotective effects.This study aimed to investigate the anti-AD effects of PA in an animal model of AD and to elucidate the underlying molecular mechanisms.The gas chromatography (GC) was used to determine the ability of PA to pass the blood-brain barrier (BBB) in rats after oral administration. The sporadic AD rat model was established by intracerebroventricularly (ICV) injection with streptozotocin (STZ). PA (25 and 50 mg/kg) was given to rat orally once daily for 42 consecutive days. Morris water maze (MWM) test was performed to determine the learning and memory functions of the STZ-induced AD rats. EX527, a silent information regulator 1 (SIRT1) selective inhibitor, was used to investigate the involvement of SIRT1 in the anti-AD effects of PA in rats.PA could penetrate the BBB. MWM test results showed that PA could significantly ameliorate the learning and memory deficits induced by STZ in rats. Meanwhile, PA enhanced the expression of SIRT1, and markedly alleviated the tau pathology by inhibiting the hyperacetylation (at the site of Lys174) and hyperphosphorylation (at the sites of Thr181, Thr205, Ser396 and Ser404) of tau protein. PA also efficiently suppressed the activation of microglia and astrocytes, and the beta-amyloid (Aβ) expression and the deacetylation of nuclear factor-kappa B (NF-κB) at Lys 310 (K310) in the STZ-treated AD rats. EX527, a SIRT1 selective inhibitor, could partially abolish the cognitive deficits improving effect of PA and inhibit the down-regulation of acetylated tau and acetylated NF-κB p65, suggesting that PA exhibited neuroprotective effects against AD via upregulating SIRT1.This study reported for the first time that PA could penetrate the BBB to exert its protective effects on the brain after a single-dose oral administration. The current experimental findings also amply demonstrated that PA could improve the cognitive and memory impairments in the STZ-induced AD rat model. The underlying mechanisms involve the alleviations of neuroinflammation, tau pathology and Aβ deposition via modulating of SIRT1 and NF-κB pathways. All these findings strongly suggest that PA is a promising naturally occurring compound worthy of further development into an anti-AD pharmaceutical.

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder characterized by progressive loss of memory and cognitive functions. There are two pathological hallmarks, including accumulation of amyloid plaques composed of β-amyloid peptide (Aβ) and deposits of neurofibrillatory tangles (NFT). Cyclin-dependent kinase 5 (CDK5), a serine/threonine kinase, plays an important role in synaptic plasticity and cognitive behavior. Sulforaphene (SF) has been demonstrated to exert anti-AD activity in AD rat model. In this study, we aimed to evaluate the cognitive deficits improving effects of SF on in TgCRND8 mice and to elucidate the underlying molecular mechanisms.TgCRND8 mice were intragastrically treated with SF (25 and 50 mg/kg) for 4 months from 3-month-old. The cognitive functions were assessed using Morris Water Maze Test. Cultured primary mouse neurons were pre-treated with SF, followed by co-treatment with Aβ1-42 oligomers. CDK5 inhibitor (roscovitine) was used to determine the involvement of CDK5/p25 pathway in the anti-AD effects of SF in primary neurons.Our results showed that SF treatment significantly ameliorated the cognitive deficits in TgCRND8 mice and protected primary mouse neurons against Aβ1-42 induced neurotoxicity. SF could modulate the expression of Aβ production related markers, and suppress the phosphorylation of tau protein at specific sites in the TgCRND8 mice. In addition, SF enhanced the expressions of synaptic plasticity related markers and CDK5. SF also markedly suppressed the CDK5/p25 activity.SF is a potent CDK5 inhibitor and a potential therapeutic agent for treatment and prevention of AD. Moreover, SF inhibited the overexpression of CDK5 in primary neurons of mouse.

