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OBJECTIVE To compare the analgesic effects of two types of spinal manipulation (SM) in acute lumbar radiculopathy (ALR) model rats induced by self-transplantation of autologous nucleus pulposus (ANP), and clarify the therapeutic mechanism. METHODS Totally 108 male Sprague-Dawley rats were randomly divided into 6 groups by a random number table (18 rats in each group), including a blank group with no interference, a sham operation group with a surgery by making a local soft tissue incision on the left side of L5-6 vertebral segment, a model group with ALR of L5 extraforaminal nerve by ANP self-transplantation without other interference, a sham manipulation (SMA) group with simulating physical rotation, as well as a mobilization (MOB) group with simulating low-velocity and variable-amplitude rotation and a manipulation (MAN) group with simulating high-velocity and low-amplitude rotation. The interventions in SMA, MOB, and MAN groups started 1 day after modeling followed by another 5 treatments at days 3, 5, 8, 10 and 12. Rats in the other 3 groups did not receive any special intervention. Behavioral pain tests of 50% mechanical pain withdrawal threshold (50% PWT) and paw withdrawal latency (PWL) were conducted 1 day before operation followed by another 10 tests on days 1-7, 10, 12 and 14. Immunohistochemical expression of nitric oxide synthase (NOS) was investigated on days 5 and 12 after operation. RESULTS After 3 experimental SM interventions, 50% PWT and PWL were higher in the MAN group than the SMA group on days 6 and 7, and higher on days 10, 12 and 14 postoperatively (P

BACKGROUND Time in range (TIR), as a novel metric for glycemic control, has robust relevance with diabetic complications. Diabetic peripheral neuropathy (DPN) is characterized by sudomotor dysfunction. AIM To explore the relationship between TIR obtained from continuous glucose monitoring (CGM) and sudomotor function detected by SUDOSCAN in subjects with type 2 diabetes. METHODS The research enrolled 466 inpatients with type 2 diabetes. All subjects underwent 3-d CGM and SUDOSCAN. SUDOSCAN was assessed with electrochemical skin conductance in hands (HESC) and feet (FESC). Average feet ESC < 60 µS was defined as sudomotor dysfunction (+), otherwise it was sudomotor dysfunction (-). TIR refers to the percentage of time when blood glucose is between 3.9-10 mmol/L during 1 d period. RESULTS Among the enrolled subjects, 135 (28.97%) presented with sudomotor dysfunction. Patients with sudomotor dysfunction (+) showed a decreased level of TIR (P < 0.001). Compared to the lowest tertile of TIR, the middle and the highest tertiles of TIR was associated with an obviously lower prevalence of sudomotor dysfunction (20.51% and 21.94% vs 44.52%) (P < 0.001). In addition, with the increase of TIR, HESC and FESC increased (P < 0.001). Regression analysis demonstrated that TIR was inversely and independently linked with the prevalence of sudomotor dysfunction after adjusting for confounding values (odds ratio = 0.979, 95%CI: 0.971-0.987, P < 0.001). CONCLUSION The tight glycemic control assessed by TIR is of vitally protective value for sudomotor dysfunction in type 2 diabetes mellitus.

Background Time in range (TIR) is advocated as key metric of glycemic control and is reported to be associated with microvascular complications of diabetes. Sudomotor dysfunction is among the earliest detectable diabetic peripheral neuropathy (DPN). We set about to research the relationship between TIR including overnight TIR and sudomotor function detected by SUDOSCAN with the intention of exploring the correlation of TIR including overnight TIR and early DPN in type 1 diabetes (T1D). Methods 95 patients with T1D were enrolled. TIR including nocturnal TIR of 3.9–10.0 mmol/L was evaluated with CGM. SUDOSCAN measured feet electrochemical skin conductance (FESC) and sudomotor dysfunction was defined as average FESC Results The overall prevalence of sudomotor dysfunction was 28.42%. Patients with sudomotor dysfunction had significantly lower TIR for the whole recorded phase and for nighttime. The sudomotor dysfunction prevalence progressively declined with the ascending tertiles of TIR and nocturnal TIR (P for trend Conclusions TIR is negatively correlated with sudomotor dysfunction in T1D independent of HbA1c. Furthermore, decreased nocturnal TIR is more closely related to the impaired function of sudomotor nerves in sweat glands.

Increasing water content in fixed beds is a prospective way to improve the gas storage density by means of hydrate formation. However, the high water content strongly hinders the hydrate formation. In this study, diesel oil was mixed into highly water-saturated activated carbon beds to establish gas channels so that to improve methane hydrate formation. Hydrate formation experiments in four activated carbons with different particle sizes were conducted at 274.15 K and 6.0 MPa. For wet carbon beds without diesel oil, both of the storage capacity of hydrate (Sw) and the storage density of bed (Sb) increased with an decrease in particle size. When the mass ratio of water to activated carbon was set to 2.0, the highest Sw of 67.98 V/Vw and corresponding Sb of 51.92 V/Vbed among the beds were obtained in the bed with particle size of 100–400 mesh. Sodium dodecyl sulfate (SDS) was found to suppress hydrate formation in fine-particle beds. By adding diesel oil, both the formation kinetics and Sw in highly water-saturated beds especially in small-particle ones were significantly improved. The Sw and Sb in the bed with particle size of 100–400 mesh were increased to 180.41 V/Vw and 111.75 V/Vbed, respectively. Furthermore, by adjusting the proportions of water, oil and activated carbon in the bed, the Sw was further improved. The successive gas storage tests suggested that the oil-contained bed can be simply renewed by manual stirring. Gas recovery experiments showed that the hydrate dissociated faster in the oil-contained bed than that in SDS solution, suggesting more efforts should be made to control the hydrate dissociation to drive this method into practical application.

