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Colorectal cancer (CRC) is a common malignant tumor that primarily affects the elderly population. Surgery is one of the main treatment modalities for CRC. Frailty is a prevalent characteristic among the elderly and a leading cause of mortality. The frailty index (FI) is a comprehensive tool for assessing patients' frailty status, quantifying indicators such as weight loss, fatigue, and nutritional status, to reflect the degree of frailty. In recent years, the FI has undergone modifications to more accurately evaluate the risk of surgical complications and prognosis in CRC patients. This review summarizes the methods for frailty assessment, the development and modifications of the FI, and compiles the research findings and applications of the FI in predicting surgical complications, postoperative recovery, and survival rates in CRC patients. Furthermore, limitations in the current modified frailty index (mFI) and future research directions are discussed. This review provides essential references for further understanding the role of frailty in CRC patients and the clinical application of the mFI., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Puerarin (PUE), a flavonoid derivative with vasodilatory effects found in the traditional Chinese medicine kudzu, has anti-sensorineural hearing loss properties. However, the mechanism of its protective effect against ototoxicity is not well understood. In this study, we used in vitro and in vivo methods to investigate the protective mechanism of puerarin against cisplatin (CDDP)-induced ototoxicity. We established an ototoxicity model of CDDP in BALB/c mice and assessed the degree of hearing loss and cochlear cell damage. We used bioinformatics analysis, molecular docking, histological analysis, and biochemical and molecular biology to detect the expression of relevant factors. Our results show that puerarin improved CDDP-induced hearing loss and reduced hair cell loss. It also blocked CDDP-induced activation of TRPV1 and inhibited activation of IP3R1 to prevent intracellular calcium overload. Additionally, puerarin blocked CDDP-stimulated p65 activation, reduced excessive ROS production, and alleviated cochlear cell apoptosis. Our study provides new evidence and potential targets for the protective effect of puerarin against drug-induced hearing loss. Puerarin ameliorates cisplatin-induced ototoxicity and blocks cellular apoptosis by inhibiting CDDP activated TRPV1/IP3R1/p65 pathway, blocking induction of calcium overload and excessive ROS expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Lenvatinib is in a first-line therapy for advanced hepatocellular carcinoma (HCC). However, drug resistance is one of the principal obstacles for treatment failure. The molecular mechanism of Lenvatinib resistance has not been well investigated. Materials and methods: A genome-wide CRISPR/Cas9 knockout screening system was established and bioinformatic analysis was used to identify critical genes associated with Lenvatinib resistance. Cell proliferation assays, colony formation assays and cell migration assays were performed to investigate the effect of drug resistance associated genes, particularly DUSP4, on cancer cell malignant behavior during Lenvatinib treatment. In vivo experiments were conducted by using a xenograft mouse model. Results: We identified six genes that were associated with Lenvatinib resistance in HCC, including DUSP4, CCBL1, DHDH, CNTN2, NOS3 and TNF. DUSP4 was found to be significantly decreased at the mRNA and protein levels in Lenvatinib resistant HCC cells. DUSP4 knockout enhanced HCC cell survival, cell proliferation and migration during Lenvatinib treatment in vitro and in vivo , accompanied by regulation of p-ERK and p-MEK levels. This finding implied that DUSP4 deficiency induced Lenvatinib resistance. Interestingly, DUSP4 deficiency induced Lenvatinib resistance was abrogated by the MEK inhibitor Selumetinib, implying that MEK phosphorylation and DUSP4-inhibition dependent ERK activation were required for drug resistance. Finally, we found that DUSP4 deficiency was associated with HCC prognosis and response to Lenvatinib based on clinical data. Conclusions: DUSP4 deficiency mediates Lenvatinib resistance by activating MAPK/ERK signaling and combination therapy using Lenvatinib and MEK inhibitors may be a promising therapeutic strategy for overcoming Lenvatinib resistance., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Remote ischemic perconditioning (RIPerC) could improve neuronal damage and inhibit inflammation and apoptosis. We conducted an in-depth exploration of the protective mechanism of RIPerC in cerebral ischaemia injury. In this study, a middle cerebral artery occlusion (MCAO) mouse model was built. According to whether to undergo RIPerC treatment and the duration of cerebral infarction, mice were divided into 5 groups: Sham group, MCAO 3.0 h group, MCAO 4.5 h group, MCAO 3.0 h + RIPerC group, and MCAO 4.5 h + RIPerC group. Overexpressed or silenced miR-153-5p was transfected into the cells to analyse the effects of oxygen-glucose deprivation (OGD) treatment on Neuro-2a cell viability, apoptosis, and related gene expressions by performing quantitative real-time polymerase chain reaction (qRT-PCR), MTT assay, flow cytometry, and Western blot. Bioinformatics analysis, qRT-PCR, dual-luciferase experiment, and RNA immunoprecipitation (RIP) were used to screen and verify the miRNA and downstream mRNA-targeted Toll-like receptor 4 (TLR4). The rescue test further verified the effects of the above target genes and miR-153-5p on the apoptosis of OGD-injured cells, apoptosis-related proteins, and the p65/IkBa pathway. The plasma levels of miR-153-5p in 68 patients with ischaemic stroke were detected within 6 hours of onset, and the patients were followed up for 3 months. We found that, in in vivo studies, RIPerC treatment inhibits cerebral infarction volume and neurological damage, and promotes the expression of miR-153-5p in the MCAO animal model. The expression of miR-153-5p in OGD cells was inhibited, and its upregulation protected Neuro-2a cells. TLR4 was predicted to be the target gene of miR-153-5p and could offset the effect of miR-153-5p mimic on OGD cell protection after up-regulating TLR4. TLR4 overexpression promoted the activation of OGD on the p65/IkBa pathway. Compared with the high plasma miR-153-5p group, the 3-month overall survival rate of patients with ischaemic stroke in the low plasma miR-153-5p group was significantly lower (c2 = 5.095, p = 0.024). In conclusion, RIPerC intervention inhibits the damage caused by cerebral ischaemia partially through the miR-153-5p/TLR4/p65/IkBa signalling pathway.

