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Showing papers in "BioScience Trends in 2018"


Journal ArticleDOI
TL;DR: Some Chinese herbal medicines have a significant effect on reducing cancer-related fatigue and pain, improving peripheral neuropathy and gastrointestinal side effects including diarrhea, nausea, and vomiting, decrease the incidence of bone marrow suppression, and protecting anthracycline-induced cardiotoxicity and radiation-induced pneumonitis.
Abstract: Numerous studies have indicated that in cancer treatment Chinese herbal medicines in combination with chemo-, radio-, or targeted-therapy can be used to enhance the efficacy of and diminish the side effects and complications caused by these therapies. Therefore, an understanding of Chinese herbal medicines is needed by physicians and other health care providers. This review provides an update on Chinese herbal medicines as adjuvant treatment of anticancer therapeutics. First, some Chinese herbal medicines (e.g. Astragalus, Ginseng, Scutellaria barbata, TJ-41, TJ-48, PHY906, Huachansu injection, and Kanglaite injection) that are commonly used for treating the cancer and/or reducing the toxicity induced by chemo-, radio-, or targeted-therapy are discussed. These Chinese herbal medicines have been shown to possess great advantages in terms of suppressing tumor progression, increasing the sensitivity of chemo-, radio-, or targeted-therapeutics, improving an organism's immune system function, and lessening the damage caused by these therapeutics. Second, some clinical trials using Chinese herbal medicines as adjuvant improving cancer treatment related side effects and complications are reviewed. Some Chinese herbal medicines have a significant effect on reducing cancer-related fatigue and pain, improving peripheral neuropathy and gastrointestinal side effects including diarrhea, nausea, and vomiting, decrease the incidence of bone marrow suppression, protecting anthracycline-induced cardiotoxicity and radiation-induced pneumonitis, and relieving EGFR-TKIs related acneiform eruptions and other side effects. This review of those medicines should contribute to an understanding of Chinese herbal medicines as adjuvant treatment for cancer and provide useful information for the development of more effective anti-cancer drugs. However, rigorously designed trials on potential Chinese herbal medicine must be further examined involving cancer treatment especially molecular targeted-therapy in the future.

151 citations


Journal ArticleDOI
Chenzhong Wang1, Yi Yang1, Yueqi Zhang1, Jinyu Liu1, Zhenjun Yao1, Chi Zhang1 
TL;DR: Evidence is provided that metformin suppresses IL-1β-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metform in's potential in prevention and treatment of osteOarthritic joint disease.
Abstract: Mitochondrial damage is involved in the pathogenesis of osteoarthritis. Metformin, one of the most common prescriptions for patients with type 2 diabetes, can reportedly activate Sirtuin 3 (SIRT3) expression which protects mitochondria from oxidative stress. In this study, we investigated the inhibitory property of metformin on mitochondrial damage by focusing on the interleukin-1 beta (IL-1β)-stimulated osteoarthritis model by using primary murine chondrocytes. Our results demonstrated that SIRT3 was downregulated in chondrocytes under IL-1β stimulation, where its expression was positively correlated with mitochondrial damage and reactive oxygen species (ROS) production. Metformin treatment upregulated SIRT3 expression and mitigated loss of cell viability and decreased the generation of mitochondria-induced ROS in chondrocytes stimulated with IL-1β. Metformin also attenuated IL-1β-induced expressions of catabolic genes such as matrix metalloproteinase-3 (MMP3) and MMP13 and enhanced the anabolic indicator Collagen Ⅱ. These effects were mediated by phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1)/Parkin-dependent mitophagy and the autophagic elimination of damaged mitochondria. Further, the SIRT3 inhibitor 3-TYP effectively inhibited the initiation of mitophagy, as decreased expression of PINK1 and Parkin, decreased the LC3II/LC3I, enhanced the expression of MMP3 and MMP13, and decreased the expression of Collagen Ⅱ. Overall, our findings provide evidence that metformin suppresses IL-1β-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin's potential in prevention and treatment of osteoarthritic joint disease.

87 citations


Journal ArticleDOI
TL;DR: Investigation of the pattern of immune cells and related functional molecules in peripheral blood and at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion found peripheral Treg cells did not increase in pregnant women with URSA.
Abstract: The aim of the current study was to determine the pattern of immune cells and related functional molecules in peripheral blood and at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion (URSA). In part I, 155 women were included and divided into four groups: non-pregnant controls with no history of URSA (NPCs), pregnant controls with no history of URSA (PCs), non-pregnant women with a history of URSA (NPUs), and pregnant women with a history of URSA (PUs). Venous blood samples were collected and analyzed. In part II, 35 subjects with URSA and 40 subjects in the early stage of normal pregnancy who chose to undergo an abortion were recruited. Samples of the decidua were collected, and the proportion of immune cells and the expression of related molecules were evaluated. Peripheral regulatory T cells (Treg cells) increased in PCs compared to NPCs, but in women with URSA the flux of Treg cells disappeared when pregnancy occurred. Levels of interleukin-10 (IL-10), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and IL-17 and the ratio of Th17/Treg cells in peripheral blood remained stable among the four groups. At the maternal-fetal interface, the percentage of Treg cells, the level of CTLA-4 of CD4+CD25+CD127lo cells and CD4+Foxp3+ cells were significantly lower in women with URSA compared to controls, respectively. Levels of transforming growth factor-β1 (TGF-β1) mRNA and protein in the decidua significantly decreased in URSA while levels of IL-6 and tumor necrosis factor-ɑ (TNF-ɑ) and the Th17/Treg ratio significantly increased. In conclusion, peripheral Treg cells did not increase in pregnant women with URSA. The decrease in Treg cells and levels of CTLA-4 and TGF-β1 and as well as the increase in levels of IL-6 and TNF-ɑ, and the Th17/Treg ratio at the maternal-fetal interface might contribute to inappropriate maternal-fetal immune tolerance in URSA.