Background: Occupational irritant contact dermatitis (OICD) commonly manifests skin barrier function disrupted. The composition of the skin surface lipids (SSLs) determined the skin barrier function. This study aims to evaluated the repair effect of moisturizer on the skin barrier function of OICD patients and lipidomic tools were used to explore potential repair mechanisms.Methods: A before-after in the same patient study of real-world during December 2019 in Zhengzhou, China. 15 shampoo workers insisted on using moisturizer (2g each time, about 10 times a day) in their back of hands during work breaks. SSLs as main outcome, skin moisture content and trans epidermal water loss (TEWL) as secondary outcome were used to evaluate alteration of skin barrier function at different research stages.Results: After using moisturizer for 2 weeks, skin moisture increased significantly (pConclusion: Moisturizer could be used as effective interventions to increase SSLs and repair skin barrier function to a certain extent in OICD patients.Trial registration: This study was reviewed and approved by the Zhengzhou University's Life Science Ethics Review Committee and Registered in the Chinese Clinical Trial Registry (ID: ChiCTR2000034103). Informed consent to participates were obtained before enrollment.

Drought is one of the most important abiotic stressors that affect crop yield. Therefore, the aim of the present study was to investigate correlations between germination-stage drought tolerance and the microscopic testa (i.e., seed coat) characteristics (color and papilla morphology) and imbibition abilities of 35 rapeseed (Brassica napus L.) accessions. After 2 h imbibition, seed water uptake (fresh weight increase) was significantly positively correlated with testa hue (HHSB), brightness (BHSB,), blue (BRGB), and lightness (L*), with correlation coefficients of 0.38, 0.34, 0.53, and 0.36, respectively, and significantly negatively correlated with saturation (SHSB), greenness-redness (a*), blueness-yellowness (b*), magenta (M), and yellow components (Y), with correlation coefficients of −0.53, −0.40, −0.53, −0.39, and −0.55, respectively. Furthermore, 5-h seed water uptake was significantly positively correlated with number of papillae (No.P), mean papillae area (APA), the papillae area ratio (PAR), gray value of red channel of papillae, with correlation coefficients of 33, 0.36, 0.43, and 0.43, respectively. Under drought conditions, genotypes with more rapid water absorption exhibited higher germination rates and stronger drought tolerance, and the germination rate and drought tolerance of black-seeded accessions were highest, followed by red-seeded accessions and then yellow-seeded accessions, which exhibited the lowest germination rate and drought tolerance. Germination rate was significantly negatively correlated with BRGB, HHSB, L*, Dg, and Db and significantly positively correlated with SHSB and Y, regardless of drought conditions. At the germination stage, DbTP was negatively correlated with drought tolerance.

Three new silver–chalcogenide clusters protected by naphthyl ligands are described in this work, namely [Ag14(SCH2C10H7)6(CF3COO)8(DMAc)6] (1), [Ag30(SCH2C10H7)18(CrO4)2(DMAc)2 (CF3COO)8] (DMAc = dimethylacetamide) (2) and {Ag12(SCH2C10H7)6(CF3COO)4(CH3CN)6(Cr2O7)}n (3). Their crystal structures were studied by X-ray crystallography, and they show hollow-core–shell (1), template-core–shell (2) and 1D infinite (3) structures, respectively. The luminescence properties of cluster 1 were investigated, which showed interesting thermochromic variation from red to bright yellow. Moreover, the chromate ions were proven to act as templates in forming the silver clusters through a series of experiments to prepare compounds 2 and 3, which could be considered as derivatives of cluster 1.