The South China Sea (SCS) is a highly semi-enclosed marginal sea located in the East Asian monsoon region. This paper proposes interesting aspects of the unique feature of the SCS waves in response to tropical cyclone's passage when large-scale winter monsoon winds prevail. We use the wave model WaveWatch III to study the wave characteristics of typhoon Durian (2006) passing over the middle of SCS in early December 2006, and state the new understanding acquired in the aspects of the tropical cyclone generated waves in the SCS during winter monsoon surge. In light of this, the role of the large-scale NE monsoon winds on winter typhoon wave field characteristics in the SCS are highlighted by conducting sensitivity experiments with and without the NE monsoon winds. The NE monsoon winds weakly affect the SWH field near the typhoon track and strongly away from the track, especially in the deep water area of the northern SCS where the NE monsoon winds produce high waves. Comparisons between the two experiments show the effect of the NE monsoon winds on the directional wave spectra in the SCS, suggesting that the monsoon-generated swells do not decay and remain throughout the typhoon period.

Pulmonary vascular remodeling is the most important pathological characteristic of pulmonary arterial hypertension (PAH). No effective treatment for PAH is currently available because the mechanism underlying vascular remodeling is not completely clear. CD248, also known as endosialin, is a transmembrane protein that is highly expressed in pericytes and fibroblasts. Here, we evaluated the role of CD248 in pulmonary vascular remodeling and the processes of PAH pathogenesis. Activation of CD248 in pulmonary artery smooth muscle cells (PASMCs) was found to be proportional to the severity of PAH. CD248 contributed to platelet-derived growth factor-BB (PDGF-BB)-induced PASMC proliferation and migration along with the shift to more synthetic phenotypes. In contrast, treatment with Cd248 siRNA or the anti-CD248 therapeutic antibody (ontuxizumab) significantly inhibited the PDGF signaling pathway, obstructed NF-κB p65-mediated transcription of Nox4, and decreased reactive oxygen species production induced by PDGF-BB in PAMSCs. In addition, knockdown of CD248 alleviated pulmonary vascular remodeling in rat PAH models. This study provides novel insights into the dysfunction of PASMCs leading to pulmonary vascular remodeling, and provides evidence for anti-remodeling treatment for PAH via the immediate targeting of CD248., (© 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Cisplatin (CDDP) is widely used in clinical settings for the treatment of various cancers. However, ototoxicity is a major side effect of CDDP, and there is an associated risk of irreversible hearing loss. We previously demonstrated that CDDP could induce ototoxicity via activation of the transient receptor potential vanilloid receptor 1 (TRPV1) pathway and subsequent induction of oxidative stress. The present study investigated whether ursolic acid (UA) treatment could protect against CDDP‑induced ototoxicity. UA is a triterpenoid with strong antioxidant activity widely used in China for the treatment of liver diseases. This traditional Chinese medicine is mainly isolated from bearberry, a Chinese herb. The present results showed that CDDP increased auditory brainstem response threshold shifts in frequencies associated with observed damage to the outer hair cells. Moreover, CDDP increased the expression of TRPV1, calpain 2 and caspase‑3 in the cochlea, and the levels of Ca2+ and 4‑hydroxynonenal. UA co‑treatment significantly attenuated CDDP‑induced hearing loss and inhibited TRPV1 pathway activation. In addition, UA enhanced CDDP‑induced growth inhibition in the human ovarian cancer cell line SKOV3, suggesting that UA synergizes with CDDP in vitro. Collectively, the present data suggested that UA could effectively attenuate CDDP‑induced hearing loss by inhibiting the TRPV1/Ca²+/calpain‑oxidative stress pathway without impairing the antitumor effects of CDDP.

MiR-328-3p has been reported to be downregulated and serve as a tumor suppressor in several cancers. Previous studies only have reported the downregulation of miR-328-3p in CRC. However, the roles of miR-328-3p in CRC growth and metastasis were unknown. In this study, we demonstrated that miR-328-3p overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). The PI3K/Akt signaling pathway was also inactivated by miR-328-3p overexpression. MiR-328-3p knockdown showed the opposite effects. In addition, we confirmed that miR-328-3p directly bound to 3'UTR of Girdin and negatively regulated its expression. Girdin knockdown or treatment with PI3K inhibitor LY294002 blocked the effects of miR-328-3p inhibitor on cell proliferation, metastasis, and the PI3K/Akt signaling pathway. Moreover, pre-miR-328 decreased numbers of liver metastatic nodules, and reduced the levels of p-Akt, p-Girdin, and Girdin in metastatic tissues in liver. In conclusion, miR-328-3p may inhibit proliferation and metastasis of CRC cells by targeting Girdin and inactivating the PI3K/Akt signaling pathway. MiR-328-3p may be a novel target in cancer therapy., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