74 citations


Journal ArticleDOI
TL;DR: To further reduce the disparity in the medical economic burden and to increase the overall protection from financial risk in China, the Government should increase central government transfers to NCMS and URBMI enrollees in poor regions and increase the total amount of government subsidies toNCMS.
Abstract: The aims of this study were to describe health insurance reforms initiated by the Chinese government over the past two decades, to review their achievements in reducing the medical economic burden, and to summarize the challenges that still exist regarding a further reduction in out-of-pocket expenditures in this country. China has successfully attained the goal of providing health insurance coverage to almost the entire population by developing a mixed health insurance system, which consists of Urban Employees Basic Medical Insurance (UEBMI), Urban Resident Basic Medical Insurance (URBMI), New Rural Cooperative Medical Scheme (NCMS), and supplementary Catastrophic Health Insurance. Despite this achievement, China is still facing the challenges of a disparity in the medical economic burden by region and by health insurance scheme, relatively little protection from financial risk compared to developed countries, as well as low efficiency and quality of care under current payment systems. To further reduce the disparity in the medical economic burden and to increase the overall protection from financial risk in China, the Government should increase central government transfers to NCMS and URBMI enrollees in poor regions and increase the total amount of government subsidies to NCMS. In addition, China should improve the efficiency and quality of health insurance by further reforming the payment system.

41 citations


Journal ArticleDOI
TL;DR: The financial aspects of the medical care and welfare services policy for the elderly in Japan are introduced and other aging countries could learn from the Japanese experience of solving barriers to healthcare policy forThe elderly.
Abstract: Elderly care is an emerging global issue threatening both developed and developing countries. The elderly in Japan increased to 26.7% of the population in 2015, and Japan is classified as a super-aged society. In this article, we introduce the financial aspects of the medical care and welfare services policy for the elderly in Japan. Japan's universal health insurance coverage system has been in place since 1961. Long-term care includes welfare services, which were separated from the medical care insurance scheme in 2000 when Japan was already recognized as an aging society. Since then, the percentage of the population over 65 has increased dramatically, with the productive-age population on the decrease. The Japanese government, therefore, is seeking to implement "The Community-based Integrated Care System" with the aim of building comprehensive up-to-the-end-of-life support services in each community. The system has four proposed elements: self-help (Ji-jo), mutual aid (Go-jo), social solidarity care (Kyo-jo), and government care (Ko-jo). From the financial perspective, as the government struggles against the financial burdens of an aging population, they are considering self-help and mutual aid. Based on Japan's present situation, both elements could lead to positive results. The Japanese government must also entrust the responsibility for implementing preventive support to municipalities through strongly required regional autonomy. As Japan has resolved this new challenge through several discussions over a long period of time, other aging countries could learn from the Japanese experience of solving barriers to healthcare policy for the elderly.

39 citations


Journal ArticleDOI
TL;DR: OCT and laser ablation-based theranostics can give more precision and intelligence for intraoperative diagnosis and therapeutics in clinical applications and can precisely locate, or specifically target cancerous tissues, and then as much as possiblly eliminate them.
Abstract: This review focuses on optical coherence tomography (OCT)-based neurosurgical application for imaging and treatment of brain tumors. OCT has emerged as one of the most innovative and successful translational biomedical-diagnostic techniques. It is a useful imaging tool for noninvasive, in vivo, in situ and real-time imaging in soft biological tissues, such as brain tumor imaging. OCT can detect the structure of biological tissue in a micrometer scale, and functional OCT has some clinical researches and applications, such as nerve fiber tracts and neurovascular imaging. OCT is able to identify tumor margins, and it gives intraoperative precision identification and resection guidance. OCT-based theranostics is introduced into preclinical neurosurgical resection, such as the integration of OCT and laser ablation. We discuss the challenges and opportunities of OCT-based system in the field of combination of intraoperative structural and functional imaging, neurosurgical guidance and minimally invasive theranostics. We point out that OCT and laser ablation-based theranostics can give more precision and intelligence for intraoperative diagnosis and therapeutics in clinical applications. The theranostics can precisely locate, or specifically target cancerous tissues, and then as much as possiblly eliminate them.

35 citations


Journal ArticleDOI
TL;DR: Results from multivariate quantitative models showed that the regional differences of population aging appear to be affected much more by the large-scale internal migration with clear age selectivity and orientation preference than by the impact of fertility and mortality.
Abstract: In addition to birth and death, migration is also an important factor that determines the level of population aging in different regions, especially under the current context of low fertility and low mortality in China. Drawing upon data from the fifth and sixth national population census of 287 prefecture-level cities in China, this study explored the spatial patterns of population aging and its trends from 2000 to 2010 in China. We further examined how the large-scale internal migration was related to the spatial differences and the changes of aging by using multivariate quantitative models. Findings showed that the percentage of elder cities (i.e. proportion of individuals aged 65 and above to total population is higher than 7%) increased from 50% to 90% in the total 287 cities within the decade. We also found that regional imbalances of population aging have changed since 2000 in China. The gap of aging level between East zone and the other three zones (i.e. West, Central, and North-east) has considerably narrowed down. In 2000, Eastern region had the greatest number (65) of and the largest proportion (74.7%) of elder cities among all four regions. By 2010, the proportion (87.4%) of elder cities in the eastern region was slightly lower than Central (91.4%), Western (88.2%) and North-east sectors (91.2%). Results from multivariate quantitative models showed that the regional differences of population aging appear to be affected much more by the large-scale internal migration with clear age selectivity and orientation preference than by the impact of fertility and mortality. Population aging is expected to continue in China, which will in turn exacerbate regional imbalances. Policies and implications are discussed to face the challenges that the divergent aging population may present in China.