Idiopathic pulmonary fibrosis (IPF) is a heterogeneous and progressive fibrosing interstitial lung disease with a poor prognosis. However, there are currently no effective biomarker that can reliably predict the prognosis for IPF in clinic. The serum level of soluble suppression of tumorigenicity-2 (sST2), which is involved in the immune response, has proven to be a prognostic predictor for various diseases. Previous studies have confirmed that the immune dysfunction plays an important role in the pathogenesis of IPF and the serum sST2 concentrations in patients with IPF are elevated. However, the relationship between sST2 and the prognosis of IPF remains unknown.A total of 83 patients with IPF and 20 healthy controls from 2016 to 2021 were enrolled and demographic variables, indices of lung function testing as well as the biomarkers including the sST2 were obtained at baseline. During follow-up, the primary endpoint was defined as all-cause death and clinical deterioration. Cox hazard models and Kaplan-Meier method were used to assess the prognostic value of various indices including sST2.Mean duration of follow-up was 29 months, during which 49 patients had an event, and of them, 35 patients died. The sST2 level was higher in the IPF patients compared with the healthy controls. Although the sST2 level did not directly predict all-cause death in the present study, it was proved to be an independent predictor of event-free survival. Multivariate forward stepwise model which was adjusted by age, sex, and body surface area (BSA) showed that the overexpression of sST2 increased the hazard ratio [1.005, 95% confidence interval (CI): 1.001-1.010]. A higher sST2 serum level heralded more deterioration and the poor outcomes. Moreover, the effect of sST2 on the prognosis of IPF may not necessarily involve the development of IPF-related pulmonary hypertension (PH).In our study, the sST2 serum level was significantly elevated and a higher serum level of sST2 predicted more deterioration and poor outcomes in patients with IPF. Thus, sST2 can serve as a valuable prognostic biomarker for the outcome of IPF. However, further multicenter clinical trials of larger sample size are needed in the future.

Background With the life expectance prolonging, more cancer patients occurred spinal metastases. To evaluate the impact of histologies on outcomes of spinal metastases treated with stereotactic body radiotherapy (SBRT) and identify the correlated prognostic factors. Methods The authors retrospectively reviewed the records of all patients who underwent SBRT with no prior radiation for spinal metastases between October 2015 and October 2020 at Sun Yat-sen University Cancer Center. Propensity score matching (PSM) was applied to balance the distribution of related baseline characteristics. The endpoints included overall survival (OS), local control (LC), pain relief, and time to pain relief. Results A total of 202 consecutive patients with 345 spinal metastases were treated with a median follow-up time of 16.02 months (range, 0.73–57.90 months). The 1- and 2-year OS rates were 57% and 50%, respectively. The median survival was 35.63 months. A higher Karnofsky Performance Scale (KPS) score at consult predicted for better OS (P = 0.020). The presence of pain at enrollment assessed by the Brief Pain Inventory (BPI) predicted for worse OS (P = 0.038). The 1-year LC rate was 92.0%. The pain relief rate was 76.30% (103/135 patients). Younger age was identified to be prognostic for better pain relief (P = 0.037). In the univariate and multivariate analysis, no variable was independently associated with time to pain relief. As for toxicity, no Grade ≥ 3 toxicity was observed. Conclusions SBRT is feasible and appears to be an effective treatment paradigm for patients with spinal metastases, with limited accepted toxicities.

PurposeWe aimed to develop a prognostic immunohistochemistry (IHC) signature for patients with head and neck mucosal melanoma (MMHN).MethodsIn total, 190 patients with nonmetastatic MMHN with complete clinical and pathological data before treatment were included in our retrospective study.ResultsWe extracted five IHC markers associated with overall survival (OS) and then constructed a signature in the training set (n=116) with the least absolute shrinkage and selection operator (LASSO) regression model. The validation set (n=74) was further built to confirm the prognostic significance of this classifier. We then divided patients into high- and low-risk groups according to the IHC score. In the training set, the 5-year OS rate was 22.0% (95% confidence interval [CI]: 11.2%- 43.2%) for the high-risk group and 54.1% (95% CI: 41.8%-69.9%) for the low-risk group (PConclusionsA nomogram was generated and confirmed to be of clinical value. Our IHC classifier integrating five IHC markers could help clinicians make decisions and determine optimal treatments for patients with MMHN.