MiR-346-5p is overexpressed in several cancers, including colorectal cancer (CRC). However, the effects of miR-346-5p on CRC progression have not yet been clarified. In our study, miR-346-5p levels in four CRC cell lines and normal human colon epithelial cells were determined by real-time PCR. SW620 and HCT116 cells were selected and then transfected with miR-346-5p mimic, miR-346-5p inhibitor, or specific siRNAs targeting F-box/LRR-repeat protein 2 (FBXL2). Cell proliferation, cell cycle distribution and cell cycle regulators were examined by CCK-8 assay, flow cytometry, and western blot. The binding of miR-346-5p on 3' untranslated region (UTR) of FBXL2 were verified by dual-luciferase reporter assay. CRC cells were co-transfected with miR-346-5p inhibitor and siFBXL2 to investigate the involvement of FBXL2. Interaction of FBXL2 with forkhead box M1 (FoxM1) was examined by co-immunoprecipitation (Co-IP) assay. The effect of miR-346-5p knockdown on CRC tumorigenesis in vivo was investigated. Here, we found that miR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition. Inhibition of FBXL2 showed similar effects as miR-346-5p overexpression. Moreover, we verified that FBXL2 was a direct target of miR-346-5p. FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear β-catenin levels. Additionally, FBXL2 knockdown reversed the effects of miR-346-5p inhibitor. In xenograft models, miR-346-5p knockdown significantly inhibited tumor growth, increased FBXL2 expression, and downregulated the levels of FoxM1 and nuclear β-catenin. In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the β-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the role of Eclipta prostrata (E. prostrata) extract in improving spatial learning and memory deficits in D-galactose-induced aging in rats., Methods: Rats were divided into five groups, with 10 animals in each group. Aging rats were produced by treatment with 100 mg·kg-1·d-1 of D-galactose for 6 weeks. Rats in the E. prostrata treatment groups received an aqueous extract of E. prostrata orally at a concentration of 50, 100, or 200 mg·kg-1·d-1 for 3 weeks. Animals in both the normal and model groups were treated with similar volumes of saline. Spatial memory performance was measured using the Morris water maze. The mRNA levels and enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were analyzed using real-time quantitative PCR and spectrophotometry, respectively. The levels of induced nitric oxide synthase (iNOS), nitric oxide (NO), dopamine (DA), norepinephrine (NE), and serotonin (5-HT) were determined using enzyme-linked immunosorbent assay and spectrophotometry., Results: Compared with the normal group, rats in the D-galactose-treated model group exhibited significant memory loss. There was severe damage to the hippocampal CA1 area, and expression levels of SOD, CAT, GPx, and GR were significantly decreased in the model group compared with the normal group. In the model group, levels of iNOS and NO were significantly increased compared with the normal group. However, treatment with E. prostrata extract reversed the conditions caused by D-galactose-induced aging, especially in the groups with higher treatment concentrations. Compared with the normal group, the levels of DA, NE, and 5-HT were significantly lower in the D-galactose-treated model group. In the E. prostrata extract-treated groups, however, there was a dose-dependent upregulation of DA, NE, and 5-HT expression., Conclusion: Our results suggest that administration of E. prostrata extract can result in an improvement in the learning and memory impairments that are induced by D-galactose treatment in rats. This improvement may be the result of enhanced antioxidative ability, decreased iNOS and NO levels, and the induction of DA, NE, and 5-HT expression in the brain.

Background: The modified early warning score (MEWS) was set up to supply prompt recognition of clinically deteriorating patients before they undergo a severe and life-threatening event. The study aimed to describe the probable usefulness of the MEWS in identifying deteriorating post-Whipple patients in hospital wards., Methods: We performed a study to analyze the relationship between the vital parameters and postoperative severe adverse events of patients after Whipple surgery in Guangdong Provincial People's Hospital from 2000 to 2017. In the retrospective study, a total of 13,651 sets of vital parameters in 236 Whipple postoperative patients were included. Subsequently, we applied a MEWS scoring system and explored the accuracy of the MEWS in evaluating the patients' final events versus advanced mathematical models. We then put the MEWS into the ward warning system and confirmed the accuracy of the MEWS based on the results of prospective studies again., Results: We assessed the ability of the MEWS to predict postoperative complications with an accuracy rate of 90.86-91.23%, a sensitivity of 83.04-90.88%, and a specificity of 90.85-95.73%., Conclusions: The MEWS model was applied to identify post-Whipple patients at risk of complication. Once the MEWS ≥2, interventions were needed to minimize the adverse events. Our data suggest that the MEWS is comparable to the advanced mathematical models, but MEWS is more accessible to perform and more generally applicable., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)

Fresh onions ( Allium cepa L.) emit volatile organic compounds (VOCs) naturally in very low concentrations. The aim of the present study was to determine the emission rate of low-boiling VOCs from healthy and naturally infected onion bulbs at 4, 15, and 25 °C and to evaluate the applicability of the VOC method to monitor quality changes during 12 weeks of storage of two cultivars ('Hystand' and 'Hoza') of yellow onions. VOCs were extracted from the headspace of bulbs by solid phase micro-extraction (SPME) up to 5 times during storage and analyzed by gas chromatography-mass spectrometry (GC-MS). A total of twenty-nine compounds were measured and twenty-seven of these were identified while thirteen were reported for the first time from yellow onion bulbs. Acetone (0.10-18.0 nmol kg -1  day -1 ), dimethyl disulfide (0.12-18.9 nmol kg -1  day -1 ) and hexanal (0.05-4.40 nmol kg -1  day -1 ) were among the most abundant volatiles emitted from healthy bulbs. The concentration of these compounds as well as the total volatiles decreased with time in storage. However, microbial infection resulted in higher emission of propene, carbon disulfide, isoprene, pentane, 2-methylfuran, 3-methylfuran, 1-propenethiol, hexane, and methyl propyl sulfide, indicating that VOC emission may be used as an indicator to monitor natural senescence and decay of stored onion bulbs., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

