bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral and injectable Marsdenia tenacissima extract (MTE) as adjuvant therapy to chemotherapy for gastric cancer: a systematic review
Authors: Zhou Xu , Liu Meilu , Ren Qing , Zhu Weifeng , Wang Yang , Chen Haochen , Chen Jianrong
Published: December 2019

Background

Marsdenia tenacissima extract (MTE) is a phytochemical widely used as complementary therapy in cancer care. This systematic review was conducted to investigate the anticancer and detoxification effects of MTE, as an adjuvant therapy to chemotherapy, for treating gastric cancer.

Methods

Ten databases were searched to identify randomized controlled trials (RCTs) comparing oral or injectable MTE plus chemotherapy versus chemotherapy alone for treating gastric cancer up to May 1, 2019. In meta-analyses, proportional odds ratios (PORs) with 95% confidence intervals (CIs) were pooled for the ordinal outcomes using the generalized linear model, and risk ratios (RRs) with 95% CIs were pooled for dichotomous outcomes using the Mantel-Haenszel method.

Results

Seventeen RCTs with 1329 individuals were included, with a moderate to high risk of selection and performance bias. Compared to chemotherapy alone, MTE adjuvant therapy significantly improved the response to anticancer treatment (POR 2.01, 95% CI 1.60–2.53) and patients’ performance status (POR 3.15, 95% CI 2.22–4.48) and reduce the incidences of chemotherapy-induced leukopenia (RR 0.66, 95% CI 0.56–0.78), thrombocytopenia (RR 0.64, 95% CI 0.48–0.86), anemia (RR 0.89, 95% CI 0.72–1.10), nausea/vomiting (RR 0.79, 95% CI 0.69–0.91), hepatic injury (RR 0.77, 95% CI 0.61–0.96), and peripheral neurotoxicity (RR 0.77, 95% CI 0.59–1.01). However, MTE did not significantly alleviate anemia, diarrhea, constipation, kidney injury, and oral mucosal lesions after chemotherapy. Incidence of nausea/vomiting was lower in patients receiving oral MTE than those receiving injectable MTE (RR 0.47 vs. 0.82, interaction P = 0.04). Heterogeneity was generally low among these outcomes. Three out of five RCTs that reported survival data supported the effects of MTE for prolonging progression-free and/or overall survival. No studies reported safety outcomes of MTE.

Conclusions

The current evidence with limitations of risk of selection and performance bias suggests that MTE, as an adjuvant therapy to chemotherapy, is effective for inhibiting cancer growth and reducing incidences of multiple chemotherapy side effects. Oral MTE may be a better choice. Uncertainty remains regarding the effects of MTE on survival endpoints and the subgroup differences between acute and chronic use of MTE and between different chemotherapy regimens.
SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation
Authors: Zhang Yan , Zheng Liwei , Le Michael , Nakano Yukiko , Chan Barry , Huang Yulei , Torbaty Parisa Moravedje , Kohwi Yoshinori , Marcucio Ralph , Habelitz Stefan , Den Besten Pamela K. , Kohwi-Shigematsu Terumi
Published: December 2019

Background

Polarity is necessary for epithelial cells to perform distinct functions at their apical and basal surfaces. Oral epithelial cell-derived ameloblasts at secretory stage (SABs) synthesize large amounts of enamel matrix proteins (EMPs), largely amelogenins. EMPs are unidirectionally secreted into the enamel space through their apical cytoplasmic protrusions, or Tomes’ processes (TPs), to guide the enamel formation. Little is known about the transcriptional regulation underlying the establishment of cell polarity and unidirectional secretion of SABs.

Results

The higher-order chromatin architecture of eukaryotic genome plays important roles in cell- and stage-specific transcriptional programming. A genome organizer, special AT-rich sequence-binding protein 1 (SATB1), was discovered to be significantly upregulated in ameloblasts compared to oral epithelial cells using a whole-transcript microarray analysis. TheSatb1−/−mice possessed deformed ameloblasts and a thin layer of hypomineralized and non-prismatic enamel. Remarkably,Satb1−/−ameloblasts at the secretory stage lost many morphological characteristics found at the apical surface of wild-type (wt)SABs, including the loss of Tomes’ processes, defective inter-ameloblastic adhesion, and filamentous actin architecture. As expected, the secretory function ofSatb1−/−SABs was compromised as amelogenins were largely retained in cells. We found the expression of epidermal growth factor receptor pathway substrate 8 (Eps8), a known regulator for actin filament assembly and small intestinal epithelial cytoplasmic protrusion formation, to be SATB1 dependent. In contrast towtSABs, EPS8 could not be detected at the apical surface ofSatb1−/−SABs.Eps8expression was greatly reduced in small intestinal epithelial cells inSatb1−/−mice as well, displaying defective intestinal microvilli.