Objectives: The rarity of mucosal melanoma of the head and neck (MMHN) and the lack of prospective clinical trials has resulted in the limited knowledge of its clinical features and prognosis. We aimed to understand the clinical characteristics and developed a nomogram to better predict the prognosis of patients with MMHN.Methods: Based on a total of 300 patients with nonmetastatic MMHN, multivariable Cox regression was performed to analyze independent prognostic factors. The overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) of MMHN patients could be monitored using the nomogram. To facilitate clinical application, an online dynamic nomogram was established.Results: Multivariate analysis identified primary tumor site, T stage and N stage as independent risk factors for survival. This factor-based nomogram had prognostic value for OS, DFS, DMFS, and LRRFS. Receiver operating characteristic analysis indicated the high diagnostic accuracy of the nomogram (AUC > 0.7). Kaplan–Meier survival curves indicated that the risk score of the nomogram effectively stratified MMHN patients with poor survival into a high-risk group (all PConclusions: The nomogram is conducive to stratifying MMHN patients into clinically meaningful taxonomies and subsequently providing individualized treatment.

Objective: The objective of this study was to investigate whether 70% aqueous ethanol extract of San-Jia-Fu-Mai decoction extract (SJFMDE) could protect against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress in PC12 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor function deficits in mice. Materials and Methods: The cell viability, the levels of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) in the MPP+-treated PC12 cells were measured. Motor function deficits and dopamine (DA) level in the brain striatum and tyrosine hydroxylase (TH)-positive cells in substantia nigra pars compacta (SNc) of the MPTP-treated mice were determined. Results: The results showed that SJFMDE could reduce cell death and the levels of ROS and MDA while increase the level of GSH in the MPP+-treated PC12 cells. In addition, in vivo studies showed that oral administration of SJFMDE (3, 6, and 12 g/kg) significantly improved the motor function deficits induced by MPTP and enhanced the DA level in the striatum and TH-positive neuronal cells in SNc of the MPTP-treated mice. Conclusions: Our results revealed that SJFMDE possessed neuroprotective effects against neurotoxicity induced by MPP + and motor function deficits induced by MPTP via suppressing oxidative stress and increasing the levels of DA and TH, indicating that SJFMDE might be a promising Chinese medicine formula for the treatment of Parkinson's disease.

Drought is one of the most important abiotic stressors that affect crop yield. Therefore, the aim of the present study was to investigate correlations between germination-stage drought tolerance and the microscopic testa (i.e., seed coat) characteristics (color and papilla morphology) and imbibition abilities of 35 rapeseed (Brassica napus L.) accessions. After 2 h imbibition, seed water uptake (fresh weight increase) was significantly positively correlated with testa hue (HHSB), brightness (BHSB,), blue (BRGB), and lightness (L*), with correlation coefficients of 0.38, 0.34, 0.53, and 0.36, respectively, and significantly negatively correlated with saturation (SHSB), greenness-redness (a*), blueness-yellowness (b*), magenta (M), and yellow components (Y), with correlation coefficients of ���0.53, ���0.40, ���0.53, ���0.39, and ���0.55, respectively. Furthermore, 5-h seed water uptake was significantly positively correlated with number of papillae (No.P), mean papillae area (APA), the papillae area ratio (PAR), gray value of red channel of papillae, with correlation coefficients of 33, 0.36, 0.43, and 0.43, respectively. Under drought conditions, genotypes with more rapid water absorption exhibited higher germination rates and stronger drought tolerance, and the germination rate and drought tolerance of black-seeded accessions were highest, followed by red-seeded accessions and then yellow-seeded accessions, which exhibited the lowest germination rate and drought tolerance. Germination rate was significantly negatively correlated with BRGB, HHSB, L*, Dg, and Db and significantly positively correlated with SHSB and Y, regardless of drought conditions. At the germination stage, DbTP was negatively correlated with drought tolerance.