31 citations


Journal ArticleDOI
TL;DR: Investigating the protective effect of Paeoniflorin and the role of the Janus kinase (JAK) 2/signal transducer (STAT) 3 signaling pathway on diabetic nephropathy revealed protective effects may be associated with the prevention of macrophage infiltration and inhibition of the JAK2/STAT3 signaling pathway.
Abstract: Paeoniflorin is the main bioactive components of the root of P.lactiflora Pall., and has been widely used as an anti-inflammation and immunomodulatory agent. However, the effect and mechanisms of Paeoniflorin in diabetic nephropathy (DN) remains to be elucidated. In the present study, streptozotocin (STZ)-induced type 1 diabetic mice model was used to investigate the protective effect of Paeoniflorin and the role of the Janus kinase (JAK) 2/signal transducer (STAT) 3 signaling pathway on DN. After treatment with Paeoniflorin at a dose of 25, 50 and 100 mg/kg once a day for 12 weeks, both the functional and histological damage to diabetic mice kidney had been attenuated significantly. Additionally, these reno-protective effects were associated with alleviating macrophage infiltration and inflammatory factors expression as well as suppression of the JAK2/STAT3 signaling pathway. These data reveal that Paeoniflorin attenuates renal lesions in diabetic mice and these protective effects may be associated with the prevention of macrophage infiltration and inhibition of the JAK2/STAT3 signaling pathway.

28 citations


Journal ArticleDOI
TL;DR: The diagnosis-related group (DRG)-based case-mix payment system, with its superior efficiency and containment of costs, has garnered increased attention and it represents a promising alternative to the prevailing method of payment in most Chinese public hospitals.
Abstract: Fee for services (FFS) is the prevailing method of payment in most Chinese public hospitals. Under this retrospective payment system, medical care providers are paid based on medical services and tend to over-treat to maximize their income, thereby contributing to rising medical costs and uncontrollable health expenditures to a large extent. Payment reform needs to be promptly implemented to move to a prospective payment plan. The diagnosis-related group (DRG)-based case-mix payment system, with its superior efficiency and containment of costs, has garnered increased attention and it represents a promising alternative. This article briefly describes the DRG-based case-mix payment system, it comparatively analyzes differences between FFS and case-mix funding systems, and it describes the implementation of DRGs in China. China's social and economic conditions differ across regions, so establishment of a national payment standard will take time and involve difficulties. No single method of provider payment is perfect. Measures to monitor and minimize the negative ethical implications and unintended effects of a DRG-based case-mix payment system are essential to ensuring the lasting social benefits of payment reform in Chinese public hospitals.

28 citations


Journal ArticleDOI
TL;DR: The excellent in vitro efficacy and specificity of an adaptor-controlled CAR-T therapy to target both tumor cells and tumor-associated macrophages in NSCLCs were validated.
Abstract: Our goal is to develop a switch-controlled approach to enable better control of reactivity and safety of chimeric antigen receptor (CAR)-T therapy for non-small-cell lung cancer (NSCLC). Lentiviral transduction was performed to generate anti-FITC CAR-T cells and target cells stably expressing either isoform of the folate receptor. Colorimetric-based cytotoxic assay, enzyme-linked immunosorbent assay, and multiparametric flow cytometry analysis were used to evaluate the specificity and activity of CAR-T cells in vitro. Human primary T cells stably expressing the fully human anti-FITC CAR were generated. Anti-FITC CAR-T cells displayed antigen-specific and folate-FTIC dependent reactivity against engineered A549-FRα and THP-1-FRβ. The selective activation and proliferation of anti-FITC CAR-T cells in vitro stringently relied on the co-existence of folate-FITC and FR- expressing target cells and was dose-titratable with the folate-FITC switch. The excellent in vitro efficacy and specificity of an adaptor-controlled CAR-T therapy to target both tumor cells and tumor-associated macrophages in NSCLCs were validated.

28 citations


Journal ArticleDOI
TL;DR: How the field of HTA has developed in China is reviewed, what factors have been influencing China's HTA development, and policy recommendations are proposed.
Abstract: Health technology assessment (HTA) is a field of scientific policy research that adopts multidisciplinary approaches to conduct systematic evaluation of health technologies and inform decision making. Although achievements have been made by HTA activities among academics, providers, and policy makers, development of the field of HTA in China is fragmented and not yet formally integrated in health policy making processes. All stakeholders need to make more efforts to strengthen HTA knowledge translation and facilitate a decision making process that is based on evidence including HTA findings. This article reviews how the field of HTA has developed in China, analyzes what factors have been influencing China's HTA development, and proposes policy recommendations.

Journal ArticleDOI
Chuanqi Zhang1, Min Wang1, Cong Shi1, Fanli Shi1, Cheng Pei1 
TL;DR: Linc00312 enhanced the sensitivity of SKOV3/DDP cells to cisplatin by promoting cell apoptosis via the Bcl-2/Caspase-3 signaling pathway, and may be a promising clinical strategy for the treatment of drug-resistant OC.
Abstract: Chemotherapy is one of the main treatments for ovarian cancer (OC). Cisplatin combined with paclitaxel is a commonly used chemotherapy regimen. However, effective cancer therapy is hindered by a patient's resistance to cisplatin. The mechanism that potentially leads to that resistance is unclear. The current study examined the mechanism by which Linc00312 is involved in resistance to cisplatin in OC. Quantitative real-time PCR (RT-qPCR) was used to test for expression of Linc00312 in freshly frozen tissue samples of OC and in SKOV3 and SKOV3/DDP cells. In situ hybridization was performed to examine the distribution of Linc00312 expression in paraffin-embedded histological sections that were sensitive or resistant to cisplatin. The cell counting kit-8 assay was used to detect cell viability. Flow cytometry was used to measure cell apoptosis. RT-qPCR was performed to confirm changes in expression of MDR1, MRP1, Bcl-2, Bax, Caspase-3, and Caspase-9 mRNA. Levels of MDR1, Bcl-2, Bax, Caspase-3, and Caspase-9 protein were detected with Western blotting. Experiments indicated that the expression of Linc00312 decreased significantly in SKOV3/DDP cells compared to that in SKOV3 cells. Upregulation of Linc00312 can considerably increase the sensitivity of SKOV3/DDP cells to cisplatin, while down-regulation of Linc00312 has the exact opposite effect in SKOV3 cells. Linc00312 enhanced the sensitivity of SKOV3/DDP cells to cisplatin by promoting cell apoptosis via the Bcl-2/Caspase-3 signaling pathway. These findings suggest that Linc00312 may be a promising clinical strategy for the treatment of drug-resistant OC.