Conclusions

Our data show that SATB1 is essential for establishing secretory ameloblast cell polarity and for EMP secretion. In line with the deformed apical architecture, amelogenin transport to the apical secretory front and secretion into enamel space were impeded inSatb1−/−SABs resulting in a massive cytoplasmic accumulation of amelogenins and a thin layer of hypomineralized enamel. Our studies strongly suggest that SATB1-dependentEps8expression plays a critical role in cytoplasmic protrusion formation in both SABs and in small intestines. This study demonstrates the role of SATB1 in the regulation of amelogenesis and the potential application of SATB1 in ameloblast/enamel regeneration.
Blocking AMPK/ULK1-dependent autophagy promoted apoptosis and suppressed colon cancer growth
Authors: Liu Jing , Long Shuaiyu , Wang Huanan , Liu Nannan , Zhang Chuchu , Zhang Lingling , Zhang Yingjie
Published: December 2019

Background

Autophagy is an evolutionarily conserved process through which cells degrade and recycle cytoplasm. The relation among autophagy, apoptosis and tumor is highly controversial until now and the molecular mechanism is poorly understood.

Methods

Cell viability and apoptosis were detected by CCK8, crystal violet staining, Hoechst333342 staining and flow cytometry. The expression of AMPK and ULK1 was analyzed by western blotting. Colon cancer growth suppression by NVP-BEZ235 or CQ in vivo was studied in a tumor xenograft mouse model.

Results

Our previous study revealed that NVP-BEZ235 suppressed colorectal cancer growth via inducing apoptosis, however later, we found it also initiated autophagy simultaneously. In this present study, our results show that NVP-BEZ235 induced autophagy through AMPK/ULK1 pathway in colon cancer cells. Blocking autophagy by knocking down AMPK or ULK1 inhibited cell proliferation and further promoted NVP-BEZ235 induced apoptosis. Meantime, the autophagy inhibitor chloroquine (CQ) shows obvious effect on inhibiting cell proliferation but not on inducing apoptosis, while it significantly increased NVP-BEZ235 induced apoptosis. Furthermore, the combinational therapy of NVP-BEZ235 and CQ shows synergistic antitumor effects in colon cancer in vivo.

Conclusion

NVP-BEZ235 induced AMPK/ULK1-dependent autophagy. Targeting this autophagy suppressed colon cancer growth through further promoting apoptosis, which is a potential therapeutic option for clinical patients.
The reciprocal regulation between host tissue and immune cells in pancreatic ductal adenocarcinoma: new insights and therapeutic implications
Authors: Liu Xiaomeng , Xu Jin , Zhang Bo , Liu Jiang , Liang Chen , Meng Qingcai , Hua Jie , Yu Xianjun , Shi Si
Published: December 2019

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and is one of the most difficult-to-treat cancers. Surgical resection and adjuvant therapy have limited effects on the overall survival of PDAC patients. PDAC exhibits an immunosuppressive microenvironment, the immune response predicts survival, and activation of immune system has the potential to produce an efficacious PDAC therapy. However, chimeric antigen receptor T (CAR-T) cell immunotherapy and immune checkpoint blockade (ICB), which have produced unprecedented clinical benefits in a variety of different cancers, produce promising results in only some highly selected patients with PDAC. This lack of efficacy may be because existing immunotherapies mainly target the interactions between cancer cells and immune cells. However, PDAC is characterized by an abundant tumor stroma that includes a heterogeneous mixture of immune cells, fibroblasts, endothelial cells, neurons and some molecular events. Immune cells engage in extensive and dynamic crosstalk with stromal components in the tumor tissue in addition to tumor cells, which subsequently impacts tumor suppression or promotion to a large extent. Therefore, exploration of the interactions between the stroma and immune cells may offer new therapeutic opportunities for PDAC. In this review, we discuss how infiltrating immune cells influence PDAC development and explore the contributions of complex components to the immune landscape of tumor tissue. The roles of stromal constituents in immune modulation are emphasized. We also predict potential therapeutic strategies to target signals in the immune network in the abundant stromal microenvironment of PDAC.
Potentially modifiable blood triglyceride levels by the control of conventional risk factors
Authors: Oh Bumjo , Sung Joohon , Chun Sohyun
Published: December 2019

Backgrounds

Triglyceride (TG) is known to be regulated by multiple lifestyle factors rather than genetic factors. This cross-sectional and community-based study (Healthy Twin study in Korea) aimed to estimate the “modifiable TG level” by identifying non-genetic risk factors of TG.

Methods

Participants were recruited between 2006 and 2011 who fulfilled health examinations and detail surveys: 3079 Korean adults including 949 monozygotic twins and 222 dizygotic twins. In order to investigate conventional risk factors, a mixed model accounting for family as a random effect was performed. In addition, we conducted a co-twin control analysis for 452 monozygotic twin (MZ) pairs, to examine non-genetic risk factors and potentially modifiable serum triglyceride levels.

Results

After excluding patients on dyslipidemia or diabetes medication, 2672 individuals (1029 men, with mean age of 43.9; and 1643 women with mean age of 43.3; 949 MZ pairs, 222 dizygotic twin pairs, and 1501sibling pairs) were analyzed. Fasting blood sugar (FBS), lipid panel, height, weight, waist (WC) and hip circumference, body mass index (BMI), amount of dietary intake and amount of physical activity was examined after adjusting for age and sex. For conventional analysis, WC, fat %, and BMI were identified as significant factors influencing serum triglyceride levels. Examination of non-genetic factors from the Co-twin control study revealed BMI (beta coefficient 9.94 with C.I. 3.42 to 16.46) and amount of alcohol intake (beta coefficient 0.08 with C.I. 0.02 to 0.14) as significant factors.