Graphical abstract, Highlights • In the same content, Nano-HO could effectively enhance the bioactivity of HO remarkably and prolonged its circulation time in rats. • Nano-HO improved cognitive deficits in TgCRND8 mice. • Nano-HO suppressed neuroinflammatory response (TNF-α, IL-Iβ, IL-6) inhibited the activation of microglia, astrocyte and A-β plaque burdens in TgCRND8 mice. • Nano-HO ameliorated AD through regulating APP processing, preventing tau hyperphosphorylation and modulating JNK/CDK5/GSK-3β pathway. • Nano-HO regulated the composition and structure of gut microbiota to protect the gut microflora and its stability., Introduction Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer’s disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy. Objectives A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size and excellent stability was developed in this study to improve the solubility and bioavailability of HO. The anti-AD effects of Nano-HO was determined. Methods Male TgCRND8 mice were daily orally administered Nano-HO or HO at the same dosage (20 mg/kg) for 17 consecutive weeks, followed by assessment of the spatial learning and memory functions using the Morris Water Maze test (MWMT). Results Our pharmacokinetic study indicated that the oral bioavailability was greatly improved by Nano-HO. In addition, Nano-HO significantly improved cognitive deficits and inhibited neuroinflammation via suppressing the levels of TNF-α, IL-6 and IL-1β in the brain, preventing the activation of microglia (IBA-1) and astrocyte (GFAP), and reducing β-amyloid (Aβ) deposition in the cortex and hippocampus of TgCRND8 mice. Moreover, Nano-HO was more effective than HO in modulating amyloid precursor protein (APP) processing via suppressing β-secretase, as well as enhancing Aβ-degrading enzymes like neprilysin (NEP). Furthermore, Nano-HO more markedly inhibited tau hyperphosphorylation via decreasing the ratio of p-Tau (Thr 205)/tau and regulating tau-related apoptosis proteins (caspase-3 and Bcl-2). In addition, Nano-HO more markedly attenuated the ratios of p-JNK/JNK and p-35/CDK5, while enhancing the ratio of p-GSK-3β (Ser9)/GSK-3β. Finally, Nano-HO prevented the gut microflora dysbiosis in TgCRND8 mice in a more potent manner than free HO. Conclusion Nano-HO was more potent than free HO in improving cognitive impairments in TgCRND8 mice via inhibiting Aβ deposition, tau hyperphosphorylation and neuroinflammation through suppressing the activation of JNK/CDK5/GSK-3β signaling pathway. Nano-HO also more potently modulated the gut microbiota community to protect its stability than free HO. These results suggest that Nano-HO has good potential for further development into therapeutic agent for AD treatment.

Lei Gu,1,* Siyuan Wen,1,* Chunjie Xu,1 Jiong Zhu,2 Peilin Liu,3 Qing Xu1 1Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Radiology, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing XuDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaEmail renjixuqing@163.comBackground: This study was to evaluate CT vein image segmentation and three-dimensional imaging in the anatomical structure of gastrocolic venous trunk before operation for colon cancer.Methods: CT scanning images by Philips Brilliance CT 256CT scanner. Vein position was segmented and calculated by grey value through algorithm flow. Intensity measurement of selected image area by a calculate through noise cancellation and missing pixel filling, based on numerical morphology.Results: The direction of the right colonic vein could be clearly displayed in all 96 patients by morphological filtering technique. Among these patients, there were 78 patients with gastrocolic vein trunk, with an occurrence rate of 81.25%. According to the classification of GVT, there were 36 cases of type A (46.2%), 22 cases of type B (28.2%), 12 cases of type C (15.4%) and 6 cases of type D (7.7%).Conclusion: CT vein image segmentation and three-dimensional imaging can effectively evaluate the anatomical variation of gastrocolic vein trunk before operation, which is helpful for operators to correctly understand its anatomical structure and choose a reasonable anatomical approach.Keywords: colon cancer, computed tomography angiography, three-dimensional reconstruction, gastrocolic vein trunk, morphological filtering technique