Journal ArticleDOI
TL;DR: It is shown that APS can promote proliferation and decrease apoptosis in AGE-induced DCM cell model, besides, APs can decrease intracellular ROS level, increase activity of SOD, GSH-Px and lower level of MDA and NO in DCM model cells, indicating APS exerted antioxidative function in DCm model cells.
Abstract: Diabetic cardiomyopathy (DCM) is one of the main cardiac complications among diabetic patients. According to previous studies, the pathogenesis of DCM is associated with oxidative stress, apoptosis and proliferation of local cardiac cells. It showed, NRG1 can improve the function of mitochondria, and thereby, increasing proliferation and decreasing apoptosis of cardiac muscle cell via ErbB/AKT signaling, also, exert antioxidative function. Besides, NRG1/ErbB pathway was impaired in the DCM model which suggested this signaling played key role in DCM. Astraglaus polysaccharide (APS), one of the active components of Astragalus mongholicus, showed striking antioxidative effect. Here, in this study, our data showed that APS can promote proliferation and decrease apoptosis in AGE-induced DCM cell model, besides, APS can decrease intracellular ROS level, increase activity of SOD, GSH-Px and lower level of MDA and NO in DCM cell model, indicating APS exerted antioxidative function in DCM model cells. Besides, western blot results revealed APS induced NRG1 expressing and the phosphorylation level of ErbB2/4. In addition, the elevated NRG1 promoted AKT and PI3k phosphorylation which indicated APS may exert its function by NRG1/ErbB and the downstream AKT/PI3K signaling. Canertinib is ErbB inhibitor. The effect of APS on proliferation, apoptosis, antioxidation and NRG1/ErbB pathway was partly abolished after the cells were co-treated with APS and canertinib. Taken together, these results suggested APS may display its protective function in DCM cells by activating NGR1/ErbB signaling pathway. And our study increased potential for prevention and therapy to DCM.

Journal ArticleDOI
TL;DR: Comparable results were demonstrated between the two groups, while the robotic system seemed to shorten the learning curve of minimally invasive pancreaticoduodenectomy (PD); however, these results did not reach statistical significance.
Abstract: In this study, the clinical effectiveness of the robot-assisted laparoscopic pancreatico-duodenectomy (RPD) and Total laparoscopic pancreaticoduodenectomy LPD were retrospectively reviewed. From December 2013 to September 2017, 20 patients underwent robot-assisted laparoscopic pancreaticoduodenectomy and 80 patients underwent Total laparoscopic pancreaticoduodenectomy. The clinical data of the RPDs and the first 20 LPDs were reviewed retrospectively. There is no difference in operative time, estimated blood loss, length of stay, and rates of complications and mortality between the LPD and RPD group. The next 10 cases in the RPD group had shorter operative times (p = 0.03) than the first 10 cases. The estimated blood loss and length of stay were also lower in the next 10 cases; however, these results did not reach statistical significance. Our results show that LPD and RPD are technically safe and feasible. Comparable results were demonstrated between the two groups, while the robotic system seemed to shorten the learning curve of minimally invasive pancreaticoduodenectomy (PD).

Journal ArticleDOI
TL;DR: The current results suggest that crocin alleviates obesity in db/db mice and that it inhibits adipocyte differentiation in preadipocytes and inhibits lipolysis via activation of AMPK.
Abstract: Obesity has become a severe public health problem worldwide. Crocin, a natural product, has been reported to have a number of pharmacological activities, including anti-inflammatory, anti-cancer, neuroprotective, antihypertensive, and cardioprotective action. The aims of the current study were to identify the beneficial effects of crocin on obesity, adipocyte differentiation, and lipolysis and to evaluate the possible role of AMPK. Results indicated that crocin significantly increased AMPK phosphorylation in differentiated adipocytes in vitro and in adipose tissue in db/db mice. Crocin reduced lipid accumulation in differentiated adipocytes. In addition, crocin inhibited the expression of mRNA of important adipogenesis-related regulators, including CEBPα, CEBPβ, PPARγ, aP2, FAS, and CD36, in both differentiated adipocytes and adipose tissue in db/db mice. Crocin increased the expression of mRNA of key lipolysis-associated factors, including PPARα, LPL, and HSL, in both differentiated adipocytes and adipose tissue in db/db mice. In adipocytes, knockdown of AMPK significantly suppressed the crocin-induced inhibition of adipocyte differentiation and increase in lipolysis. BML-275 is an inhibitor of AMPK. In adipose tissue in db/db mice, BML-275 suppressed crocin-induced inhibition of fat formation and alleviation of a metabolic disorder. The current results suggest that crocin alleviates obesity in db/db mice and that it inhibits adipocyte differentiation in preadipocytes. Crocin inhibits adipogenesis and promotes lipolysis via activation of AMPK. Therefore, crocin may have promise as an option for the clinical treatment for obesity and associated metabolic diseases.