Conclusion

Our findings suggest that controlling body weight and alcohol intake might be effective to control TG; moderate weight control (BMI 1 reduction) and reducing alcohol consumption by 50 g/week (about two glassed of beer) might reduce TG level by 9.94 and 4.0 mg/dL.
Emerging evidences for the opposite role of apolipoprotein C3 and apolipoprotein A5 in lipid metabolism and coronary artery disease
Authors: Dai Wen , Zhang Ziyu , Yao Chun , Zhao Shuiping
Published: December 2019

Apolipoprotein C3 (apoC3) and apolipoprotein A5 (apoA5), encoded byAPOA1/C3/A4/A5gene cluster, are two critical regulators of plasma triglyceride (TG) metabolism. Deficiency of apoC3 or apoA5 led to significant decreased or increased plasma TG levels, respectively. Recent studies indicated apoC3 and apoA5 also played roles in plasma remnant cholesterol, high density lipoprotein (HDL) and hepatic TG metabolisms. Moreover, large scale population genetic studies indicated that loss of function mutations inAPOC3andAPOA5gene conferred decreased and increased risk of coronary artery disease (CAD), respectively. This manuscript mainly reviewed existing evidences suggesting the opposite role of apoC3 and apoA5 in lipid metabolism and CAD risk, and discussed the potential correlation between these two apolipoproteins.
Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis
Authors: Atanasov Georgi , Dino Karoline , Schierle Katrin , Dietel Corinna , Aust Gabriela , Pratschke Johann , Seehofer Daniel , Schmelzle Moritz , Hau Hans-Michael
Published: December 2019

Background

Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC).

Methods

In this retrospective study, 58 HCC patients received surgery with a curative intent. The abundance of TEMs, angiopoietin-1 and -2 were detected in tumor specimens of the HCC patients (n = 58), and together with the occurrence of histologic tumor necrosis, were associated with established clinicopathological characteristics and survival.

Results

Patients with HCC characterized by necrosis and TEMs revealed reduced both overall survival and recurrence-free survival (all p < 0.05). Angiopoietins and TEMs were associated with metastatic and recurrent HCC. Furthermore, the formation of histologic tumor necrosis was associated with advanced tumor stage and density of TEMs (all p < 0.05).

Conclusions

Histologic tumor necrosis, TEMs, and related angiopoietins were associated with multiple HCC parameters and patient survival. The tumor necrosis–TEM–angiopoietin axis may offer a novel diagnostic modality to predict patient outcome after surgery for HCC.
Trends and risk factors of mortality analysis in patients with inflammatory bowel disease: a Taiwanese nationwide population-based study
Authors: Lin Wei-Chen , Weng Meng-Tzu , Tung Chien-Chih , Chang Yuan-Ting , Leong Yew-Loong , Wang Yu-Ting , Wang Horng-Yuan , Wong Jau-Min , Wei Shu-Chen
Published: December 2019

Background

Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients.

Methods

This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan’s National Health Insurance.

Results

Between 2001 and 2015, a total of 3806 IBD patients [Crohn’s disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02–4.55) and 1.44 (95% CI 1.26–1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011–2015 and 2001–2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD.

Conclusion

For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.
FXR activation alleviates tacrolimus-induced post-transplant diabetes mellitus by regulating renal gluconeogenesis and glucose uptake
Authors: Li Ling , Zhao Huijia , Chen Binyao , Fan Zhipeng , Li Ning , Yue Jiang , Ye Qifa
Published: December 2019

Background

Tacrolimus (FK506)-induced diabetes mellitus is one of the most important factors of post-transplant diabetes mellitus (PTDM). However, the detailed mechanisms underlying PTDM are still unclear. Farnesoid X receptor (FXR) regulates glycolipid metabolism. The objective of this study was to explore whether FXR is involved in the development of tacrolimus-induced diabetes mellitus.

Methods

After C57BL/6J mice were treated with tacrolimus (FK506) for 3 months, the fasting blood glucose levels, body weights, renal morphological alterations, and mRNA expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2) among the control group, the FK506 group and the FK506 + GW4064 (a FXR agonist) group (n = 7) were measured. The intracellular location of peroxisome proliferator activated receptor γ coactivator-1α (PGC1α) and forkhead box O1 (FOXO1) was detected by immunofluorescence. Human renal cortex proximal tubule epithelial cells (HK-2) were treated with 15 μM FK506 or 4 μM FXR agonist (GW4064) for 24, 48 and 72 h, and the expression levels of FXR, gluconeogenesis and glucose uptake, representing the enzymes PEPCK and GLUT2, were detected with real-time PCR and western blot analyses. Finally, the mRNA levels of PEPCK and GLUT2 in HK-2 cells were measured after FXR was upregulated.

Results

FK506 significantly inhibited the mRNA and protein levels of FXR at 48 h and 72 h in HK-2 cells (P < 0.05). Meanwhile, FK506 promoted gluconeogenesis and inhibited glucose uptake in HK-2 cells (P < 0.05). However, overexpression of FXR in transfected HK-2 cell lines significantly inhibited gluconeogenesis and promoted glucose uptake (P < 0.05). The FXR agonist GW4064 significantly decreased the fasting blood glucose in mice challenged with FK506 for 3 months (P < 0.05), inhibited gluconeogenesis (P < 0.05) and significantly promoted glucose uptake (P < 0.05). Immunofluorescence staining and western blot analyses further revealed that FXR activation may affect the translocation of PGC1α and FOXO1 from the nucleus to the cytoplasm.

Conclusions

FXR activation may mitigate tacrolimus-induced diabetes mellitus by regulating gluconeogenesis as well as glucose uptake of renal cortex proximal tubule epithelial cells in a PGC1α/FOXO1-dependent manner, which may be a potential therapeutic strategy for the prevention and treatment of PTDM.
The combination of CXCL9, CXCL10 and CXCL11 levels during primary HIV infection predicts HIV disease progression
Authors: Yin Xiaowan , Wang Zhuo , Wu Tong , Ma Meichen , Zhang Zining , Chu Zhenxing , Hu Qinghai , Ding Haibo , Han Xiaoxu , Xu Junjie , Shang Hong , Jiang Yongjun
Published: December 2019

Background

Chemokines are small chemotactic cytokines involved in inflammation, cell migration, and immune regulation in both physiological and pathological contexts. Here, we investigated the profile of chemokines during primary HIV infection (PHI).

Methods

Fifty-four participants with blood samples before and during HIV infection and clinical information available were selected from an HIV-negative man who have sex with men (MSM) prospective cohort. Thirty chemokines and 10 cytokines were measured pre- and post-HIV infection in the same individuals using a Bio-Plex Pro™ Human Chemokine Panel.

Results

Levels of 18 chemokines/cytokines changed significantly during PHI relative to pre-HIV infection levels; 14 were up-regulated and 4 down-regulated. Among them, CXCL9, CXCL10, and CXCL11 were the most prominently raised. Levels of CXCL9 and CXCL10 were much higher in the high-set point group (log viral load (lgVL) ≥ 4.5) than those in the low-set point group (lgVL < 4.5) and levels of CXCL9, CXCL10, and CXCL11 were higher in the low-CD4+T-cell count group (CD4+T-cell count ≥ 500). A formula to predict HIV disease progression using a combination panel comprising CXCL9, CXCL10, and CXCL11 was developed, where risk score = 0.007 × CXCL9 + 0.004 × CXCL10 − 0.033 × CXCL11 − 1.724, with risk score values higher than the cutoff threshold (0.5211) indicating more rapid HIV disease progression.

Conclusions

A panel of plasma CXCL9, CXCL10, and CXCL11 measured during primary HIV-1 infection could predict long-term HIV disease prognosis in an MSM group and has potential as a novel biomarker in the clinic.
Electroacupuncture attenuates cognition impairment via anti-neuroinflammation in an Alzheimer’s disease animal model
Authors: Cai Mudan , Lee Jun-Hwan , Yang Eun Jin
Published: December 2019

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive abilities and memory leading to dementia. Electroacupuncture (EA) is a complementary alternative medicine approach, applying an electrical current to acupuncture points. In clinical and animal studies, EA causes cognitive improvements in AD and vascular dementia. However, EA-induced changes in cognition and microglia-mediated amyloid β (Aβ) degradation have not been determined yet in AD animals. Therefore, this study investigated the EA-induced molecular mechanisms causing cognitive improvement and anti-inflammatory activity in five familial mutation (5XFAD) mice, an animal model of AD.

Methods

5XFAD mice were bilaterally treated with EA at the Taegye (KI3) acupoints three times per week for 2 weeks. To evaluate the effects of EA treatment on cognitive functions, novel object recognition and Y-maze tests were performed with non-Tg, 5XFAD (Tg), and EA-treated 5XFAD (Tg + KI3) mice. To examine the molecular mechanisms underlying EA effects, western blots, immunohistochemistry, and micro-positron emission tomography scans were performed. Furthermore, we studied synapse ultrastructures with transmission electron microscopy and used electrophysiology to investigate EA effects on synaptic plasticity in 5XFAD mice.

Results

EA treatment significantly improved working memory and synaptic plasticity, alleviated neuroinflammation, and reduced ultrastructural degradation of synapses via upregulation of synaptophysin and postsynaptic density-95 protein in 5XFAD mice. Furthermore, microglia-mediated Aβ deposition was reduced after EA treatment and coincided with a reduction in amyloid precursor protein.

Conclusions

Our findings demonstrate that EA treatment ameliorates cognitive impairment via inhibition of synaptic degeneration and neuroinflammation in a mouse model of AD.
Professional barriers and facilitators to using stratified care approaches for managing non-specific low back pain: a qualitative study with Canadian physiotherapists and chiropractors
Authors: AL Zoubi Fadi M. , French Simon D. , Patey Andrea M. , Mayo Nancy E. , Bussières André E.
Published: December 2019

Background

Recent clinical practice guidelines for the management of non-specific low back pain (LBP) recommend using stratified care approaches. To date, no study has assessed barriers and facilitators for health professionals in using stratified care approaches for managing non-specific LBP in the Canadian primary care setting. This study aimed to identify and contrast barriers and facilitators to using the stratified care approaches for non-specific LBP among Canadian physiotherapists and chiropractors.