Bone-related malignancies, such as osteosarcoma, Ewing’s sarcoma, multiple myeloma, and cancer bone metastases have similar histological context, but they are distinct in origin and biological behavior. We hypothesize that a distinct immune infiltrative microenvironment exists in these four most common malignant bone-associated tumors and can be used for tumor diagnosis and patient prognosis. After sample cleaning, data integration, and batch effect removal, we used 22 publicly available datasets to draw out the tumor immune microenvironment using the ssGSEA algorithm. The diagnostic model was developed using the random forest. Further statistical analysis of the immune microenvironment and clinical data of patients with osteosarcoma and Ewing’s sarcoma was carried out. The results suggested significant differences in the microenvironment of bone-related tumors, and the diagnostic accuracy of the model was higher than 97%. Also, high infiltration of multiple immune cells in Ewing’s sarcoma was suggestive of poor patient prognosis. Meanwhile, increased infiltration of macrophages and B cells suggested a better prognosis for patients with osteosarcoma, and effector memory CD8 T cells and type 2 T helper cells correlated with patients’ chemotherapy responsiveness and tumor metastasis. Our study revealed that the random forest diagnostic model based on immune infiltration can accurately perform the differential diagnosis of bone-related malignancies. The immune microenvironment of osteosarcoma and Ewing’s sarcoma has an important impact on patient prognosis. Suppressing the highly inflammatory environment of Ewing’s sarcoma and promoting macrophage and B cell infiltration may have good potential to be a novel adjuvant treatment option for osteosarcoma and Ewing’s sarcoma.

Background: The treatment of pulmonary malignancies remains a challenge. The efficacy and safety of bronchoscopic radiofrequency ablation (RFA) for the treatment of lung cancer are not well elucidated. Objective: This study aimed to evaluate the feasibility and safety of RFA guided by bronchoscopic transparenchymal nodule access (BTPNA) in vivo. Methods: In an attempt to determine the parameters of RFA, we first performed RFA in conjunction with automatic saline microperfusion in the lung in vitro with various ablation energy (10, 15, 20, 25, and 30 W) and ablation times (3, 5, 8, and 10 min). The correlation between ablated area and RFA parameter was recorded and analyzed. Further, we conducted a canine study with RFA by BTPNA in vivo, observing the ablation effect and morphological changes in the lung assessed by chest CT and histopathologic examination at various follow-up time points (1 day, n = 3; 30 days, n = 4; 90 days, n = 4). The related complications were also observed and recorded. Results: More ablation energy, but not ablation time, induced a greater range of ablation area in the lung. Ablation energy applied with 15 W for 3 min served as the appropriate setting for pulmonary lesions ≤1 cm. RFA guided by BTPNA was performed in 11 canines with 100% success rate. Inflammation, congestion, and coagulation necrosis were observed after ablation, which could be repaired within 7 days; subsequently, granulation and fibrotic scar tissue developed after 30 days. No procedure-related complication occurred during the operation or in the follow-up periods. Conclusion: The novel RFA system and catheter in conjunction with automatic saline microperfusion present a safe and feasible modality in pulmonary parenchyma. RFA guided by BTPNA appears to be well established with an acceptable tolerance; it might further provide therapeutic benefit in pulmonary malignancies.

Background To assist doctors to diagnose mild cognitive impairment (MCI) and Alzheimer's disease (AD) early and accurately, convolutional neural networks based on structural magnetic resonance imaging (sMRI) images have been developed and shown excellent performance. However, they are still limited in their capacity in extracting discriminative features because of large sMRI image volumes yet small lesion regions and the small number of sMRI images. Methods We proposed a task-driven hierarchical attention network (THAN) taking advantage of the merits of patch-based and attention-based convolutional neural networks for MCI and AD diagnosis. THAN consists of an information sub-network and a hierarchical attention sub-network. In the information sub-network, an information map extractor, a patch-assistant module, and a mutual-boosting loss function are designed to generate a task-driven information map, which automatically highlights disease-related regions and their importance for final classification. In the hierarchical attention sub-network, a visual attention module and a semantic attention module are devised based on the information map to extract discriminative features for disease diagnosis. Results Extensive experiments were conducted for four classification tasks: MCI versus (vs.) normal controls (NC), AD vs. NC, AD vs. MCI, and AD vs. MCI vs. NC. Results demonstrated that THAN attained the accuracy of 81.6% for MCI vs. NC, 93.5% for AD vs. NC, 80.8% for AD vs. MCI, and 62.9% for AD vs. MCI vs. NC. It outperformed advanced attention-based and patch-based methods. Moreover, information maps generated by the information sub-network could highlight the potential biomarkers of MCI and AD, such as the hippocampus and ventricles. Furthermore, when the visual and semantic attention modules were combined, the performance of the four tasks was highly improved. Conclusions The information sub-network can automatically highlight the disease-related regions. The hierarchical attention sub-network can extract discriminative visual and semantic features. Through the two sub-networks, THAN fully exploits the visual and semantic features of disease-related regions and meanwhile considers global features of sMRI images, which finally facilitate the diagnosis of MCI and AD.