Journal ArticleDOI
TL;DR: A reliable and easy-to-use prediction score to predict the risk of HE in ICH is devised and the grading system demonstrated acceptable accuracy in an independent single-institution study.
Abstract: Hematoma expansion (HE) is an independent predictor of poor outcome and secondary neurological deterioration in intracerebral hemorrhage (ICH) and is associated with high morbidity and mortality. Noncontrast computed tomography (NCCT) may identify the sites of active extravasation. Therefore, we have attempted to (1) devise a reliable and easy-to-use prediction score to predict the risk of HE in ICH and (2) validate the accuracy of this grading system and perform an independent analysis of HE predictors. We included patients in whom an intracerebral hemorrhage (ICH) occurred in the basal ganglia between Jan. 2015 and Jan. 2018. These patients had undergone a baseline CT scan at Qinghai Provincial People's Hospital within 24 hours after the onset of ICH symptoms. Two observers independently assessed the presence of the island sign, blend sign, or swirl sign on an NCCT scan during patient selection. Patients underwent a baseline NCCT scan and 24-hour NCCT follow-up for analysis of HE. The accuracy of this grading system was assessed. Independent predictors of HE were identified using multivariable regression. Of 266 patients with ICH, 61 (22.93%) presented with the island sign, 63 (23.68%) presented with the blend sign, and 50 (18.80%) presented with the swirl sign. The overall incidence of HE was 37.22% (99/266). Of 125 patients (46.99%) who underwent a baseline CT scan within 6 hours of onset, 141 (53.01%) underwent a scan in 6-24 hours. Multivariable logistic regression analysis identified the hematoma volume (OR, 0.974; P = 0.042), intraventricular hemorrhage (IVH) extension (OR, 3.225; P = 0.003), time from onset to the baseline CT scan (OR, 0.986; P 1.5 (OR, 3.362; P = 0.006) as closely associated with HE. In conclusion, the grading system demonstrated reliable accuracy at predicting HE. The grading system demonstrated acceptable accuracy in an independent single-institution study. The role of the grading system in predicting HE and poor outcome in patients with ICH is significant. NCCT imaging markers may serve as key markers for HE prediction.

Journal ArticleDOI
Zhipeng Sun1, Yubing Zhu1, Aminbuhe1, Qing Fan1, Jirun Peng1, Nengwei Zhang1 
TL;DR: APE1 demonstrates cancer progression potential at the clinical, tissue and cell level and provides a new idea and theoretical basis for APE1-based clinical diagnosis, prognosis determination and molecular targeted therapy in treatment of HCC.
Abstract: This research aimed to investigate the differential expression of apurinic-apyrimidinic endonuclease 1 (APE1) in hepatocellular carcinoma (HCC) tissues and cells and the effects on proliferation and apoptosis of cancer cells. Immunohistochemical techniques were used to detect the expression of APE1 in 80 cases of HCC and the corresponding paracancerous tissue microarrays; meanwhile, Western blots were used to detect the expression of APE1 in both human HCC BEL-7402, BEL-7405, HCC-9204, Hep3B, HepG2, SMMC-7721 and Huh-7 cells, and normal hepatocyte L-02 cells. The relationship between APE1 expression and clinical pathological characteristics of HCC was statistically analyzed. APE1 shRNA vector was constructed in Hep 3B cells to establish a stably transfected cell line, using Western blots to determine the interference efficiency. Cell proliferation activity was detected with MTT assays, while apoptosis was detected with the Annexin V-FITC/PI double-labeling technique. The expression of APE1 in HCC tissues and cells was significantly up-regulated, and its expression was significantly different from TNM staging and histopathological grading. Down-regulation of APE1 expression significantly reduced the proliferative activity and increased the apoptosis rate of Hep 3B cells. In conclusion, APE1 demonstrates cancer progression potential at the clinical, tissue and cell level. It provides a new idea and theoretical basis for APE1-based clinical diagnosis, prognosis determination and molecular targeted therapy in treatment of HCC.

Journal ArticleDOI
Xiaoyong Lan1, Haiping Ma1, Zhiping Zhang1, Dong Ye1, Jun Min1, Feng Cai1, Jun Luo1 
TL;DR: It was observed that TUG1 expression level was significantly lower in ankylosing spondylitis patients than in healthy controls in both serum and biopsies, and downregulation of lncRNA Tug1 is related to higher disease activity, longer course of treatment and higher rehospitalization rate.
Abstract: Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) promotes osteosarcoma, while its involvement in other bone diseases, such as ankylosing spondylitis (AS) is unknown. Expression of TUG1 in serum and open sacroiliac biopsies of AS patents and healthy controls was detected by real-time quantitative PCR (qRT-PCR). Ankylosing spondylitis disease activity score (ASDAS) system was used to evaluate disease activity. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of lncRNA TUG1 for AS. Chi-square test was performed to analyze the correlations between TUG1 expression and patients' clinicopathological data. Patients were divided into 2 groups (high and low expression groups) according to the median expression level of TUG1 and were followed-up for 5 years after discharge. Treatment courses and rehospitalization rate were compared between two groups. It was observed that TUG1 expression level was significantly lower in AS patients than in healthy controls in both serum and biopsies. Reduced expression level of TUG1 distinguished AS patients from controls. LncRNA TUG1 expression was significantly correlated with patients' smoking habits, disease activity, and course of disease. Patients in high expression group showed longer hospitalization time and higher rehospitalization rate. We therefore conclude that expression of lncRNA TUG1 was inhibited in AS patients and downregulation of lncRNA TUG1 is related to higher disease activity, longer course of treatment and higher rehospitalization rate.

Journal ArticleDOI
TL;DR: The ability of DJC to ameliorate diabetic renal dysfunction and the associated pathologies of this disease might be due to its antioxidant capacity and suppression of the JAK2-STAT1/STAT3 cascade.
Abstract: Danzhi Jiangtang Capsule (DJC), a traditional Chinese medicinal formula, has been used clinically in treating diabetes and diabetic nephropathy (DN). We previously demonstrated that DJC is capable of improving renal function in patients and rats with DN, but the mechanisms underlying these therapeutic benefits of DJC are not quite clear yet. In this study, STZ-induced diabetic rats were orally administered DJC for 8 weeks. Fasting blood glucose, renal function indicators in the serum, renal index, and the expression of proteins related to JAK-STAT signaling pathway were evaluated at the end of the experiment. The kidneys were sliced for pathological histology. Antioxidant status was assessed by measuring SOD, LPO and MDA in serum. The expression levels of COX2, iNOS, SOCS and the phosphorylation status of JAK2, STAT1, and STAT3 in renal tissues were evaluated by Western blot analyses. IL-6, TNF-α, and MCP-1 expression levels in renal tissues were determined using double-antibody sandwich ELISA. Diabetic renal dysfunction and its associated pathologies were ameliorated by DJC treatment. DJC significantly reversed the high expression of COX2 and iNOS in renal tissues. Furthermore, DJC inhibited the JAK2-STAT1/STAT3-SOCS3 signaling pathway, resulting in decreased concentrations of IL-6, TNF-α, and MCP-1. Moreover, the oxidant status in the kidney was substantially ameliorated by DJC treatment. In conclusion, the ability of DJC to ameliorate diabetic renal dysfunction and the associated pathologies of this disease might be due to its antioxidant capacity and suppression of the JAK2-STAT1/STAT3 cascade.

Journal ArticleDOI
TL;DR: The distribution of abnormal embryonic karyotype is a major factor related to RSA and further studies are needed to elucidate the etiology of RSA in order to achieve more effective prevention and treatment.
Abstract: Recurrent spontaneous abortion (RSA) is a multifactorial disease of which the exact causes are still unknown. In the current study, we aimed to analyze the distribution of abnormal embryonic karyotypes in RSA. 781 RSA patients of 17 hospitals in Shanghai from January 2014 to September 2016 were enrolled. Fetal villus tissues were collected during uterine curettage and then cultured in situ for karyotyping. All of the 781 cases were successfully cultured. There were 393 cases of abnormal karyotypes, accounting for 50.3% of the total cases. Women with abnormal embryonic karyotype were significantly older compared to those with normal karyotype (P < 0.001). The majority of patients with abnormal karyotype fell among age groups of 25-29 and 30-34. There were 247 cases of aneuploidy, accounting for 62.8% of the total abnormal karyotype cases. Autosomal trisomy was the primary form of aneuploidy (189/247, 76.5%), and the most common types were trisomy-16 (n = 69), trisomy-22 (n = 28), trisomy-21 (n = 21), trisomy-15 (n = 15), and trisomy-13 (n = 10). Abnormal karyotype is a major factor related to RSA. Further studies are needed to elucidate the etiology of RSA in order to achieve more effective prevention and treatment.

Journal ArticleDOI
TL;DR: A systematic review of recent data is conducted to examine the types and frequencies of dermatologic toxicities associated with anti-epidermal growth factor receptor (EGFR) therapies in NSCLC and mCRC and the management and treatment options currently used by clinicians based on the possible mechanism.
Abstract: The past decades have witnessed a rapid increase in the use of molecularly targeted therapies. One class of agents includes the epidermal growth factor receptor inhibitors (EGFRIs), which afford patients longer progression-free survival (PFS) times, especially among non-small cell lung cancer (NSCLC) and metastatic colorectal carcinoma (mCRC). Certain adverse effects, particularly skin toxicity, are mainly manifested as rash, xerosis, pruritus, nails changes, hair changes and mucositis. Previous studies reported the adverse events occurred based on the cutaneous inflammation reaction. Treatment recommended glucocorticoids and antibiotics. It is suggested that skin toxicity is an important issue because it usually affects patients' quality of life (QoL) and still causes dose reduction or discontinuation of targeted therapies. For these reasons, more and more oncologists and dermatologists recognize the importance of recognition and management of skin toxicities with the expansion in availability of EGFRIs. In this review, we conducted a systematic review of recent data to examine the types and frequencies of dermatologic toxicities associated with anti-epidermal growth factor receptor (EGFR) therapies in NSCLC and mCRC. In addition, we would like to explore the management and treatment options currently used by clinicians based on the possible mechanism.

Journal ArticleDOI
TL;DR: It is suggested cinobufacini could prevent HepG2 cells migration and invasion via inhibiting EMT through c-Met/ERK signaling pathway, which might provide experimental evidence for c inobufACini treatment of HCC.
Abstract: Cinobufacini, an aqueous extract from the skins and parotid venom glands of the toad Bufo bufo gargarizans Cantor, is a well known traditional Chinese medicine widely used in clinical cancer therapy in China. Its therapeutic effect is especially pronounced in liver cancer. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. Here, we investigated the effects and mechanisms of cinobufacini on inhibiting HepG2 cells invasion and metastasis. Epithelial-mesenchymal transition (EMT) is identified as an important initiation step for HCC metastasis. After the HepG2 cells were treated with different concentrations of cinobufacini, the expression of EMT related E-cadherin was increased while N-cadherin and Vimentin were decreased, and the expression of EMT related transcription factors Snail and Twist were decreased. Moreover, the phosphorylation of c-Met was inhibited by cinobufacini, and the expression of MEK1/2 and ERK1/2, the downstream kinase of the signal transduction pathway activated by c-Met, also decreased in a dose-dependent manner with cinobufacini. In addition, after the cells were treated with different concentrations of cinobufacini, there was a significant decrease in MMP-2 and MMP-9 expression in HepG2 cells. In conclusion, the current study suggested cinobufacini could prevent HepG2 cells migration and invasion via inhibiting EMT through c-Met/ERK signaling pathway, which might provide experimental evidence for cinobufacini treatment of HCC.

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TL;DR: The current results suggest that FL118 inhibited Wnt/β-catenin signaling, leading to suppressed EMT and decreased migration and invasion of breast cancer cells.
Abstract: The aim of the current study was to investigate the effects of FL118, a novel camptothecin analogue, on migration and invasion of human breast cancer cells and the underlying mechanisms of those effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a plate clone formation assay were used to examine inhibition of the proliferation of MDA-MB-231 cells by FL118. Cell cycle distribution was detected using flow cytometry. A wound healing assay and a transwell assay were performed to detect the effects of FL118 on migration and invasion of MDA-MB-231 cells, respectively. qRT-PCR, Western blotting, and immunocytochemistry were used to study the effects of FL118 on expression of epithelial-mesenchymal transition (EMT)-related molecules and Wnt/ β-catenin signaling components in MDA-MB-231 cells. The current results indicated that FL118 inhibited the proliferation, migration and invasion of MDA-MB-231 cells in a dose- and time-dependent manner. FL118 caused MDA-MB-231 cells to accumulate in the S phase. FL118 significantly suppressed the expression of vimentin while enhancing the expression of E-cadherin. Moreover, decreased expression of β-catenin and its targets survivin and cyclin Dl was detected in the nucleus of MDA-MB-231 cells. Taken together, the current results suggest that FL118 inhibited Wnt/β-catenin signaling, leading to suppressed EMT and decreased migration and invasion of breast cancer cells.