A long shelf life of onions (Allium cepa L.) is of high importance in the onion industry. Onions are dried and stored in large wooden boxes that are difficult to access. Monitoring temperature and relative humidity during these processes is challenging. Moreover, quality may change in storage without being noticed. Therefore, there is a need to find alternative methods for monitoring and controlling the drying and storage processes of onions and to identify early changes in quality during storage. The potential use of online measurements of temperature and relative humidity (RH) in the vicinity of onions was evaluated during drying and long-term storage of six onion batches (four cultivars and three selections of one of the cultivars) in commercial storage. The batches varied in bulb weight, dry matter content, firmness and disease incidence. The dry matter content and firmness decreased during storage, while the respiration rate and incidences of individual and total disease increased. Two of the batches had low storability with high disease incidences and high average temperatures and variations in the RH. The results showed that tracking the temperature and RH in the vicinity of the onions is a promising tool for improving the drying and storage processes in commercial storage and for identifying onion batches with reduced storability early in storage., Competing Interests: The authors have declared that no competing interests exist.

[This corrects the article DOI: 10.3389/fphar.2018.01226.].

Background: Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of obesity, insulin resistance and cardiovascular diseases (CVDs). Impairment of insulin vascular action may represent a mechanism linking insulin resistance and CVDs. The present study tested the hypothesis that adipocyte-derived resistin inhibits insulin-stimulated endothelial NO production through the induction of ER stress. Methods and Results: Human umbilical vein endothelial cells (HUVC) were incubated with tunicamycin (an inducer of ER stress, 1-20 μg/mL) or resistin (10-100 ng/mL) for 1 h. Either tunicamycin or resistin increased GRP78 (an ER stress marker) expression associated with the impairment of insulin-stimulated Akt/eNOS phosphorylation, which were prevented by TUDCA (an ER stress suppressor). Resistin increased reactive oxygen species (ROS) production, antioxidant treatment inhibited resistin-induced GRP78 expression and impairment of insulin Akt/eNOS signaling, suggesting that ROS may involve resistin-induced ER stress. Resistin also increased JNK phosphorylation, which was prevented by TUDCA. JNK inhibitor SP600125 relieved the resistin inhibitory effects on endothelial insulin Akt/eNOS signaling. In ex vivo experiments, the incubation of aortic rings with resistin impaired insulin- but not acetylcholine-induced vasodilation, which was restored by TUDCA. LNAME (a NOS inhibitor) abolished insulin-induced vasorelaxation in the control or the resistin-treated aortic rings. In addition, resistin increased the mRNA expressions of proinflammatory cytokines tumor nuclear factor (TNF)α and interleukin (IL)-1β, which were also prevented by TUDCA. Conclusion: Our results support the ideal that ER stress may play an important role for resistin impairment of vascular insulin signaling and insulin action. The mitigation of ER stress may represent a new strategy for prevention and treatment of CVDs in obesity and insulin resistant-related diseases.

Basal rot is a common onion disease and is mainly caused by Fusarium oxysporum f. sp. cepae and Fusarium proliferatum. To study the possibility of using volatile organic compounds (VOCs) as biomarkers for these fungi, pathogenic isolates of F. oxysporum and F. proliferatum from onions were cultivated in onion medium and VOCs were measured by solid phase microextraction (SPME). Forty-two compounds were detected, and thirty of these compounds were highly related to fungal metabolic activity. Allyl mercaptan was specific to F. oxysporum isolate Fox006. Analysis of the VOCs showed significant differences between the two species and among different isolates within the same species. Sixteen of the VOCs showed were highly positively correlated with the fungal biomass estimated by real-time polymerase chain reaction (PCR). Ethanol, ethyl formate, ethyl acetate, 2-methyl-1-propanol, methyl thioacetate, n-propyl acetate and 3-methyl-1-butanol are volatile metabolites that were potential indicators of Fusarium growth on onions., (Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

The present study mainly investigates the storm surge variations at different temporal scales using hourly tide gauge data in the Bohai Sea. The seasonal variation, inter-decadal variation, long-term trend and the tide-surge interaction were analyzed separately. The results show that the storm surges in the southwest Bohai Sea are larger than those in the north. The storm surges were more serious in winter (Oct. to Mar.) than in summer half of the year. Significant inter-decadal variations exist in the Bohai Sea, and the extreme storm surge events have been intensifying since 2010. Storm surge intensities at three of the tide gauges (Qinhuangdao, Huludao and Tanggu) exhibited a decreasing trend from 1980 to 2016, with trends significant at the 95% level at Qinhuangdao and Tanggu. Significant tide-surge interactions were observed at all four tide gauges. The tide-surge interaction that results in peak surges mostly occurs during the flood and ebb tides. There is a statistically significant negative correlation between storm surge intensity and the Arctic Oscillation (AO) at Longkou and Tanggu, while there is a significantly positive correlation between storm surge intensity and the Siberian High (SH) at Huludao, Qinhuangdao and Tanggu. A linear regression analysis revealed that the variations of the AO and SH explained 19-48% of the variations in the storm surge intensity in the Bohai Sea.