The toxicity of hydrate inhibitors used in the field has attracted more attention. A natural material, i.e., whey protein, was assessed to act as kinetic hydrate inhibitors (KHIs) in a sapphire cell and an autoclave equipped with particle video microscope (PVM) and focused beam reflectance measurement (FBRM) probes. The pressure dropping method was utilized to estimate the hydrate induction time, and the results demonstrate that the hydrate inhibition performance of whey protein is superior to that of the commercial KHI, polyvinylpyrrolidone. The induction time for the pure water system was found to increase linearly with the increase in the dosage of whey protein until it reached approximately 2.5 wt%. As it is usually inevasible to apply KHIs under conditions of high water contents, the feasibility of whey protein as a KHI in the (oil + water) system with and without an emulsifier of Tween 20 was evaluated. A small amount of oil was found to have no obvious influence on the induction time for the system with whey protein under the circumstances without the addition of emulsifier. When Tween 20 was added, the induction time obviously increased under the same operating conditions, which could be attributed to the emulsifier–protein interactions in aqueous solutions. The oil drops decrease and are distributed more evenly with the increasing dosage of Tween 20 under the PVM and FBRM probes measurement. Additionally, the particles decrease during the hydrate formation process. This work presents a natural KHI and gives the inhibition discipline in a high-water-content system.

Porous materials are deemed to be capable for promoting hydrate formation, while for the purpose of hydrate-based gas storage, those systems containing porous materials often cannot meet the requirement of high storage density. To increase the storage density, an adsorption-hydration sequence method was designed and systematically examined in this study. Methane storage and release in ZIF-8 slurries and fixed beds were investigated. The ZIF-8 retained 98.62%, while the activated carbon lost 62.17% of their adsorption capacities in slurry. In ZIF-8 fixed beds, methane storage density of 127.41 V/Vbed was acquired, while the gas loss during depressurization accounted for 21.50% of the gas uptake. In the ZIF-8 slurry, the storage density was effectively increased with the adsorption-hydration sequence method, and the gas loss during depressurization was much smaller than that in fixed beds. In the slurry, the gas uptake and gas loss decreased with the decrease of the chilling temperature. The largest gas uptake and storage density of 78.84 mmol and 133.59 V/Vbed were acquired in the slurry with ZIF-8 content of 40 wt.% at 268.15 K, meanwhile, the gas loss just accounted for 14.04% of the gas uptake. Self-preservation effect was observed in the slurry, and the temperature for the slowest gas release was found to be 263.15 K, while the release ratio at 10 h reached to 43.42%. By increasing the back pressure, the gas release rate could be effectively controlled. The gas release ratio at 1.1 MPa at 10 h was just 11.08%. The results showed that the application of adsorption-hydration sequence method in ZIF-8 slurry is a prospective manner for gas transportation.

Yan-Rong Zhao,1 Hao Liu,2 Li-Miao Xiao,3 Can-Guang Jin,1 Zhi-Peng Zhang,1 Chun-Guang Yang4 1Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; 2Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; 3Department of Ultrasound, Hunan Children’s Hospital, Changsha, Hunan, China; 4Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China Purpose: The identification and discovery of prognostic markers for colorectal cancer (CRC) are of great clinical significance. CCBE1 is expressed in various tumors and its expression correlates with lymphangiogenesis and angiogenesis. However, the association between CCBE1 expression and CRC outcome has not been reported. The aim of this study was to investigate clinical significance of CCBE1 expression in CRC. Patients and methods: CCBE1 expression was examined in 30 pairs of fresh CRC tissues and compared with adjacent normal (AN) tissues using quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry (IHC) staining. Tissue microarray immunohistochemical staining was used to study the CCBE1 expression characteristics of 204 CRC patient samples collected from January 2002 to December 2007, and the relationship of CCBE1 with clinicopathological features and prognosis of CRC was analyzed. Results: CCBE1 was highly expressed in CRC tissues compared with matched AN tissues (P=0.001). Moreover, high expression of CCBE1 was significantly associated with tumor differentiation, lymph node metastasis, vascular invasion, liver metastasis and TNM stage in CRC patients (P≤0.01). Kaplan–Meier survival analysis revealed that high CCBE1 expression, poor tumor differentiation, lymph node metastasis and vascular invasion were significantly associated (allP

Traumatic brain injury (TBI) is to date one of the major critical conditions causing death and disability worldwide. Exogenous neural stem/precursor cells (NSCs/NPCs) hold great promise for improving neurological dysfunction, but their functional properties in vivo remain unknown. Human neural precursor cells (hNPCs) carrying one fluorescent reporter gene (DsRed) can be observed directly in vivo using two-photon laser-scanning microscope. Therefore, we evaluated the neural integration and potential therapeutic effect of hNPCs on mice with TBI. Behavioral tests were performed by rotarod task and Morris Water Maze task. Neural integration was detected by fluorometric Ca2+ imaging and nerve tracing. We found that motor and cognition functions were significantly improved in mice with hNPCs injection compared to mice with vehicle treatment, and hNPCs integrated into the host circuit and differentiated toward neuronal lineage. Our study provided reliable evidence for further hNPCs transplantation in clinical practice.

Rapamycin is known to inhibit the mammalian target of rapamycin complex (mTORC)1 signaling pathway, but it is unable to effectively inhibit mTORC2, resulting in activation of protein kinase B in multiple myeloma (MM) cell lines. Additionally, certain studies have suggested that resveratrol has an effect on human MM cells, and that rapamycin in combination with resveratrol may be useful in cancer therapy. The present study aimed to investigate the combined treatment effect of resveratrol and rapamycin on the MM MM1.S cell line. The results demonstrated that combined treatment with rapamycin and resveratrol effectively inhibited cell viability in the MM1.S cell line through inhibition of the mTORC1 and mTORC2 signaling pathways, compared with resveratrol or rapamycin monotherapy. In addition, cyclin D1 levels were decreased and the activation of caspase-3 and poly (ADP-ribose) polymerase was increased. These results suggested that downregulation of the mTOR signaling cascades is likely to be a crucial mediator in the impairment of viability and the induction of apoptosis resulting from combined therapy with resveratrol and rapamycin in MM1.S cells.