Objective To investigate the relationship between CT radiomic features, pathological classification of pulmonary nodules, and evaluate the prediction effect of different stratified progressive radiomic models on the pathological classification of pulmonary nodules. Methods Altogether, 189 patients pathologically confirmed with pulmonary nodules from July 2017 to August 2019 who had complete data were enrolled, including 71 patients with benign nodules, 51 with malignant non-invasive nodules, and 67 with invasive nodules. Three CT radiomic models were established respectively. Model 1 classified benign and malignant nodules (including malignant non-invasive and invasive nodules). Model 2 classified malignant non-invasive and invasive nodules. Model 3 classified benign, malignant non-invasive, and invasive nodules. High-throughput feature collection was carried out for all delineated regions of interest (ROIs), and the best models were established by screening features and classifiers using intelligent methods. ROC curves and areas under the curve (AUCs) were used to evaluate the prediction efficacy of the models by calculating the sensitivity, specificity, accuracies, positive predictive values, and negative predictive values. Results Through Models 1, 2, and 3, we screened out 20, 2, and 20 radiomic features, respectively, and plotted the ROC curves. In the test group, the AUC values were 0.85, 0.89, and 0.84, respectively; the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.66 %, 70.42 %, 84.59 %, and 81.74 % and 67.57％ for Model 1, 88.06 %, 74.51 %, 82.2 %, 81.94 %, and 82.61 % for Model 2, and 71.34 %, 85.05 %, 70.37 %, 83.2 %, and 76.3 % for Model 3. Conclusion The radiomic feature models based on CT images could well reflect the differences between benign nodules, malignant non-invasive nodules, and invasive nodules, and assist in their classification.

Background Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer’s disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy. A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size and excellent stability was developed in this study to improve the solubility and bioavailability of HO. Methods Male TgCRND8 mice were administered with Nano-HO or HO at the same dosage (20 mg/kg) by oral gavage daily for 17 consecutive weeks, followed by assessment of the spatial learning and memory functions with the Morris Water Maze test (MWMT). Results Nano-HO and HO could significantly improve cognitive deficits and inhibit neuroinflammation via suppressing the levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and IL-1β in the brain, preventing the activation of microglia (IBA-1) and astrocyte (GFAP), and reducing β-amyloid (Aβ) deposition in the cortex and hippocampus of TgCRND8 mice. In addition, Nano-HO and HO could modulate amyloid precursor protein (APP) processing and phosphorylation via suppressing β-secretase including β-site APP cleaving enzyme-1 (BACE-1) and phosphorylated APP (Thr 668), inhibiting γ-secretase including presenilin-1 (PS-1) and anterior pharynx-defective-1 (APH-1), as well as enhancing Aβ-degrading enzymes such as insulin degrading enzyme (IDE) and neprilysin (NEP). Moreover, Nano-HO remarkably inhibited tau hyperphosphorylation via decreasing the levels of p-tau (Thr 205) and p-tau (Ser 404), as well as regulating tau-related apoptosis proteins including caspase-3 and Bcl-2. Furthermore, Nano-HO and HO markedly attenuated the ratios of p-JNK/JNK and p-35/CDK5, while enhancing the ratio of p-GSK-3β (Ser9)/GSK-3β. On the other hand, Nano-HO and HO prevented the alterations on the composition of gut microbiota in TgCRND8 mice. Conclusions Nano-HO was more effective than regular HO in improving cognitive impairments in TgCRND8 mice via inhibiting Aβ deposition, tau hyperphosphorylation and neuroinflammation through suppressing the activation of JNK/CDK5/GSK-3β signaling pathway. Nano-HO was also more potently modulate the gut microbiota community to protect its stability as compared with that of regular HO. Our results amply indicated that HO with nano-sized drug delivery system has good potential for further development into therapeutic agent for AD treatment.