Journal ArticleDOI
TL;DR: Findings provide evidence that EESS suppresses RANKL-induced osteoclastogenesis and oxidative stress through suppression of NF-κB and activation of Nrf2/HO-1 signaling pathway, indicating that S. serratifolium has a potential application the prevention and treatment of osteOClastogenic bone disease.
Abstract: Sargassum serratifolium C Agardh is a marine brown alga that has long been used as an ingredient for food and medicine by many people living along Asian coastlines Recently, various beneficial effects of extracts or compounds isolated from S serratifolium have been reported, but their efficacies against bone destruction are unclear Therefore, in this study, we investigated the inhibitory property of an ethanol extract of S serratifolium (EESS) on osteoclast differentiation by focusing on the receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis model using RAW 2647 macrophages Our results demonstrated that EESS reduced RANKL-induced osteoclast differentiation in RAW 2647 cells, by inhibiting tartrate-resistant acid phosphatase (TRAP) activity and destroying the F-actin ring formation EESS also attenuated RANKL-induced expressions of key osteoclast-specific genes, such as nuclear factor of activated T cells cytoplasmic 1 (NFATC1), TRAP, cathepsin K and matrix metalloproteinase-9 These effects were mediated by impaired nuclear translocation of nuclear factor (NF)-κB and suppression of IκB-α degradation In addition, EESS effectively inhibited the production of reactive oxygen species (ROS) by RANKL, which was associated with enhanced expression of nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) Overall, our findings provide evidence that EESS suppresses RANKL-induced osteoclastogenesis and oxidative stress through suppression of NF-κB and activation of Nrf2/HO-1 signaling pathway, indicating that S serratifolium has a potential application the prevention and treatment of osteoclastogenic bone disease

Journal ArticleDOI
Zhen Wang1, Jianhui Wu1, Ang Lv1, Chengpeng Li1, Zhongwu Li1, Min Zhao1, Chunyi Hao1 
TL;DR: RPLS has a high infiltration tendency, such that it frequently infiltrates organs and surrounding fat tissue, and extended resection of the tumor and the adjacent organs is recommended.
Abstract: This study sought to evaluate the infiltration tendency of retroperitoneal liposarcoma (RPLS) from a new pathological angle by exploring the infiltration characteristics, which could provide helpful information to facilitate surgical decision-making and prognosis prediction. Concurrently, we aim to identify significant indicators of infiltration. A total of 61 consecutive patients with RPLS at our institution were retrospectively analyzed. All patients received extended surgery. The tumor infiltration characteristics and influencing factors were studied based on the pathological diagnosis. Univariate and multivariate analyses of organ infiltration (OI) and surrounding fat infiltration (SFI) were performed. OI was found in 95 (28.5%) resected organs from 39 (60.7%) patients, and SFI was found in 119 (35.7%) resected organs from 47 (77%) patients. The tumor infiltrated the serosal layer of 13 organs (13/37, 35.1%), the muscularis layer of 18 organs (18/37, 48.6%) and the submucosa of 6 organs (6/37, 16.2%). The percentage of lipoblasts and the rates of necrosis and mitosis were all significantly higher in high-grade tumors (dedifferentiated, round cell, and pleomorphic). A high lipoblast percentage (≥ 20%) was the only independent risk factor for OI. A recurrent tumor and a high-grade tumor were independent risk factors for SFI. In conclusion, RPLS has a high infiltration tendency, such that it frequently infiltrates organs and surrounding fat tissue. Therefore, extended resection of the tumor and the adjacent organs is recommended. The percentage of lipoblasts was associated with the tumor grade and infiltration characteristics; thus, lipoblast percentage may become a new grading factor for RPLS.

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TL;DR: M Mongolian echinops reduced bone loss and delayed the occurrence and development of osteoporosis, and increased ERα, ERβ, p-AKT, and P-ERK in BMSCs.
Abstract: Hormone replacement medicine such as traditional Chinese medicine has proven to be effective in decreasing the risk of osteoporosis. Mongolian medicine echinops prevents osteoporosis, but its mechanism remains unclear. In this study, we explored the mechanism underlying echinops prevents and treats postmenopausal osteoporosis. Osteoporosis model was established by ovariectomy in rats. Rats were treated to Echinops (16.26, 32.5, or 65 mg/kg/day) by oral gavage for 3 months. Bone mineral density (BMD) was detected by micro-CT detection of left proximal medial metaphyseal tibia. Hematoxylin and eosin (H&E) and toluidine blue O staining were also performed. Serum levels of E2, ALP and testosterone were examined. Bone marrow-derived bone marrow stem cells (BMSCs) were isolated and treated with echinops-containing serum. Estrogen receptors (ER) including ERα and ERβ in bone specimens and BMSCs were detected by qRT-PCR. Cell viability and colon formation of BMSCs were detected. Expressions of ERα, ERβ, AKT, p-AKT, ERK, and p-ERK in BMSCs were detected by western blot. Results showed that echinops significantly increased trabecular interconnectivity, thickness of trabeculae, and connection of trabecula. Echinops significantly increased BMD and E2, but significantly reduced ALP and testosterone in dose-dependent manners. Echinops induced ERα and ERβ in both bone specimens and BMSCs. Echinops enhanced cell viability and ability of colony formation of BMSCs, and increased ERα, ERβ, p-AKT, and p-ERK. Thus, Mongolian echinops reduced bone loss and delayed the occurrence and development of osteoporosis, and increased ERα, ERβ, p-AKT, and P-ERK in BMSCs. These results provide experimental basis for clinical prevention and treatment of postmenopausal osteoporosis by echniops.