Aim: The aim of the study is to analyze the safety and efficacy of low-dose transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Materials and Methods: Seventy-five HCC patients with PVTT, who were admitted to our hospital between 2011 and 2015 and underwent TACE, were analyzed. The safety and efficacy of low-dose TACE were evaluated. Results: The objective tumor response rate was 25.3%. The median overall survival time was 10.7 months (95% confidence interval [CI]: 8.2–13.2). The cumulative survival rates at 6, 12, 18, and 24 months were 65.3%, 44%, 17.3%, and 2.6%, respectively. Univariate analysis revealed that alpha-fetoprotein (heart rate [HR] = 1.307, 95% CI: 1.019–1.427,P < 0.05), Child–Pugh classification (HR = 2.984, 95% CI: 1.741–5.115, P < 0.001), PVTT (HR = 3.409, 95% CI: 2.745–4.512, P < 0.001), number of tumor (HR = 2.358, 95% CI: 1.956–3.375, P < 0.001), and size of tumor (HR = 2.301, 95% CI: 1.667–3.268, P < 0.001) were related with survival. In multivariate analysis, Child–Pugh classification (HR = 2.351, 95% CI: 1.256–4.215, P < 0.001), type of PVTT (HR = 2.749, 95% CI: 2.238–3.961, P < 0.001), number of tumor (HR = 1.795, 95% CI: 1.521–3.046, P < 0.001), and size of tumor (HR = 1.917, 95% CI: 1.379–3.057, P = 0.03) were independent predictive factors for survival rates. The incidence of complications due to procedures was 85.3%. Conclusion: The low-dose TACE may be considered selectively to HCC patients with PVTT. Child–Pugh classification, type of PVTT, number of tumor, and size of tumor were checked accurately before operation.

Hepatocellular carcinoma (HCC) represents a serious public health challenge with few therapeutic options available to cancer patients.Wnt/β-catenin pathway is thought to play a significant role in HCC pathogenesis. In this study, we confirmed high frequency of CTNNB1 (β-catenin) mutations in two independent cohorts of HCC patients and demonstrated significant upregulation of β-catenin protein in the overwhelming majority of HCC patient samples, patient-derived xenografts (PDX) and established cell lines. Using genetic tools validated for target specificity through phenotypic rescue experiments, we went on to investigate oncogenic dependency on β-catenin in an extensive collection of human HCC cells lines. Our results demonstrate that dependency on β-catenin generally tracks with its activation status. HCC cell lines that harbored activating mutations in CTNNB1 or displayed elevated levels of non-phosphorylated (active) β-catenin were significantly more sensitive to β-catenin siRNA treatment than cell lines with wild-type CTNNB1 and lower active β-catenin. Finally, significant therapeutic benefit of β-catenin knock-down was demonstrated in established HCC tumor xenografts using doxycycline-inducible shRNA system. β-catenin downregulation and tumor growth inhibition was associated with reduction in AXIN2, direct transcriptional target of β-catenin, and decreased cancer cell proliferation as measured by Ki67 staining. Taken together, our data highlight fundamental importance of aberrant β-catenin signaling in the maintenance of oncogenic phenotype in HCC.

As the main organic pollutants in wastewater, antibiotics and organic dyes are harmful to the environment and public health, and their removal is important but challenging. In this work, highly porous 3D metal-organic frameworks (MOFs) [M2 (PDAD)(H2 O)]n (PCN-124-stu; M=Cu, Zn; H4 PDAD = 5,5'-(pyridine-3,5-dicarbonyl)bis(azanediyl)diisophthalic acid) were synthesized, and PCN-124-stu(Cu) shows excellent chemical and thermal stability. PCN-124-stu(Cu) was used as a host for efficient extraction of various organic dyes, especially the large-molecule dye Coomassie brilliant blue, and fluoroquinolones from water, in comparison with five common MOFs, zeolite 13X, and activated carbon. PCN-124-stu(Cu) exhibits absolute predominance for fluoroquinolone adsorption among these microporous materials because of the H-bonds between fluoroquinolone molecules and the amide groups in the frameworks, except for MIL-100(Cr), which is a mesoporous MOF. Moreover, PCN-124-stu(Cu) could release fluoroquinolones slowly in physiological saline and retained its framework structure after four adsorption/desorption cycles. In addition, PCN-124-stu(Cu) can be used as a platform for selective adsorption of CO2 /CH4.

Flexure hinges have been widely used in space-borne telescopes for mounting reflective optics with high surface figure requirements. To realize the three-point flexural mount of a Φ750 mm primary mirror, a Cartwheel biaxial flexural hinge composed by filleted short beams is proposed and the dimensionless design graph method for the flexural hinge is presented. The finite element analysis is performed on the flexure model to validate the proposed method. We also demonstrate the feasibility of the proposed method experimentally. The maximum relative error of the rotational stiffness between analysis, testing result, and design value is 5.0%. The proposed dimensionless design graph can be used as a design tool to determine the optimal geometry of a spatial flexure hinge rapidly.

Recently, two derivatives of PVP named PVP-A and PVP-E were synthesized by our group and PVP-A was verified to have good inhibition performance by experiments. PVP-A and PVP-E were obtained by introducing a butyl ester group and a butyl ether group into PVP molecules, respectively. In this work, the inhibition process of hydrate growth at molecular level was simulated to explore the inhibition performance of PVP-A, PVP-E, and PVP and clarified their inhibition mechanism. Our simulation results show that PVP-A has the best inhibition performance among these selected KHIs which was in accordance with experiments. The binding interactions between inhibitors and liquid water molecules play a significant role in inhibition performance of KHIs. The strong binding effect could greatly disrupt the hydrogen-bond structure between the water molecules in the vicinity of hydrate nucleus surface and attract more water molecules to form hydrogen bond with KHIs rather than build hydrate clathrate on the surface of hydrate nucleus and therefore prevents the hydrate nucleus reaching the critical nuclear size for subsequent spontaneous growth.

Chromosomal abnormalities such as aneuploidies and DNA damage are considered a major threat to the establishment of healthy eggs and embryos. Recent landmark studies showed that mouse oocytes with damaged DNA can resume meiosis and undergo Germinal Vesicle Breakdown (GVBD), but then arrest in metaphase of meiosis-I in a process involving Spindle Assembly Checkpoint (SAC) signalling. Such a mechanism could help prevent the generation of metaphase-II (Met-II) eggs with damaged DNA. However we report that this is not the case in the human oocyte. DNA damage prevents human oocytes from undergoing GVBD in some cases. Strikingly however, most oocytes harbouring DNA damage progress through meiosis-I and subsequently extrude the first polar body (PB1) to form a metaphase-II egg, revealing the absence of a DNA-damage-induced SAC response. Analysis of the resulting metaphase-II eggs revealed highly disorganised spindles with misaligned and heavily damaged chromosomes. Our results suggest that DNA damage accumulated in meiosis-I, such as could occur during in vitro maturation procedures, does not prevent polar body extrusion and therefore could persist in morphologically normal looking metaphase-II eggs.

Federal guidelines recommend that food with hormone content fall below 1% of endogenous production in the subset of the population with the lowest daily production. The majority of dairy products are obtained from pregnant cows, which increase the level of hormones present. The purpose of this article was to perform theoretical evaluation of the quantity of progesterone in cow's milk based on fat percentages and to assess whether this was within the recommended range. Daily recommended dairy product intake from various countries worldwide was researched. This was compared to the concentration of progesterone previously identified in varying fat contents of cow origin milk to assess the amount of progesterone (mg/day) that would be consumed if the guidelines were followed. The maximum daily progesterone consumption suggested will be met by ingestion of 2.7 L, 1.42 L, 1.13 L, 940 mL, 810 mL, 650 mL of 0% (skim), 1%, 2%, 3.25%, 10% (cream), and 35% (whipping cream) fat liquid cow origin dairy product, respectively. Therefore, ingestion of the highest amount of recommended daily dairy intake fell below 1% of the daily endogenous quantity produced, except in the unlikely case of consumption of 650 mL of 35% fat. Studies demonstrating an effect of cow's liquid dairy product intake may need to be revisited, since levels of progesterone consumption remain within the recommended levels. However, it should be considered that ingestion of cow's milk might have a potential effect on the hormonal profile in patients; however, this seems unlikely.

Progressive diabetic nephropathy (DN) in diabetes leads to major morbidity and mortality. The major pathological alterations of DN include mesangial expansion, extracellular matrix alterations, tubulointerstitial fibrosis, and glomerular sclerosis. Polygoni avicularis is widely used in traditional oriental medicine and has long been used as a diuretic, astringent, insecticide and antihypertensive. However, to the best of the authors’ knowledge, the effects of the ethanolic extract from rhizome of Polygoni avicularis (ER-PA) on DN have not yet been assessed. The present study aimed to identify the effect of ER-PA on renal dysfunction, which has been implicated in DN in human renal mesangial cells and db/db mice and investigate its mechanism of action. The in vivo experiment was performed using Polygoni avicularis-ethanol soluble fraction (ER-PA) and was administrated to db/db mice at 10 and 50 mg/kg dose. For the in vitro experiments, the human renal mesangial cells were induced by high glucose (HG, 25 mM). The ER-PA group showed significant amelioration in oral glucose tolerance, and insulin resistance index. ER-PA significantly improved the albumin excretion and markedly reduced plasma creatinine, kidney injury molecule-1 and C-reactive protein. In addition, ER-PA significantly suppressed inflammatory cytokines. Histopathologically, ER-PA attenuated glomerular expansion and tubular fibrosis in db/db mice. Furthermore, ER-PA suppressed the expression of renal fibrosis biomarkers (TGF and Collagen IV). ER-PA also reduced the NLR family pyrin domain containing 3 inflammatory factor level. These results suggest that ER-PA has a protective effect against renal dysfunction through improved insulin resistance as well as the inhibition of nephritis and fibrosis in DN.

Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury. There is currently no proven pharmacologic treatment for TBI+HS, but modulation of the epigenome has been shown to be a promising strategy. The aim of this study was to investigate whether valproic acid (VPA), a histone deacetylase inhibitor, modulates the expression of cerebral inflammatory gene profiles in a large animal model of TBI+HS. Ten Yorkshire swine were subjected to computer-controlled TBI+HS (40% blood volume). After 2 h of shock, animals were resuscitated with Hextend (HEX) or HEX+VPA (300 mg/kg, n = 5/group). Six hours after resuscitation, brains were harvested, RNA was isolated, and gene expression profiles were measured using a porcine microarray. Ingenuity Pathway Analysis® (IPA), gene ontology (GO), Parametric Gene Set Enrichment Analysis (PGSEA), and DAVID (Database for Annotation, Visualization, and Integrated Discovery) were used for pathway analysis. Key microarray findings were verified using real-time polymerase chain reaction (PCR). IPA analysis revealed that VPA significantly down-regulated the complement system (p

Background Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). Objectives To determine the efficacy and safety of para -toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. Methods Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. Results In full-analysis set ( N =88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%–69.5%), bronchoscopy: 48.9% (95%CI: 38.1%–59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%–54.2%), bronchoscopy: 29.6% (95%CI: 20.3%–40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16–0.53 liters), FEV 1 (mean difference: 0.27 liters, 95%CI: 0.07–0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9–74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6·9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9–10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). Conclusion PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO.

Developing reliable and user-friendly electroencephalography (EEG) electrodes remains a challenge for emerging real-world EEG applications. Classic wet electrodes are the gold standard for recording EEG; however, they are difficult to implement and make users uncomfortable, thus severely restricting their widespread application in real-life scenarios. An alternative is dry electrodes, which do not require conductive gels or skin preparation. Despite their quick setup and improved user-friendliness, dry electrodes still have some inherent problems (invasive, relatively poor signal quality, or sensitivity to motion artifacts), which limit their practical utilization. In recent years, semi-dry electrodes, which require only a small amount of electrolyte fluid, have been successfully developed, combining the advantages of both wet and dry electrodes while addressing their respective drawbacks. Semi-dry electrodes can collect reliable EEG signals comparable to wet electrodes. Moreover, their setup is as fast and convenient similar to that of dry electrodes. Hence, semi-dry electrodes have shown tremendous application prospects for real-world EEG acquisition. Herein, we systematically summarize the development, evaluation methods, and practical design considerations of semi-dry electrodes. Some feasible suggestions and new ideas for the development of semi-dry electrodes have been presented. This review provides valuable technical support for the development of semi-dry electrodes toward emerging practical applications.

Glomerular fibrosis is caused by an accumulation of intercellular spaces containing mesangial matrix proteins through either diffused or nodular changes. Dianthus superbus has been used in traditional medicine as a diuretic, a contraceptive, and an anti-inflammatory agent. The aim of this study was to investigate the effects of Dianthus superbus-EtOAc soluble fraction (DS-EA) on glomerular fibrosis and renal dysfunction, which has been implicated in diabetic nephropathy in human renal mesangial cells and db/db mice. DS-EA was administered to db/db mice at 10 or 50 mg/kg/day for 8 weeks. DS-EA treatment significantly ameliorated blood glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) index, and HbA1c in diabetic mice. DS-EA decreased albumin excretion, creatinine clearance (Ccr), and plasma creatinine levels. DS-EA also ameliorated the levels of kidney injury molecules-1 (KIM-1) and C-reactive protein. DS-EA reduced the periodic acid-Schiff (PAS) staining intensity and basement membrane thickening in glomeruli of the diabetic nephropathy model. In addition, DS-EA suppressed transforming growth factor-&beta, (TGF-&beta, )/Smad signaling. Collagen type IV, a glomerular fibrosis biomarker, was significantly decreased upon DS-EA administration. DS-EA pretreatment attenuated levels of inflammation factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). DS-EA inhibited the translocation of nuclear factor kappa B (NF-&kappa, B) in Angiotensin II (Ang II)-stimulated mesangial cells. These findings suggest that DS-EA has a protective effect against renal inflammation and fibrosis. Therefore, DS-EA may serve as a potential therapeutic agent targeting glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.

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The present study investigated the expression and potential influence of SHC SH2 domain-binding protein 1 (SHCBP1) in gastric cancer (GC) cells. SHCBP1 is closely related to cell proliferation and cell cycle progression, but its role in GC remains unclear. The TCGA database revealed that SHCBP1 is highly expressed in GC tissues. Furthermore, SHCBP1 was revealed to be highly expressed in GC cell lines MGC-803 and SGC-7901 cells, and downregulation of SHCBP1 significantly inhibited GC cell proliferation. Furthermore, SHCBP1 expression promoted cell cycle progression and inhibition of apoptosis. Since the CDK4, cyclin D1 and caspase family proteins play important roles in cell cycle and apoptosis regulation, it was examined whether there was an association between SHCBP1 and these signaling pathways in GC. Our results revealed that SHCBP1 promoted cell cycle progression by regulating the CDK4-cyclin D1 cascade and suppressed caspase-3, caspase PARP-dependent apoptotic pathways. Cell invasion and metastasis experiments also revealed that SHCBP1 promoted tumor growth and invasiveness. These tumor-promoting functions of SHCBP1 may provide a potential molecular basis for the diagnosis and targeted therapy of GC.

In view of their increasing popularity, humidifiers have become a public concern due to their effects on human health. It has been proved that cleaning humidifiers infrequently is associated with humidifier lung and humidifier fever and the use of home humidifier detergent, which is used to prevent the microbes of humidifiers, could lead to a further lung injury. As susceptible populations, children are highly sensitive to changes in the environment. The aim of this article, which is a part of an epidemiological multiple-centre study of asthma and allergies among children (China, Children, Homes, Health, CCHH), is to investigate the association of home humidifier and pre-school children’s eczema in Baotou, China. A cross-sectional study of 5076 children aged 3–7 (79.3% response rate) selected randomly from 37 kindergartens in Baotou was implemented in March to July 2014. A Chi-square test was used in the univariate analysis of the related risk factors of home humidifier use. The associations between children’s eczema and home humidifier use and dampness signs were performed by multiple logistic regressions after adjusting gender, age, family allergic history, currently smoking and house site. Our survey indicated that 52.8% of the parents reported using humidifiers in their houses. Humidifiers were more frequently used in the families with allergic history, higher family income, higher the degree of the mother, larger house area and younger house age. Children receiving antibiotic treatment utilized humidifiers more often than those never receiving antibiotic treatment. Moreover, cleaning frequency, sensation of dry air, indoor comfort in winter and air cleaner use were related to the use of humidifiers. We found that the prevalence of children’s doctor-diagnose eczema in Baotou was 33.7%. Eczema symptoms first appearing during the first year of life occurred in 68.9% of children with eczema. Boys had more eczema than girls and low age children had more eczema than high age children ( P P

We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, brain oxygenation, and intracranial pressure (ICP) and subjected to computer-controlled TBI and multi-system trauma (rib fracture, soft-tissue damage, and liver injury) as well as combined free and controlled hemorrhage (40% blood volume). After 2 h of shock (mean arterial pressure, 30-35 mm Hg), animals were resuscitated with normal saline (NS; 3×volume) or FFP (1×volume; n=6/group). Six hours postresuscitation, brains were harvested and lesion size and swelling were evaluated. Levels of endothelial-derived vasodilator endothelial nitric oxide synthase (eNOS) and vasoconstrictor endothelin-1 (ET-1) were also measured. FFP resuscitation was associated with reduced brain lesion size (1005.8 vs. 2081.9 mm(3); p=0.01) as well as swelling (11.5% vs. 19.4%; p=0.02). Further, FFP-resuscitated animals had higher brain oxygenation as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4 ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage, and TBI. This is associated with a favorable brain oxygenation and cerebral perfusion pressure profile as well as higher levels of endothelial-derived vasodilator eNOS, compared to normal saline resuscitation.

To improve the stratum mechanical properties and prevent the geological disaster, we present a new approach by executing CH4 hydrate exploitation and CO2 sequestration below the freezing point of water to maintain the stratum stiffness during and after hydrate exploitation. An experimental method to clearly show the evolution of the stratum mechanical properties was built and a series of experiments were conducted to simulate the CH4 exploitation and CO2 sequestration process below and above the freezing point of water. The stratum stiffness was found to be maintained during the whole hydrate exploitation process when below the freezing point. Moreover, the presence of ice improves the stratum stiffness due to cementing the sandy grain. The CO2 injection into the hydrate-bearing sediments would further enhance the mechanical properties and realize a CO2 geological sequestration. Compared with hydrate exploitation above the freezing point, the CH4 recovery efficiency is a little lower when under below the freezing point and it decreased with the increased hydrate saturation due to the CH4 hydrate being surrounded by the generation of ice from hydrate dissociation. This phenomenon could be modified by injecting CO2, from which the CH4 recovery efficiency obviously improved for hydrate exploitation below the freezing point.

The second Songhua River has severe organic contamination due to domestic sewage and industrial wastewater. It is important to determine its genotoxic activity, which is a potential hazard for human health. The micronucleus assay and lymphocytes SCGE assay were employed to examine the genotoxic activity of organic extracts of water samples taken from upstream, midstream and downstream in Jilin City section of the second Songhua River in dry season and in wet season, respectively. Micronucleus assay results showed that there were significant increases in water samples at doses of 25L/kg and 50L/kg. The genotoxicity seemed to be less when compared with the results from dry season to wet season and to be strong from upstream to downstream. A similar result was also obtained in DNA damage on lymphocytes by SCGE assay. These results indicate that the organic extracts of water samples taken from the Songhua River show genotoxic activity. The risks of potential harm for human health in the Songhua River should be studied further.

Polycyclic aromatic hydrocarbon (PAHs), espically benzopyrene (BaP),are the most popular pollutants in surface water,and the adverse effects on male reproductive function have aroused more and more attention. The objective of this study is to confirm BaP regulates testosterone (T) in adult rat Leydig cells and then deserve the effect of BaP on Cx43 between Leydig cells, in order to explore whether the influence of Bap on Leydig cells is via its effect on Cx43. Established the primary culture system Leydig cell, Primary cultured Leydig cells were incubated in the different concentrations (1;10;50ug/ml) of BaP, and DMSO control group. After culturing 24h, the expression of Cx43 on cell membrane were investigated with immunofluorescence and the total Cx43 were evaluated by Western blotting.. The results indicate: comparing with the control group, the expression of Cx43 are suppressed by Bap in a dose-response relationship.

NAD(P)H quinone oxidoreductase-1 (NQO1) is commonly elevated in various types of human cancers, including pancreatic, breast and thyroid cancer, as well as others. However, little is known concerning the status of NQO1 in small cell lung cancer (SCLC). To investigate the clinicopathological significance of NQO1 expression and evaluate its role as a potential prognostic marker in SCLC, protein and mRNA expression levels of NQO1 were determined in four fresh tissue samples of SCLC and paired adjacent non-cancerous tissues using western blotting and real-time qRT-PCR, respectively, and 115 cases of SCLC with strict follow-up were selected for immunohistochemical (IHC) staining of NQO1 protein. The correlation between NQO1 expression and the clinicopathological features of SCLC was evaluated using the Chi-square (χ2) and Fisher's exact tests, survival rates were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In regards to the results, levels of NQO1 protein and mRNA were significantly elevated in the four fresh tissue samples of SCLC compared with levels in the paired adjacent non-cancerous tissues, respectively. IHC analysis showed that the rate of strong positive NQO1 protein expression was significantly higher (48.70%) in SCLC when compared with the rate in either adjacent non-cancerous or normal lung tissues (both P

Background Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS), colloids (Hextend [HEX]), and fresh frozen plasma (FFP) resuscitation are associated with differential effects on coagulation and endothelial systems. Methods We subjected 15 Yorkshire swine to TBI and HS (40% blood volume), and kept in HS for 2 hours before resuscitation with NS, HEX, or FFP. Markers of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1 + 2), and natural anticoagulation (activated protein C [aPC]) were determined in serum and brain whole cell lysates. Results Serum levels of aPC were greater in the NS group (203 ± 30 pg/mL) compared with HEX (77 ± 28 pg/mL; P = .02) and FFP (110 ± 28 pg/mL; P = .09), as was PF 1 + 2 in the brain when compared with FFP (PF 1 + 2, 89 ± 46 vs 37 ± 14 ng/mL; P = .035). Brain E-selectin was greater in the NS group compared with FFP (3.36 ± 0.02 vs 3.31 ± 0.01 ng/mL; P = .029). Circulating ICAM-1 levels were increased in the NS group (151 ± 9 ng/mL) compared with the HEX (100 ± 9 ng/mL; P Conclusion In this clinically realistic large animal model of TBI + HS, NS resuscitation was associated with an early activation of coagulation, natural anticoagulation, and endothelial systems, compared with HEX and FFP.