Alzheimer's disease (AD) is the most common form of dementia characterized by progressive loss of cognitive functions due to neuronal death mainly in the hippocampal and cortical brain. Sulforaphene (SF) is one of the main isothiocyanates isolated from a Chinese herb Raphani Semen. In this study, we aimed to investigate the neuroprotective effects of SF using in vitro and in vivo models of AD. Streptozotocin (STZ) was intracranially injected into the rats; then, SF (25 and 50 mg/kg) was given orally once a day for 6 consecutive weeks. After drug treatment, the cognitive functions were assessed using the Morris Water Maze Test (MWMT). After the MWMT, the rats were euthanized and brain tissues were collected. In the in vitro test, BV-2 microglia were pretreated with SF (1 and 2 μM) for 1 h and then stimulated with lipopolysaccharide (LPS) for another 23 h. Both molecular and histological methods were used to unravel the action mechanisms and elucidate the signaling pathway. The MWMT results showed that SF treatment significantly improved the STZ-induced cognitive deficits in rats. SF treatment markedly suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) but increased the release of IL-10 in the STZ-treated rats. In addition, SF significantly inhibited the phosphorylation of tau protein at Thr205, Ser396, and Ser404 sites, while enhancing the ratios of p-Akt (Ser473)/Akt and p-GSK-3β (Ser9)/GSK-3β in the hippocampus of the STZ-treated rats. On the other hand, SF (1 and 2 μM) treatment also markedly attenuated the cytotoxicity induced by LPS in BV-2 cells. In addition, SF treatment obviously suppressed the releases of nitric oxide (NO), TNF-α, and IL-6 in the LPS-stimulated BV-2 cells. Moreover, SF treatment significantly mitigated the nuclear translocation of p-NF-κB p65 and the ratio of p-GSK-3β (Ser9)/GSK-3β in LPS-stimulated BV-2 cells. Taken together, SF possessed neuroprotective effects against the STZ-induced cognitive deficits in rats and LPS-induced neuroinflammation in BV-2 cells via modulation of the PI3K/Akt/GSK-3β pathway and inhibition of the NF-κB activation, suggesting that SF is a promising neuroprotective agent worthy of further development into AD treatment.

The aim of the present study was to evaluate the performance of the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA using one dried blood spot (DBS) as an alternative sample to plasma.A total of 571 paired DBS/plasma samples were collected from men who have sex with men (MSM) and injection drug users (IDUs), and serological and molecular assays were performed. Using plasma results as the reference standard, the performance of DBS tests for HIV-1 RNA, HIV-1 DNA, and HCV RNA was evaluated. Pearson's correlation coefficients and Bland-Altman analysis were performed to assess the correlation and concordance between DBS and plasma.Among paired plasma/DBS samples with detectable HIV-1 RNA and HCV RNA, five samples (5/32) were not detectable in DBS, while measurable HIV-1 RNA levels were present in plasma (1.44 to 3.99 logThe performance of the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA using one DBS was acceptable. DBS, as an alternative sample to plasma, may be a viable option for the simultaneous detection of HIV-1 RNA, HIV-1 DNA, and HCV RNA in resource-limited settings or for individuals living in areas that are difficult to access.

Background: Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. Recent studies have shown that phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the survival of fibroblast-like synoviocytes (FLS) and the production of pro-inflammatory cytokines in RA.Methods : The expression was determined in RA and adjuvant-induced arthritis (AIA) synovial tissues by immunohistochemistry. FLSs were treatment with bpv, PTEN-RNAi or over-expression plasmid in RA and AIA. FLSs migration was assessed. The ad-PTEN was also injected into the knee of AIA in vivo. Chromatin Immunoprecipitation (ChIP) and Methylation-special PCR (MSP) assay were used to study the expression of PTEN mRNA in DNA methylation.Results : Down-regulated level of PTEN expression was observed in RA and AIA. Inhibition PTEN expression by bpv or PTEN-RNAi could promote the expression of pro-inflammatory cytokines, chemokines and migration of FLS with TNF-α in RA and AIA. Consistently, over-expression of PTEN reduced their low-expression of pro-inflammatory cytokines, chemokines and migration. Intra-articular injection of ad-PTEN in AIA knees dramatically reduced inflammatory and paw swelling in vivo. The ChIP and MSP assay has clearly detected the DNA methylation of PTEN was increased in FLS with TNF-α. Moreover, intraperitoneally injected 5-Aza in AIA also suppressed the inflammatory and paws swelling in vivo.Conclusions: Our findings suggest that over-expression PTEN attenuates the formation of pro-inflammatory cytokines, chemokines and migration of FLS, and it may be regulated by DNA methylation in the pathogenesis of RA.

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Alzheimer’s disease (AD) is the most common form of dementia characterized by progressive loss of cognitive functions due to neuronal death mainly in the hippocampal and cortical brain. Sulforaphene (SF) is one of the main isothiocyanates isolated from a Chinese herb Raphani Semen. In this study, we aimed to investigate the neuroprotective effects of SF usingin vitroandin vivomodels of AD. Streptozotocin (STZ) was intracranially injected into the rats; then, SF (25 and 50 mg/kg) was given orally once a day for 6 consecutive weeks. After drug treatment, the cognitive functions were assessed using the Morris Water Maze Test (MWMT). After the MWMT, the rats were euthanized and brain tissues were collected. In thein vitrotest, BV-2 microglia were pretreated with SF (1 and 2 μM) for 1 h and then stimulated with lipopolysaccharide (LPS) for another 23 h. Both molecular and histological methods were used to unravel the action mechanisms and elucidate the signaling pathway. The MWMT results showed that SF treatment significantly improved the STZ-induced cognitive deficits in rats. SF treatment markedly suppressed the production of tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) but increased the release of IL-10 in the STZ-treated rats. In addition, SF significantly inhibited the phosphorylation of tau protein at Thr205, Ser396, and Ser404 sites, while enhancing the ratios of p-Akt (Ser473)/Akt and p-GSK-3β(Ser9)/GSK-3βin the hippocampus of the STZ-treated rats. On the other hand, SF (1 and 2 μM) treatment also markedly attenuated the cytotoxicity induced by LPS in BV-2 cells. In addition, SF treatment obviously suppressed the releases of nitric oxide (NO), TNF-α, and IL-6 in the LPS-stimulated BV-2 cells. Moreover, SF treatment significantly mitigated the nuclear translocation of p-NF-κB p65 and the ratio of p-GSK-3β(Ser9)/GSK-3βin LPS-stimulated BV-2 cells. Taken together, SF possessed neuroprotective effects against the STZ-induced cognitive deficits in rats and LPS-induced neuroinflammation in BV-2 cells via modulation of the PI3K/Akt/GSK-3βpathway and inhibition of the NF-κB activation, suggesting that SF is a promising neuroprotective agent worthy of further development into AD treatment.

Background Vascular dementia (VaD) is the second common form of dementia and Chinese herbal medicine (CHM) has been used for aging-related disorders for thousands of years. However, there is still a lack of scientific evidence using CHM for VaD. Objective To conduct a systematic review to assess the current evidence available for the effectiveness and safety of CHM for VaD. Methods Six databases were searched for high-quality randomized-controlled clinical trials that met the requirements of at least 4 of the 7 domains of the Cochrane risk of bias tool from their inception to February 2017. RevMan 5.3 was applied for data analysis. Results Forty studies with 42 comparisons and 3,572 individuals were included. The studies investigated the CHM versus placebo (n = 4), CHM versus western conventional treatment (WCT) (n = 36), and CHM plus WCT versus WCT (n = 2). Meta-analysis showed that CHM for VaD could improve Mini-Mental State Examination (MMSE), the Activities of Daily Living, Hasegawa's dementia scale, and clinical effective rate but had statistically similar effect based on Blessed Behavior Scale (BBS) outcome when compared with WCTs. When compared with placebo, CHMs were more beneficial in improving MMSE but showed no significant difference in BBS scores. CHM as adjuvant therapy exerted an additive anti-VaD benefit on MMSE scores. The participants of CHM group had fewer adverse events than that of the placebo group or WCT group. Conclusion The findings of the present study support, at least to an extent, that CHM can be recommended for routine use for treatment of VaD.