Ischemia/reperfusion (I/R) is a major cause of acute kidney injury (AKI), along with delayed graft function, which can trigger chronic kidney injury by stimulating epithelial to mesenchymal transition (EMT) in the kidney canaliculus. Sphingosine 1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor that is indispensable for vessel homeostasis. This study aimed to investigate the influence of S1P1 on the mechanisms underlying I/R-induced EMT in the kidney using in vivo and in vitro models. Wild-type (WT) and S1P1-overexpressing kidney canaliculus cells were subject to hypoxic conditions followed by reoxygenation in the presence or absence of FTY720-P, a potent S1P1 agonist. In vivo, bilateral arteria renalis in wild-type mice and mice with silenced S1P1 were clamped for 30 min to obtain I/R models. We found that hypoxia/reoxygenation (H/R) significantly enhanced the expressions of EMT biomarkers and down-regulated S1P1 expression in wild-type canaliculus cells. In contrast, FTY720-P treatment or overexpression of S1P1 significantly suppressed EMT in wild-type canaliculus cells. Furthermore, after 48-72 h, a significant upregulation of EMT biomarker expression was triggered by I/R in mice with silenced S1P1, while the expressions of these markers did not change in wild-type mice. A kt activity was increased with H/R-induced EMT, suggesting that the protective influence of FTY720-P was due to its inhibition of PI3K/Akt. Therefore, the results of this study provide evidence that down-regulation of S1P1 expression is essential for the generation and progression of EMT triggered by I/R. S1P1 exhibits a prominent inhibitory effect on kidney I/R-induced EMT in the kidney by affecting the PI3K/Akt pathway.

Colorectal carcinoma is one of the most common malignancies worldwide and the most prevalent cause of cancer mortality in China. The Miles operation and permanent colostomy are effective treatment. However, these affect the quality of life of patients as they alter normal defecation. Self-efficacy is used to define an individuals' assessments of their ability to perform a specific behavior successfully. It is regarded as an important belief that can predict health behaviors. The aim of this study was to explore the effect of a self-efficacy intervention on the quality of life of patients with a permanent colostomy. Forty-eight patients in treatment for permanent colostomy surgery were divided into the control and intervention groups. The control group received routine nursing; the intervention group was exposed to a 3-month self-efficacy intervention, as well as routine nursing. The two groups completed the Chinese version of a self-efficacy questionnaire at 10 days, 1 month, and 3 months after surgery. Three months after surgery, the two groups also completed a quality-of-life questionnaire. There were significant differences in the quality of life between the two groups. The self-efficacy intervention nursing method improved self-efficacy and the quality of life of patients with intestinal stoma and is worthy of clinical utilization and application.

Monocyte/macrophage recruitment is closely associated with the degree of hypertensive renal injury. We investigated the direct role of macrophages using liposome-encapsulated clodronate (LEC) to deplete monocytes/macrophages in hypertensive renal injury. C57BL/6 mice were treated with a pressor dose of angiotensin (Ang, 1.4 mg/kg/day) II plus LEC or the PBS-liposome for 2 weeks. Ang II mice developed hypertension, albuminuria, glomerulosclerosis, and renal fibrosis. LEC treatment reduced systolic blood pressure (SBP), albuminuria, and protected against renal structural injury in Ang II mice. Ang II significantly increased renal macrophage infiltration (MOMA2 + cells) and the expression of renal tumor necrosis factor α and interleukin β1, which were significantly reduced in Ang II/LEC mice. Ang II increased renal oxidative stress and the expression of profibrotic factors transforming growth factor (TGF) β1 and fibronectin. Ang II also inhibited the phosphorylation of endothelial nitric oxide synthase [phospho-endothelial nitric oxide synthesis (eNOS), ser1177]. LEC treatment reduced renal oxidative stress and TGFβ1 and fibronectin expressions, and increased phospho-eNOS expression in the Ang II mice. In Dahl rats of salt-sensitive hypertension, LEC treatment for 4 weeks significantly attenuated the elevation of SBP induced by high salt intake and protected against renal injury and fibrosis. Our results demonstrate that renal macrophages play a critical role in the development of hypertension and hypertensive renal injury and fibrosis; the underlying mechanisms may be involved in the reduction in macrophage-driven renal inflammation and restoration of the balance between renal oxidative stress and eNOS. Therefore, macrophages should be considered as a potential therapeutic target to reduce the adverse consequences of hypertensive renal diseases.

As a natural agent for chemotherapy, deguelin remarkably suppresses proliferation in numerous solid cancers. Nevertheless, the molecular mechanisms of its suppression are still insufficient. In our research, it was revealed that deguelin induced cell death of lung cancer cells (LCCs) by triggering expression of PUMA. Deguelin triggered PUMA induction independently of p53 via suppression of PI3K/AKT pathway, therefore stimulating Foxo3a to bind with PUMA promoter and stimulate its transcription. Subsequent to activation, PUMA motivated Bax as well as the intrinsic mitochondrial cell death pathway. Removal of PUMA from LCC cells led to deguelin resistance, suggesting deguelin-induced cell death was modulated by PUMA. Furthermore, we demonstrated that deguelin enhanced the chemotherapeutic sensitivity of doxorubicin in vitro and in vivo, which were associated with potentiated PUMA induction. Taken together, these results establish a critical role of PUMA in mediating the anticancer effects of deguelin in lung cancer cells and provide the rationale for clinical evaluation.