Background Little is known about the comparative susceptibility and differential pathogenic characteristics of Chinese-origin rhesus macaques upon infection with the chimeric SHIVs most commonly applied in experimental research. Methods In vivo infectivity, viral replication, and disease progression related to SHIV-1157ipd3N4, SHIV-162P3, and SHIV-KB9 infections were assessed after intravenous inoculation of Chinese-origin rhesus macaques (n = 10 each). Results SHIV-KB9-infected monkeys had higher plasma viral loads than those infected with SHIV-1157ipd3N4 or SHIV-162P3 (P

BACKGROUND: Platelet dysfunction following trauma has been identified as an independent predictor of mortality. We hypothesized that fresh frozen plasma (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9% normal saline (NS). METHODS: Twelve swine were subjected to multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth factor β [TGF-β], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity. RESULTS: ADP-induced platelet aggregation was significantly higher in the FFP group (46.3 U vs. 25.5 U, p < 0.01) following resuscitation. This was associated with higher fibrinogen levels (202 mg/dL vs. 80 mg/dL, p < 0.01) but lower endothelial activation (VCAM-1, 1.25 ng/mL vs. 3.87 ng/mL, p = 0.05). Other markers did not differ.After 6 hours of observation, ADP-induced platelet aggregation remained higher in the FFP group (53.8 U vs. 37.0 U, p = 0.03) as was fibrinogen levels (229 mg/dL vs. 153 mg/dL, p < 0.01). Endothelial activation was lower (ICAM-1, 21.0 ng/mL vs. 24.4 ng/mL, p = 0.05), whereas TGF-β levels were higher (2,138 pg/mL vs. 1,802 pg/mL, p = 0.03) in the FFP group. Other markers did not differ. Thromboelastography revealed increased clot strength in the FFP group at both postresuscitation time points. CONCLUSION: Resuscitation with FFP resulted in an immediate and sustained improvement in platelet function and clot strength compared with high-volume NS resuscitation. This was associated with an increase in fibrinogen levels and an attenuation of endothelial activation.

Liver transplantation can lead to post-traumatic stress disorder (PTSD) in recipients, but the risk factors associated with PTSD in living donors are unknown. To investigate this progression in pediatric living donors, a cross-sectional investigation was carried out. All participants completed 2 questionnaires: a PTSD self-rating scale (PTSD-SS) and a validated Chinese version of the Medical Outcomes Study Short Form-36 (SF-36). Clinical and demographic data were collected from medical records and self-report questionnaires. Univariate analysis was conducted to identify statistical differences. The prevalence of full PTSD (all symptom clusters) and partial PTSD (2 out of 3 symptom clusters) was 12.1% and 31.1%, respectively. Those with an educational status of elementary school (P = .001), who were donors to their children (P = .008), who were in the first 6 months after transplant (P

IFN-γ-producing CD4(+) T (Th1) cells and IL-17-producing CD4(+) T (Th17) cells have been found to be involved in multiple malignancies; however, the reciprocal relationship between Th1 and Th17 cells in malignant pleural effusion (MPE) remains to be elucidated.To explore the differentiation and immune regulation of Th1 and Th17 cells in the development of MPE in murine models.The distribution and differentiation of Th1 and Th17 cells in MPE were investigated in IFN-γ(-/-), IL-17(-/-), and wild-type mice. The effects of Th1 and Th17 cells on the development of MPE and the survival of mice bearing MPE were also investigated.We have demonstrated that increased Th1 and Th17 cells could be found in MPE as compared with blood and spleen. Compared with wild-type mice, Th17 cells were markedly augmented in MPE from IFN-γ(-/-) mice, and improved survival could be seen in IFN-γ(-/-) mice. Th1 cell numbers were elevated in MPE from IL-17(-/-) mice, and decreased survival could be seen in IL-17(-/-) mice. The in vitro experiments showed that IFN-γ deficiency promoted Th17-cell differentiation by suppressing the STAT3 pathway and that IL-17 deficiency promoted Th1-cell differentiation by suppressing the STAT1 pathway.In mouse models of MPE, IFN-γ inhibited Th17-cell differentiation, whereas IL-17 inhibited Th1-cell differentiation. IL-17 inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-γ promoted MPE formation and mouse death.

A large number of studies have evaluated the impact of TP53 mutations on the prognosis of patients with non-small cell lung cancer (NSCLC); however, the results of these studies are still controversial. Recently, considerable intratumor heterogeneity for genetic alterations has been demonstrated in various human cancers, including lung cancer. In the present study, we evaluated TP53 mutations in NSCLCs by direct sequencing and observed remarkable variation in the values of relative intensity (RI, the height of the peak of mutated allele/the height of the peak of non-mutated allele) of the mutations. We also examined whether the RI values were associated with intratumor heterogeneity of TP53 mutations. In addition, we evaluated the relationship between TP53 mutations and survival outcome. The patients with a TP53 mutation did not have significantly worse survival compared to those without the mutation. However, when tumors with a TP53 mutation were categorized into two groups, those with a low and those with a high RI, the latter group had significantly worse survival compared to those with wild-type TP53 (adjusted hazard ratio = 2.58, 95% confidence interval = 1.21-5.48, P = 0.01), whereas the former group did not. These results suggest that intratumor genetic heterogeneity may be an important factor in determining the role of TP53 mutations on the prognosis of NSCLC patients.