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TL;DR: Improving the air quality, especially decreasing PM2.5 and PM10 could decrease the risk of HFMD outbreaks, and the addition of the air-quality factors could make the model better, improving MAE nearly 16.7%.
Abstract: Hand, foot, and mouth disease (HFMD) is caused by a group of enteroviruses. It infects millions of children in the Southeast Asian area. An accurate forecasting of outbreaks of HFMD could facilitate public health officials to suggest public health actions earlier. Many researchers tried to develop an early warning system for HFMD to lower the damage caused by a HFMD outbreak. The research data based on daily level could help figure out the relationship between HFMD and environmental factors, but nevertheless is difficult to collect. In this study, we collected the daily clinical data from the Shenzhen Health Information Center and multiple environmental factors to analyze the outbreaks of HFMD. Considering the incubation period of HFMD, we fed the previous 60 days' HFMD rates, 7 days' temperature factors and 7 days' air-quality factors into the tree model, XGBoost. The following conclusions were drawn in this study: i) Compared with the model only using the previous HFMD rate and temperature factors, the addition of the air-quality factors could make the model better, improving MAE nearly 16.7%. ii) By analyzing the Pearson correlation, we found that the temperature showed a positive correlation and the air quality showed a negative correlation for the HFMD outbreaks. Improving the air quality, especially decreasing PM2.5 and PM10 could decrease the risk of HFMD outbreaks.

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TL;DR: Mechanically, these lncRNAs participate in the EMT-related metastatic process in multiple ways including interaction with polycomb repressive complex 2 (PRC2), regulation of EMT signaling networks, mediation of E MT-transcription factors (EMT-TFs) and EMT markers, and cooperation with microRNAs (miRNAs).
Abstract: Gynecologic cancer is a vital global healthcare issue with high rates of mortality and morbidity. Tumor metastasis attributes to most of the death suffering from solid tumors. The epithelial-mesenchymal transition (EMT) plays a pivotal role in initiating metastasis. Long non-coding RNAs (lncRNAs), a well-known group of non-coding RNAs, and a prominent topic in life science research, are misregulated in many malignancies and some are EMT-associated. In the case of gynecologic cancers, several EMT-associated lncRNAs have been identified and found to be implicated in cancer aggressiveness and progression. Mechanically, these lncRNAs participate in the EMT-related metastatic process in multiple ways including interaction with polycomb repressive complex 2 (PRC2), regulation of EMT signaling networks, mediation of EMT-transcription factors (EMT-TFs) and EMT markers, and cooperation with microRNAs (miRNAs). Further studies on these EMT-associated lncRNAs and identification of more relevant lncRNAs are imperative for the lncRNAs-based clinical management of high rate of metastasis in patients with gynecologic cancers.

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TL;DR: It is suggested that CRP is the most effective biomarker among daily blood examination by using ROC curve analysis, suggesting that nivolumab treatment may be more effective for malignant melanoma with stronger inflammation.
Abstract: Biomarkers to distinguish patients with advanced melanoma responsive to nivolumab are of great interest. Therefore, we examined the possibility that laboratory data of daily blood examination become novel biomarkers. Laboratory data of 16 melanoma patients who were treated with nivolumab were retrospectively analyzed. Patients were classified as responder group or non-responder group. Examined were: white blood cell count (WBC), absolute lymphocyte counts (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute eosinophil count (AEC), and absolute basophil count (ABC), as well as levels of lactate dehydrogenase (LDH), C-reactive protein (CRP), one hour value of erythrocyte sedimentation rate (ESR), and 5-S-cysteinydopa (5-S-CD). Responder group showed significantly higher baseline levels of ESR or CRP and significantly lower ALC level before nivolumab treatment. Additionally, nivolumab treatment decreased the levels of CRP, ESR, and ANC, while it increased ALC level in the responder group. CRP was the most effective in distinguishing responder group from non-responder group both before and during treatment, according to the receiver operating characteristic (ROC) curve. We firstly showed that ESR is also the baseline biomarker of the efficacy of nivolumab. Furthermore, we confirmed that CRP is useful to predict the efficacy both before and during the treatment, and suggested that CRP is the most effective biomarker among daily blood examination by using ROC curve analysis. There is a possibility that nivolumab treatment may be more effective for malignant melanoma with stronger inflammation.

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TL;DR: The findings highlight the importance of the needs of individualized IPV interventions for certain target risk groups of MSM, although its association with HIV infection is not conclusive in this sample.
Abstract: Intimate partner violence (IPV) and its association with HIV infection among men who have sex men (MSM) in China are not understood. In this study, 732 MSM recruited from Shanghai, China between March and August 2015 were administered with a questionnaire survey and HIV blood testing. IPV victimization was measured by 25 forced-choice items capturing lifetime experience of physical, sexual, psychological, deprivation or neglect, and other forms of violence. Of them, 179 (24.3%) reported having experienced at least one type of IPV victimization. In separate multivariable analyses, sexual violence was associated with age over 35 years (AOR = 0.26, 95% CI: 0.07-1.02), ever had male-to-male commercial sex (AOR = 2.53, 95%CI: 1.19-5.39), and diagnosis of a sexually transmitted infection (STI) (AOR = 2.14, 95%CI: 0.98-4.66). Both psychological violence (AOR = 2.53, 95%CI: 1.25-5.12)and deprivation or neglect violence (AOR = 1.75, 95%CI: 1.14-2.68) were associated with ever had sex with a casual male partner(s). Having experienced at least one type of IPV victimization was significantly associated with ever had sex with a causal partner(s) (AOR = 1.72, 95%CI: 1.15-2.57) and ever had a diagnosis of a STI (AOR = 1.80, 95% CI: 1.12-2.88). HIV infection was marginally associated with having experienced any form of IPV victimization. IPV victimization is common among MSM, especially young MSM, in China, although its association with HIV infection is not conclusive in our sample. Nonetheless, our findings highlight the importance of the needs of individualized IPV interventions for certain target risk groups of MSM.