Obesity and cigarette smoke are major cardiovascular (CV) risk factors and, when coexisting in the same individuals, have additive/synergistic effects upon CVD. We studied the mechanisms involved in nicotine enhancement of CVD in Sprague Dawley rats with diet-induced obesity. The rats were fed either a high fat (HFD) or normal rat chow diet with or without nicotine (100 mg/L in drinking water) for 20 weeks. HFD rats developed central obesity, increased systolic blood pressure (SBP), aortic superoxide (O2-) production, and impaired endothelial nitric oxide synthase (eNOS) and endothelium-dependent relaxation to acetylcholine (EDR). Nicotine further increased SBP, O2- and impaired eNOS and EDR in obese rats. In the peritoneal macrophages from obese rats, tumor necrosis factor (TNF) α, interleukin 1β and CD36 were increased, and were further increased in nicotine-treated obese rats. Using PCR array we found that 3 of 84 target proinflammatory genes were increased by 2-4 fold in the aorta of obese rats, 11 of the target genes were further increased in nicotine-treated obese rats. HUVECs, incubated with conditioned medium from the peritoneal macrophages of nicotine treated-obese rats, exhibited reduced eNOS and increased NADPH oxidase subunits gp91phox and p22phox expression. Those effects were partially prevented by adding anti-TNFα antibody to the conditioned medium. Our results suggest that nicotine aggravates the CV effects of diet-induced obesity including the oxidative stress, vascular inflammation and endothelial dysfunction. The underlying mechanisms may involve in targeting endothelium by enhancement of macrophage-derived TNFα.

Oxidative stress is considered to be a major contributor to age-related hearing loss (ARHL). Here, we investigated whether pomegranate peel extract (PPE) protected against hearing loss by decreased oxidative stress in the cochlea of D-galactose-induced accelerated aging mice. The aging mice exhibited an increase in hearing threshold shifts and hair cells loss, which were improved in the PPE-treated aging mice. The aging mice also exhibited an increase in 4-hydroxynonenal, the expression of protein phosphatase 1 nuclear targeting subunit (PNUTS), p53 and caspase-3, and a decrease in protein phosphatase 1 (PP1) and MDM2 in the cochlea. PPE treatment reversed the changes in aforementioned molecules. Our results suggested that PPE can protect against ARHL, the underlying mechanisms may involve in the inhibition of oxidative damage of cochlea, possibly by regulating PNUTS/PP1 pathway. The results from the present study provide a new therapeutic strategy to use PPE for prevention of ARHL., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The use of amikacin (AMK) in present treatment strategies results in severe ototoxicity; however, the underlying molecular mechanisms of this toxicity remain unclear. In this study, we investigated the effectiveness of orally administered pomegranate peel extract (PPE), a strong antioxidant, as a protective agent against AMK-induced ototoxicity. To this end, PPE was orally administered to adult BALB/c mice for 5 days, and the mice were then concurrently treated with AMK (500 mg/kg/day for 15 consecutive days). Auditory threshold shifts induced by AMK were significantly attenuated. The results of immunohistochemical staining and western blot analysis revealed that PPE exerted its protective effects by by downregulating the phosphorylation of Forkhead box O3a (FoxO3a), an important transcription factor which is involved in the responses to oxidative stress. The results also showed that PPE treatment inhibited mitogen-activated protein kinase phosphorylation, prevented the activation of pro-apoptotic protein caspase-3, decreased the levels of apoptosis-inducing Bax protein, and increased the levels of the anti-apoptotic mediator, Bcl-2, induced by AMK in the mouse cochlea. Taken together, our experimental findings suggest that phosphorylated FoxO3a mediates AMK-induced apoptosis in BALB/c mice cochlea. PPE effectively attenuated oxidative stress and ototoxicity by regulating FoxO3a, and may thus prove to be beneficial in protecting auditory cells from ototoxic drugs.

The cardioprotective benefits of aldehyde dehydrogenase 2 (ALDH2) are well established, although the regulatory role of ALDH2 in vascular remodeling in pulmonary arterial hypertension (PAH) is largely unknown. ALDH2 potently regulates the metabolism of aldehydes such as 4-hydroxynonenal (4-HNE), the endogenous product of lipid peroxidation. Thus, we hypothesized that ALDH2 ameliorates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting 4-HNE accumulation and regulating downstream signaling pathways, thereby ameliorating pulmonary vascular remodeling. We found that low concentrations of 4-HNE (0.1 and 1μM) stimulated cell proliferation by enhancing cyclin D1 and c-Myc expression in primary HPASMCs. Low 4-HNE concentrations also enhanced cell migration by activating the nuclear factor kappa B (NF-κB) signaling pathway, thereby regulating matrix metalloprotein (MMP)-9 and MMP2 expression in vitro. In vivo, Alda-1, an ALDH2 agonist, significantly stimulated ALDH2 activity, reducing elevated 4-HNE and malondialdehyde levels and right ventricular systolic pressure in a monocrotaline-induced PAH animal model to the level of control animals. Our findings indicate that 4-HNE plays an important role in the abnormal proliferation and migration of HPASMCs, and that ALDH2 activation can attenuate 4-HNE-induced PASMC proliferation and migration, possibly by regulating NF-κB activation, in turn ameliorating vascular remodeling in PAH. This mechanism might reflect a new molecular target for treating PAH., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Low performance of cathode materials has become one of the major obstacles to the application of lithium-ion battery (LIB) in advanced portable electronic devices, hybrid electric vehicles, and electric vehicles. The present work reports a versatile oxygen-deficient LiV 3 O 8 (D-LVO) nanosheet that was synthesized successfully via a facile oxygen-deficient hydrothermal reaction followed by thermal annealing in Ar. When used as a cathode material for LIB, the prepared D-LVO nanosheets display remarkable capacity properties at various current densities (a capacity of 335, 317, 278, 246, 209, 167, and 133 mA h g -1 at 50, 100, 200, 500, 1000, 2000, and 4000 mA g -1 , respectively) and excellent lithium-ion storage stability, maintaining more than 88% of the initial reversible capacity after 200 cycles at 1000 mA g -1 . The outstanding electrochemical properties are believed to arise largely from the introduction of tetravalent V (∼15% V 4+ ) and the attendant oxygen vacancies into LiV 3 O 8 nanosheets, leading to intrinsic electrical conductivity more than 1 order of magnitude higher and lithium-ion diffusion coefficient nearly 2 orders of magnitude higher than those of LiV 3 O 8 without detectable V 4+ (N-LVO) and thus contributing to the easy lithium-ion diffusion, rapid phase transition, and the excellent electrochemical reversibility. Furthermore, the more uniform nanostructure, as well as the larger specific surface area of D-LVO than N-LVO nanosheets may also improve the electrolyte penetration and provide more reaction sites for fast lithium-ion diffusion during the discharge/charge processes.