Methods

Individual telephone interviews, underpinned by the Theoretical Domains Framework (TDF), explored beliefs and attitudes about, and identified barriers and facilitators to the use of stratified care approaches for managing non-specific LBP in a purposive sample of 13 chiropractors and 14 physiotherapists between September 2015 and June 2016. Interviews were digitally recorded, transcribed verbatim and analysed by two independent assessors using directed content analysis.

Results

Three and seven TDF domains were identified as likely relevant for physiotherapists and chiropractors, respectively. Shared key beliefs (and relevant domains of the TDF) for both physiotherapists and chiropractors included: lack of time, cost, and expertise (Environmental Context and Resources);and consulting more experienced colleagues and chronic patients with important psychological overlay (Social Influences).Unique key domains were identified among physiotherapists: incompatibility with achieving other objectives (Goals), and chiropractors: confidence in using stratified care approaches (Beliefs about Capabilities);intention to use stratified care approaches (Intentions);awareness and agreement with stratified care approaches (Knowledge);assessment of readiness for change and intentional planning behaviour (Behavioural Regulation);and improving the management of non-specific LBP patients and the uptake of evidence-based practice (Beliefs about Consequences).

Conclusions

Several shared and unique barriers and facilitators to using the stratified care approaches for non-specific LBP among Canadian physiotherapists and chiropractors were identified. Findings may help inform the design of tailored theory-based knowledge translation interventions to increase the uptake of stratified care approaches in clinical practice.
High shear stress suppresses proliferation and migration but promotes apoptosis of endothelial cells co-cultured with vascular smooth muscle cells via down-regulating MAPK pathway
Authors: Ji Qiang , Wang Yu Lin , Xia Li Min , Yang Ye , Wang Chun Sheng , Mei Yun Qing
Published: December 2019

Background

Early neointimal hyperplasia of vein graft may be ameliorated via enhancing intravenous surface shear stress. Cellular processes including proliferation, apoptosis and migration of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) may play very important roles in the process of neointimal hyperplasia of vein graft; and mitogen-activated protein kinase (MAPK) pathways including extracellular signal-regulated kinase (ERK1/2) and p38 pathways play vital roles in regulating a large variety of cellular processes. This study evaluated the impacts of shear stress and MAPK pathways on cellular processes of ECs in a co-culture system with VSMCs, and aimed to test the hypothesis that high shear stress suppresses proliferation and migration but promotes apoptosis of ECs co-cultured with VSMCs via down-regulating MAPK pathway.

Methods

Primary ECs and VSMCs derived from porcine great saphenous vein were collected, respectively. 4–7 generation of cells were used as work cells. ECs and VSMCs were co-cultured and synchronized under high and low shear stress using Parallel-Plate Flow Chamber system. And then, ECs co-cultured with VSMCs were incubated with U0126 (ERK1/2 inhibitor) or PD98059 (p38 inhibitor) under different shear stress. Proliferation, apoptosis and migration of ECs in a co-culture system with VSMCs were detected by 4,5-dimethyl-2-thiazolyl (MTT) assay and bromodeoxyuridine (BrdU) assay, fluorescent-activated cell sorting (FACS) technique, and Transwell assay separately. Each test repeated 3 times. Additionally, protein expressions of ERK1/2 and p38 MAPK were detected by using Western blot, respectively.

Results

Under higher level of shear stress condition, proliferation and migration of ECs co-cultured with VSMCs were suppressed, while cell apoptosis was promoted. And blocking ERK1/2 pathway by U0126 or blocking p38 pathway by PD98059, proliferation and migration of ECs co-cultured with VSMCs were further suppressed, while cell apoptosis was further promoted. Additionally, protein expressions of phosphorylation of ERK1/2 and p38MAPK were decreased under higher level of shear stress condition, and were further reduced by blocking ERK1/2 or p38 pathway under shear stress condition.

Conclusions

High shear stress may suppress proliferation and apoptosis of ECs in a co-culture system with VSMCs but promote cell migration via down-regulating ERK1/2 and p38 MAPK pathways.
Persistently elevated alpha-fetoprotein associated with chronic hepatitis B during chemotherapy for malignant ovarian germ cell tumors: a case series and a review of the literature
Authors: Zong Xuan , Yang Jia-Xin , Zhang Ying
Published: December 2019

Background

Alpha-fetoprotein (AFP) plays a crucial role in the management of malignant ovarian germ cell tumors (MOGCTs) and is an important reference index for chemotherapy termination. However, a high level of AFP can also be caused by several benign diseases, causing confusion and impacting treatment decisions.

Case presentation

We described four patients who were diagnosed with MOGCTs; the histologic subtype in two of them was mixed MOGCTs (yolk sac tumor with mature teratoma), while the rest was immature teratoma. The serum AFP level of each patient was abnormal before surgery, but it was still persistently elevated around 300 ng/ml even after additional cycles of chemotherapy. All patients were thoroughly evaluated, but we did not find any evidence of disease progression or residual tumors. Liver function tests were normal, whereas serum assays revealed positive of hepatitis B surface antigen, and two patients had a high level of HBV-DNA. They were chronic carriers of hepatitis B virus and never received relevant treatments. Then they were managed with tumor surveillance and the antiviral treatment. Thereafter, the AFP levels presented a slowly decreasing trend.

Conclusions

False elevation of AFP in MOGCTs is a rare condition and should be assessed with a comprehensive evaluation to avoid unnecessary treatments.
Hyaluronic acid and platelet-rich plasma, a new therapeutic alternative for scleroderma patients: a prospective open-label study
Authors: Pirrello Roberto , Verro Barbara , Grasso Giulia , Ruscitti Piero , Cordova Adriana , Giacomelli Roberto , Ciccia Francesco , Guggino Giuliana
Published: December 2019

Background

Systemic sclerosis is a systemic connective tissue disease characterized by endothelium damage, fibrosis, and subsequent atrophy of the skin. Perioral fibrosis produces a characteristic microstomia together with microcheilia, both of which cause severe difficulties and affects patients’ daily life, such as eating and oral hygiene. Since there are no effective and specific therapies, we have aimed at evaluating the response to filler injections of hyaluronic acid together with platelet-rich plasma.

Methods

Ten female patients aged between 18 and 70 were included in this study. Each patient was treated with three filler injections of hyaluronic acid and platelet-rich plasma at an interval of 15 to 20 days. Follow-up check-ups were recorded 1, 3, and 24 months after the end of the treatment. During the therapy and the subsequent follow-up, we evaluated the mouth’s opening, freedom of movement of the lips, and skin elasticity.

Results

After the treatment, patients had achieved good results already after the first injection and the improvement was maintained in the following months, up to 2 years. In particular, 8 (80%) patients showed a greater mouth’s opening and increased upper lip’s thickness during 1-month follow-up and maintained these results after 2 years (maximum mouth’s opening T0 47.61; T3 49.23; T4 48.60p <  0.0001. Upper lip’s thickness T0 4.20; T3 4.75; T4 4.45p <  0.0001). Moreover, distance between upper and lower incisors (T0 27.05; T3 29.03; T4 28.14p < 0.0001), inter-commissural distance (T0 49.12; T3 51.44; T4 50.31:p < 0.0001), and lower lip’s thickness (T0 3.80; T3 4.85, 5.10; T4 4.25;p < 0.0001) were increased in all of patients in 1-month follow-up, keeping these benefits after 24 months and having a significant increase of skin elasticity 1 month after the end of therapy.

Conclusions

Our study demonstrates that filler injections of hyaluronic acid and platelet-rich plasma represent an efficient local therapeutic alternative for patients affected by scleroderma. The treatment has significantly improved patients’ quality of living.
Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis
Authors: Oto Yohsuke , Takahashi Yukari , Kurosaka Daitaro , Kato Fusao
Published: December 2019

Background

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis and bone destruction at the joints, causing pain and motor disturbance. Despite the better control of inflammation and joint deformity afforded by modern disease-modifying anti-rheumatic drugs, many patients with RA remain dissatisfied with their treatment, primarily because of sensory-emotional distress. Pre-clinical tests that can evaluate not only the symptoms of arthritis but also the associated pain as sensory-emotional experience are urgently needed.

Methods

Here, we introduce two types of novel methods for evaluation of voluntary behavior in a commonly used model of RA (collagen-induced arthritis; CIA) in male mice. First, spontaneous motor activity was assessed with a running wheel placed in home cages and the number of rotations was continuously recorded in a 12:12-h light environment. Second, temperature preference was assessed by measuring the time spent in either of the floor plates with augmenting (25 to 49 °C) or fixed temperature (25 °C). We also evaluated the effects of tofacitinib on CIA-associated changes in voluntary wheel running and temperature preference.

Results

We detected a significant decrease in voluntary wheel running, a significant shift in the distribution of movement in the dark phase, and a significant increase in the time spent in warmer environments than the room temperature in the mice with CIA. These alterations in voluntary behavior have never been described with conventional methods. We also revealed tofacitinib-resistant significant changes in the voluntary behavior and choice of temperature despite significant mitigation of the symptoms of arthritis.

Conclusions

We described for the first time significant alterations of the voluntary behavior of the mice with CIA during the clinical periods, indicating that the overall physical/motivational states and its circadian variation, as well as the specific preference to a certain environmental temperature, are modified in the mice with CIA, as observed in human patients. Some of these did not parallel with the conventional arthritis scores, particularly during the pharmacotherapy suggesting that mice with CIA show not only the peripheral symptoms but also the central consequences. The use of these approaches would also help clarify the biological mechanisms underlying physician-patient discordance in the assessment of RA.
Relatively young T1D adults using fixed doses of insulin have higher diabetes distress levels in a sample of patients from a Brazilian tertiary hospital
Authors: Silveira M. S. V. M. , Bovi T. G. , Pavin E. J.
Published: December 2019

Background

Elevated rates of anxiety and depressive symptoms in Type 1 Diabetes patients (T1D) and high rates of diabetes-specific distress (DD) have been shown. Several factors may be responsible for increase the DD levels such as age, life changes, lack of familiar support, education, insulin regimens (IRs) and chronic complications. The goals of this study were: 1—to compare DD levels, anxiety and depressive symptoms according to age (< and ≥ 25 years old), 2—to evaluate the association between DD levels, anxiety and depressive symptoms and IRs, and 3—to evaluate the association between DD levels, anxiety and depressive symptoms and chronic complications.