Puerarin, a major isoflavonoid compound from Chinese herb Kudzu roots, has been widely used for the treatment of hypertensive and cardiovascular diseases in China. Here, we investigated puerarin's beneficial effects on the cardiovascular system in angiotensin (Ang) II-induced hypertensive rats. Sprague-Dawley rats were treated with Ang II for 5 days or with puerarin for 10 days followed by Ang II and puerarin for 5 days. Endothelium-dependent relaxation (EDR) to acetylcholine was determined using an organ chamber bath. Ang II increased the systolic blood pressure (SBP: 178 ± 5 mmHg vs. 112 ± 3 mmHg in control, p < 0.05), aortic (30%, p < 0.05), and left ventricular (LV) weight (23%); puerarin reduced SBP (160 ± 2 mmHg, p < 0.05), aortic, and left ventricular weight in Ang II-infused rats. Puerarin also reduced aortic medial thickness and myocardial cell surface area in Ang II-infused rats. Compared with control rats, Ang II infused rats exhibited an impaired EDR with reduction in the protein expression of phosphor-eNOS at Ser 1177 and an increase in the expression of gp91phox (85%), p22phox (113%), transforming growth factor β1 (145%) and vascular cell adhesion molecule 1 (82%). Puerarin improved EDR and reversed the changes in Ang II-induced protein expression of above molecules. Our results demonstrate that in Ang II-induced hypertensive rats, puerarin protects against endothelial dysfunction and end organ damage with a mild reduction in SBP, and that the cardiovascular beneficial effects of puerarin may be in part attributed to its anti-oxidant and upregulation of phosphor-eNOS.

Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks. An additional group of DS rats was pretreated with puerarin and NS for 10 days, then switched to HS plus puerarin for five weeks. HS for five weeks increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and aortic hypertrophy with increased the expression of phosphor-ERK1/2 in the aorta and heart; puerarin attenuated cardiac and aortic hypertrophy, cardiac fibrosis and phosphor-ERK1/2 with a mild reduction in SBP. Hypertensive rats also manifested impairment of acetylcholine- and insulin-mediated vasorelaxation and insulin-mediated Akt and eNOS phosphorylation associated with the activation of NF[Formula: see text]B/TNF[Formula: see text]/JNK pathway. Puerarin improved acetylcholine- and insulin-mediated vasorelaxation and insulin-stimulated Akt/NO signaling with the inhibition of the NF[Formula: see text]B inflammatory pathway. Our results demonstrated that in salt-sensitive hypertension, puerarin improved vascular insulin action with cardiovascular beneficial effects. Our results found that the underlying mechanisms may involve its inhibition of NF[Formula: see text]B/JNK and ERK1/2 pathway. These results suggest that puerarin could be used as a new antihypertensive agent to expand our armamentarium for the prevention and treatment of end-organ damage in individuals with hypertension and metabolic diseases.