Methods

In a cross-sectional study, T1D patients receiving outpatient care at Unicamp tertiary hospital were included. Inclusion criteria were age at least 18 years old and diagnosis of T1D for 6 months. Exclusion criteria were cognitive impairment, major psychiatric disorders, severe diabetes-related complications, and pregnancy. Depressive symptoms were evaluated by the depression subscale of the Hospital Anxiety and Depression Scale (HAD-D) and the anxiety symptoms by the anxiety subscale of the same instrument (HAD-A). DDS scale assessed DD. Glycemic control was evaluated by HbA1C. The latest lipid panel results were recorded and IRs and chronic complications were obtained through chart review.

Results

Of all 70 patients, 70% were younger than 25 years old. No differences were found between two groups according to gender, education, and income (p = 0.39, p = 0.87, and p = 0.52, respectively). HbA1c mean was 10% in both groups (p = 0.15). Older patients had higher levels of total DD and physician DD than younger (p = 0.0048 and p = 0.0413; respectively).Total DD and DD on subscales 1 and 2 were higher in patients using fixed doses of insulin compared to variable doses according to carbohydrates count (p = 0.0392, p = 0.0383 and p = 0.0043, respectively). No differences were found between anxiety and depressive symptoms and age and IRs. Similarly, no differences were found among DD levels, anxiety and depressive symptoms in patients with and without chronic complications.

Conclusions

When providing education and care for T1D patients, health providers should consider age, patient’s developmental stage, with its related demands and the burden of insulin regimen.
Lycopene improves on basic hematological and immunological parameters in diabetes mellitus
Authors: Eze Ejike Daniel , Afodun Adam Moyosore , Kasolo Josephine , Kasozi Keneth Iceland
Published: December 2019

Objective

Diabetes is associated with an upset of hematological and immunological parameters in humans, however information on the effects of Lycopene is scarce. The aim of the study was to gain information on basic changes in hematological parameters as markers for safety since anemia as a complication in diabetic chemotherapy has been reported.

Results

Lycopene had anti-anemic effects and improved on the immune status of diabetic rats and these observations were dose independent. There was a decrease in neutrophil, low neutrophil–lymphocyte ratio and platelet counts and stable albumin, globulin levels. Lycopene could exert its protective effects through a balance of basic hematological physiological variables.
ECDU: an edge content delivery and update framework in Mobile edge computing
Authors: Ding Chuntao , Zhou Ao , Huang Jie , Liu Ying , Wang Shangguang
Published: December 2019

Content delivery network (CDN) has gained increasing popularity in recent years for facilitating content delivery. Most existing CDN-based works upload the content generated by mobile users to the cloud data center firstly. Then, the cloud data center delivers the content to the proxy server. Finally, the mobile users request the required content from the proxy server. However, uploading all the collected content to the cloud data center increases the pressure on the core network. In addition, it also wastes a lot of bandwidth resources because most of the content does not have to be uploaded. To make up for the shortcomings of existing CDN-based works, this article proposes an edge content delivery and update (ECDU) framework based on mobile edge computing architecture. In the ECDU framework, we deploy a number of content servers to store raw content collected from mobile users, and cache pools to store content that frequently requested at the edge of the network. Thus, it is not necessary to upload all content collected by mobile users to the cloud data center, thereby alleviating the pressure of the core network. Based on content popularity and cache pool ranking, we also propose edge content delivery (ECD) and edge content update (ECU) schemes. The ECD scheme is to deliver content from cloud data center to cache pool, and the ECU scheme is to mitigate the content to appropriate cache pools in terms of its request frequency and cache pool ranking. Finally, a representative case study is provided and several open research issues are discussed.
The effectiveness of psychological interventions for fatigue in cancer survivors: systematic review of randomised controlled trials
Authors: Corbett T. K. , Groarke A. , Devane D. , Carr E. , Walsh J. C. , McGuire B. E.
Published: December 2019

Background

Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase. This systematic review evaluated the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors.

Methods

We searched relevant online databases and sources of grey literature. Randomised controlled trials (RCTs) evaluating psychological interventions in adult cancer patients after the completion of treatment, with fatigue as an outcome measure, were included. Two review authors extracted data independently from the selected studies and assessed the methodological quality using the Cochrane Collaboration Risk of Bias Tool.

Results

Thirty-three psychological interventions were identified. The sample size of the included studies varied between 28 and 409, with 4525 participants overall. Twenty-three of the included studies reported a significant effect of the interventions on reducing fatigue in cancer survivors. Most interventions focused on psychoeducation, mindfulness, cognitive or behaviour therapy-oriented strategies. However, studies differed widely in terms of measurement tools used to assess fatigue, mode, duration and frequency of the intervention delivery.

Conclusions

This review showed some tentative support for psychological interventions for fatigue after cancer treatment. However, as the RCTs were heterogeneous in nature and the number of high-quality studies was limited, definitive conclusions are not yet possible. With the growing need for stage-specific research in cancer, this review sought to inform current practice and to summarise the existing evidence base of randomised controlled trials in the area.

Systematic review registration

PROSPERO registration number: CRD42014015219.
Recovery rate and determinants of severe acute malnutrition children treatment in Ethiopia: a systematic review and meta-analysis
Authors: Yazew Kassahun Gebeyehu , Kassahun Chanyalew Worku , Ewnetie Amare Wondim , Mekonen Habtamu Kerebih , Abagez Endalamaw Salilew
Published: December 2019

Background

Severe acute malnutrition affects more than 20 million children. Africa is pointed out as a region where the problem is highly prevalent. There were individual studies on the recovery rate and its determinants among children with severe acute malnutrition in Ethiopia. But, there is no national pooled estimate. Therefore, this systematic review and meta-analysis aimed to estimate the recovery rate and determinants among children with severe acute malnutrition admitted to the therapeutic feeding unit in Ethiopia.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed in this study. Studies were accessed through electronic web-based search from PubMed, Cochrane Library, Google Scholar, and EMBASE. The statistical analysis was conducted using STATA version-11 software. The pooled prevalence was estimated with 95% confidence intervals using a random-effects model.

Result

A total of 12 studies were included with 2658 participants in the analysis. The overall pooled estimated recovery rate among children with severe acute malnutrition admitted to the inpatient therapeutic feeding unit in Ethiopia was 72.02 % (CI, 64.83, 79.22%). In the subgroup analysis, the highest estimate (80.29%) was observed in studies conducted in Oromia regional state, while 68.63% was observed in studies Southern Nation Nationality of people region 68.63%. Children who had no congestive heart failure were 4.88 times (OR, 4.88; 95% CI, 2.246, 10.586) more likely to recover than their counterparts.

Conclusion

The recovery rate among severe acute malnourished children on the therapeutic feeding unit in Ethiopia lied within the international minimum sphere. Hence, health care providers shall strengthen the management of severe acute malnutrition and management other co-morbidities like congestive heart failure.

Systematic review registration

PROSPEROCRD42019119124
On n-quasi-$[m,C]$-isometric operators
Authors: Shen Junli
Published: December 2019

For positive integers m and n, an operator $T \in B ( H )$T∈B(H) is said to be an n-quasi-$[m,C]$[m,C]-isometric operator if there exists some conjugation C such that T∗n(∑j=0m(−1)j(mj)CTm−jC.Tm−j)Tn=0. In this paper, some basic structural properties of n-quasi-$[m,C]$[m,C]-isometric operators are established with the help of operator matrix representation. As an application, we obtain that a power of an n-quasi-$[m,C]$[m,C]-isometric operator is again an n-quasi-$[m,C]$[m,C]-isometric operator. Moreover, we show that the class of n-quasi-$[m,C]$[m,C]-isometric operators is norm closed. Finally, we examine the stability of n-quasi-$[m,C]$[m,C]-isometric operator under perturbation by nilpotent operators commuting with T.
Multiple periodic solutions for damped vibration systems with superquadratic terms at infinity
Authors: Li Ping , Chen Guanwei
Published: December 2019

By using variational methods, we obtain infinitely many nontrivial periodic solutions for a class of damped vibration systems with superquadratic terms at infinity. By using some weaker conditions, our results extend and improve some existing results in the literature. Besides, some examples are given to illustrate our results.
Re-estimating the changes and ranges of forest biomass carbon in China during the past 40 years
Authors: Zhou Xiaolu , Lei Xiangdong , Liu Caixia , Huang Huabing , Zhou Carl , Peng Changhui
Published: December 2019

Background

In recent decades the future of global forests has been a matter of increasing concern, particularly in relation to the threat of forest ecosystem responses under potential climate change. To the future predictions of these responses, the current forest biomass carbon storage (FCS) should first be clarified as much as possible, especially at national scales. However, few studies have introduced how to verify an FCS estimate by delimiting the reasonable ranges. This paper addresses an estimation of national FCS and its verification using two-step process to narrow the uncertainty. Our study focuses on a methodology for reducing the uncertainty resulted by converting from growing stock volume to above- and below-ground biomass (AB biomass), so as to eliminate the significant bias in national scale estimations.

Methods

We recommend splitting the estimation into two parts, one part for stem and the other part for AB biomass to preclude possible significant bias. Our method estimates the stem biomass from volume and wood density (WD), and converts the AB biomass from stem biomass by using allometric relationships.

Results

Based on the presented two-step process, the estimation of China’s FCS is performed as an example to explicate how to infer the ranges of national FCS. The experimental results demonstrate a national FCS estimation within the reasonable ranges (relative errors: + 4.46% and − 4.44%), e.g., 5.6–6.1 PgC for China’s forest ecosystem at the beginning of the 2010s. These ranges are less than 0.52 PgC for confirming each FCS estimate of different periods during the last 40 years. In addition, our results suggest the upper-limits by specifying a highly impractical value of WD (0.7 t∙m− 3) on the national scale. As a control reference, this value decides what estimate is impossible to achieve for the FCS estimates.

Conclusions

Presented methodological analysis highlights the possibility to determine a range that the true value could be located in. The two-step process will help to verify national FCS and also to reduce uncertainty in related studies. While the true value of national FCS is immeasurable, our work should motivate future studies that explore new estimations to approach the true value by narrowing the uncertainty in FCS estimations on national and global scales.