Objectives: This study sought to examine the level of health-related knowledge and its predictors among vocational college students in China., Study Design: A cross-sectional study., Methods: A survey was performed to collect data on heath-related knowledge and potential risk factors among 708 students in four higher vocational colleges at Nanyang, Henan, China. Linear regression models were conducted to identify the predictors of the level of health-related knowledge., Results: The level of health-related knowledge among Chinese vocational college students is extremely low (only 1.4% students have an adequate level of health-related knowledge). According to the multivariate analysis, major, year of class, place of origin and a mother's education level are significantly associated with health-related knowledge in Chinese vocational college students., Conclusions: Health education and health promotion efforts are encouraged to improve the level of health-related knowledge in this population. Attention and efforts to improve health-related knowledge of Chinese vocational college students who come from rural areas, whose mothers have a lower level of education, who are in non-medicine majors and during the first few years of vocational college is warranted., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We extracted and purified d-galactose-6-sulfurylase from Betaphycus gelatinus by ammonium sulfate precipitation, ion exchange chromatography and hydrophobic interaction chromatography and investigated the desulfation of carrageenan by the purified enzyme. The purity of the enzyme increased 4.9 fold with approximately 3.7% yield of the crude extract. It was able to catalyze the conversion of μ- to κ-carrageenan. The purified enzyme was a monomeric protein with a molecular weight at about 65 kDa. The maximum activity of the enzyme was observed at pH 7.0 and temperature 40 °C. 26% of the total sulfate was removed from the carrageenan when treated with 18 U purified enzyme. The conversion from μ- to κ-carrageenan was confirmed through the IR spectral analysis of both the control and enzyme treated carrageenan. This study proved that there is a congeneric enzyme that has the same mechanism with alkali treatment on carrageenan from a new kind of red algae Betaphycus gelatinus, which is an alternative way of alkali treatment to the production of carrageenan. The existence of precursor μ-carrageenan in Betaphycus gelatinus was evidently found in this study., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: The clinical use of aminoglycoside antibiotics is limited in most countries because of auditory toxicity side effects. However, their use is common in developing countries because they are inexpensive and convenient. Salvia miltiorrhiza extracts are used clinically in China for their antioxidant properties. We investigated the effect of a clinically approved injectable S. miltiorrhiza solution on inducible nitric oxide synthase (iNOS) generation induced by the aminoglycoside antibiotic gentamicin and an ototoxicity protective mechanism., Methods: Sixty adult guinea pigs were used in this study and divided into four groups. Auditory brainstem response (ABR) testing was performed before and after treatments and animals were sacrificed for morphological and immunostaining assays after determining threshold shifts in ABR. The cochleae were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to observe ultrastructural changes. In addition, hair cell loss, iNOS and caspase-3 expression, and apoptosis were measured., Results: The result showed that hearing loss, iNOS overexpression accompanied with disorganization in the cochlea, and terminal deoxynucleotidyl transferase- mediated dUTP- biotin nick end labeling (TUNEL)-stained positive cells in animals treated with gentamicin. However, pretreatment with S. miltiorrhiza (3g/kg/day for 10 days) decreased gentamicin-induced hearing loss, attenuated iNOS and caspase-3 expression, and decreased the number of apoptotic cells. Furthermore, it also reduced the ultrastructural damage due to ototoxicity as observed by SEM and TEM., Conclusions: These findings indicate that S. miltiorrhiza protects against gentamicin-induced ototoxicity and could apply to the protection of ototoxicity., (© 2014.)

Insulin resistance and hypertension are considered as prototypical "diseases of civilization" that are manifested in the modern environment as plentiful food and sedentary life. The human propensity for insulin resistance and hypertension is a product, at least in part, of our evolutionary history. Adaptation to ancient lifestyle characterized by a low sodium, low-calorie food supply and physical stress to injury response has driven our evolution to shape and preserve a thrifty genotype, which is favorite with energy-saving and sodium conservation. As our civilization evolved, a sedentary lifestyle and sodium- and energy-rich diet, the thrifty genotype is no longer advantageous, and may be maladaptive to disease phenotype, such as hypertension, obesity and insulin resistance syndrome. This article reviews human evolution and the impact of the modern environment on hypertension and insulin resistance.

Scorpion venoms metalloproteinase is involved in a number of important biological, physiological and pathophysiological processes. In this work, a complete sequence of metalloproteinase was first obtained from venom of scorpion Buthus martensi and named as BumaMPs1. BumaMPs1 has 393 amino acid residues containing with a molecular mass of 44.53 kDa, showing an isoelectric point of 5.66. The primary sequence analysis indicated that the BumaMPs1 contains a zinc-binding motif (HELGHNLGISH), methionine-turn motif (YIM), disintegrin-like domain (ETCD) and N-glycosylation site. The multiple alignment of its deduced amino acid sequence and those of other metalloproteinase showed a high structural similarly, mainly among class reprolysin proteases. The phylogenetic analysis showed early divergence and independent evolution of BumaMPs1 from other metalloproteinase., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Ototoxic drug-induced apoptosis of inner ear cells has been shown to be associated with calpain expression. Cisplatin has severe ototoxicity, and can induce cochlear cell apoptosis. This study assumed that cisplatin activated calpain expression in apoptotic cochlear cells. A mouse model of cisplatin-induced ototoxicity was established by intraperitoneal injection with cisplatin (2.5, 3.5, 4.5, 5.5 mg/kg). Immunofluorescence staining, image analysis and western blotting were used to detect the expression of calpain 1 and calpain 2 in the mouse cochlea. At the same time, the auditory brainstem response was measured to observe the change in hearing. Results revealed that after intraperitoneal injection with cisplatin for 5 days, the auditory brainstem response threshold shifts increased in mice. Calpain 1 and calpain 2 expression significantly increased in outer hair cells, the spiral ganglion and stria vascularis. Calpain 2 protein expression markedly increased with an increased dose of cisplatin. Results suggested that calpain 1 and calpain 2 mediated cisplatin-induced ototoxicity in BALB/c mice. During this process, calpain 2 plays a leading role.

D-Gal-6-sulfurylase catalyzing the conversion of μ-carrageenan into κ-carrageenan was extracted from Eucheuma striatum and purified by ammonium sulfate precipitation, hydrophobic interaction chromatography and ion exchange chromatography. The purified enzyme was a monomeric protein with a molecular mass of about 65 kDa as shown in SDS-PAGE. The maximum activity of the enzyme was observed at pH 7.0 and temperature 40°C. Km value for μ-carrageenan was 4.31 mM, and the corresponding Vmax was 0.17 mM min(-1). The carrageenan treated with 10 U of the purified enzyme exhibited 7.1-fold increase in gel strength with a removal of 30% sulfate groups. (1)H NMR spectral analysis of the control and enzyme treated carrageenan confirmed the conversion of μ- into κ-carrageenan and highlighted the specificity of Gal-6-sulfurylase for μ-carrageenan. This Gal-6-sulfurylase provides an eco-friendly and alternative for alkali treatment method to produce high gel strength κ-carrageenan., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. Alpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase.