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Epithelial growth factor receptor (EGFR), as a malignancy marker, is overly expressed in multiple solid tumors including colorectal neoplasms, one of the most prevalent malignancies worldwide. The main objective of this study is to enhance the efficacy of anti-tumor therapy targeting EGFR by constructing a novel EGFR-specific immunotoxin (C-CUS245C) based on Cetuximab and recombinant Cucurmosin (CUS245C). E. coli BL21 (DE3) PlysS (E. coli) was used to express CUS245C with a cysteine residue inserting to the C-terminus of Cucurmosin. Then immobilized metal ion affinity chromatography (IMAC) was used to purify CUS245C. The chemical conjugation method was used for the preparation of C-CUS245C. Then dialysis and IMAC were used to purify C-CUS245C. Western blot as well as SDS-PAGE was carried out to characterize the formation of C-CUS245C. At last the anti-colorectal cancer activity of C-CUS245C was investigated in vitro and in vivo. CUS245C with high purity could be obtained from the prokaryotic system. C-CUS245C was successfully constructed and highly purified. The cytotoxicity assays in vitro showed a significant proliferation inhibition of C-CUS245C on EGFR-positive cells for 120 h with IC50 values less than 0.1 pM. Besides, the anti-tumor efficacy of C-CUS245C was remarkably more potent than that of Cetuximab, CUS245C, and C + CUS245C (P

To evaluate the changes in left ventricular myocardial function in patients with colorectal cancer undergoing chemotherapy with mFOLFOX6 (oxaliplatin + 5-fluorouracil + calcium folinate) using three-dimensional speckle-tracking echocardiography (3D-STE). Data were collected from 30 patients diagnosed with colorectal cancer in our hospital treated with mFOLFOX6. We used 3D-STE to measure the following parameters of left ventricle function: global longitudinal strain (GLS), global area strain (GAS), global circumferential strain (GCS), global radial strain (GRS), and left ventricular twist (LVtw). Myocardial composite index (MCI) was calculated from measured values (MCI = GLS × LVtw). The above listed parameters were compared before and after chemotherapy. Receiver operating curves (ROC) were prepared for each parameter and analyzed to identify correlations among MCI, LVEF, GLS, and cTnT. Compared with the pre-chemotherapy state, the absolute values of MCI, LVtw, GLS, GAS, GCS, and GRS decreased with increasing cumulative doses of chemotherapeutic drugs. The absolute values of GAS, GLS, MCI, and LVtw decreased after the first cycle of chemotherapy (P

Immunotoxins are Ab‐cytotoxin chimeric molecules with mighty cytotoxicity. Programmed cell death 1‐ligand 1 (PD‐L1), is a transmembrane protein expressed mainly in inflammatory tumor tissues and plays a pivotal role in immune escape and tumor progression. Although PD‐L1 immune checkpoint therapy has been successful in some cases, many patients have not benefited enough due to primary/secondary resistance. In order to optimize the therapeutic efficacy of anti‐PD‐L1 mAb, we used durvalumab as the payload and CUS245C, a type I ribosome‐inactivating protein isolated from Cucurbita moschata, as the toxin moiety, to construct PD‐L1‐specific immunotoxin (named D‐CUS245C) through the engineered cysteine residue. In vitro, D‐CUS245C selectively killed PD‐L1+ tumor cells. In vivo studies also showed that D‐CUS245C had obvious antitumor effect on PD‐L1+ human xenograft tumors in nude mice. In conclusion, in the combination of the toxin with mAb, this study developed a new immunotoxin targeting PD‐L1, emphasizing a novel and promising treatment strategy and providing a valuable way to optimize cancer immunotherapy., Programmed cell death 1‐ligand 1 is a potential target for immunotoxins. Synthesis and purification of a chemically conjugated immunotoxin D‐CUS245C kills the cells mediated by the apoptosis pathway and shows potent antitumor activity both in vitro and in vivo.

Ultra–wide-field imaging and ultra–wide-field intravenous fundus fluorescein angiography using Optos 200Tx reveal the characteristics of retinopathy of prematurity at different stages, which have the potential to screen, diagnose, and follow-up for retinopathy of prematurity., Purpose: To determine the feasibility of ultra–wide-field imaging and ultra–wide-field intravenous fundus fluorescein angiography (UWF-IV-FFA) in infants with retinopathy of prematurity (ROP) using Optos 200Tx. Methods: We performed Optos 200Tx capturing on 32 premature infants (14 females) and UWF-IV-FFA with Optos 200Tx on 12 of the 32 infants between April 2017 and July 2018 at the affiliated eye hospital of Wenzhou Medical University and analyzed their fundus images. Results: Ultra–wide-field color images were acquired from 32 infants (64 eyes). UWF-IV-FFA was performed successfully in 12 premature infants (24 eyes). No adverse events were observed. The ultra–wide-field Optos 200Tx color images and UWF-IV-FFA images revealed Stages 1, 2, and 3 ROP and aggressive posterior ROP. Conclusion: Ultra–wide-field imaging and intravenous fundus fluorescein angiography using Optos 200Tx are feasible in infants with ROP, which have the potential to screen, diagnose, and follow-up for ROP.

Purpose: To quantitatively assess the retinal capillary vessel density (VD) and foveal avascular zone (FAZ) area in acute and chronic central serous chorioretinopathy (CSC) patients compared to healthy subjects using optical coherence tomography angiography (OCTA) and determine their correlation with visual acuity (VA). Methods: This was a cross-sectional, case-control study. All subjects were divided into three groups: acute CSC, chronic CSC, and healthy controls. The best-corrected VA test, optical coherence tomography, and OCTA were performed on the same day. In this study, we recorded and compared the main data of FAZ and VD in 3 × 3 mm OCTA images among three groups, also calculated the correlation between OCTA variables and VA in CSC patients. Results: A total of 148 subjects (148 eyes) were included in this study, with 50 eyes in acute CSC, 48 eyes in chronic CSC, and 50 eyes in control groups. The mean age was 50.11 ± 8.14 years. Chronic CSC had the significantly lowest VD both on the superficial and deep retina and the largest FAZ (0.39 ± 0.13 mm2) compared to acute CSC and controls (all p < 0.05). There was no statistical difference between acute CSC and controls on VD or FAZ (both p > 0.05). In chronic CSC, both the decreased VD on deep retina and expanded FAZ were correlated with a worse VA (both p < 0.05). Conclusions: OCTA could serve as a reliable tool to evaluate different courses of CSC quantitively. In 3 × 3 mm OCTA images, both decreased VD and expanded FAZ were observed in chronic CSC patients.

Macrophage-derived exosomes have been implicated on the modulation of inflammatory processes. Recent studies have shown that macrophage-derived exosomes contribute to the progression of many diseases such as cancer, atherosclerosis, diabetes and heart failure. This review describes the biogenesis of macrophage-derived exosomes and their biological functions in different diseases. In addition, the challenges facing the use of macrophage-derived exosomes as delivery tools for drugs, genes, and proteins in clinical applications are described. The application of macrophage-derived exosomes in the diagnosis and treatment of diseases is also discussed.

SUMMARY: Resveratrol is a polyphenol known to have many beneficial biological activities. In our study, we investigated the effect of supplementing chicken feed with different concentrations of resveratrol. A total of 2,160 Jingfen white egg chickens in their 210-d old were selected for this study. They were randomly distributed into 4 diet groups with 6 replicates each. Each replicate group contained 90 chickens. Diets were supplemented with 1 of 4 doses of resveratrol: 0, 200, 400, and 800 mg/kg. Relative to that in controls, the egg production rate and mean daily food intake significantly increased upon 200 mg/kg resveratrol treatment (P < 0.05). The feed-to-egg ratio also significantly diminished in these animals (P < 0.05), as did the cull/death rate. Resveratrol was also linked with extended egg shelf lives and improved sensory scores. Supplementation with 400 mg/kg resveratrol significantly reduced levels of total serum cholesterol and triglycerides and activities of alanine transaminase and aspartate transaminase (P < 0.05). These results therefore show that 200 mg/kg resveratrol supplementation improved the performance of laying hens, whereas 400 mg/kg dose was associated with better lipid metabolism, reduced egg cholesterol content, extended egg shelf life, improved antioxidant activity, and improved egg sensory scores.

BACKGROUND To define a new quantitative grading criterion for retinal haemorrhages in term newborns based on the segmentation results of a deep convolutional neural network. METHODS We constructed a dataset of 1543 retina images acquired from 847 term newborns, and developed a deep convolutional neural network to segment retinal haemorrhages, blood vessels and optic discs and locate the macular region. Based on the ratio of areas of retinal haemorrhage to optic disc, and the location of retinal haemorrhages relative to the macular region, we defined a new criterion to grade the degree of retinal haemorrhages in term newborns. RESULTS The F1 scores of the proposed network for segmenting retinal haemorrhages, blood vessels and optic discs were 0.84, 0.73 and 0.94, respectively. Compared with two commonly used retinal haemorrhage grading criteria, this new method is more accurate, objective and quantitative, with the relative location of the retinal haemorrhages to the macula as an important factor. CONCLUSIONS Based on a deep convolutional neural network, we can segment retinal haemorrhages, blood vessels and optic disc with high accuracy. The proposed grading criterion considers not only the area of the haemorrhages but also the locations relative to the macular region. It provides a more objective and comprehensive evaluation criterion. The developed deep convolutional neural network offers an end-to-end solution that can assist doctors to grade retinal haemorrhages in term newborns.

Background and aim Recent clinical trials have confirmed that Helicobacter pylori infection is positively associated with nonalcoholic fatty liver disease (NAFLD), although some research has shown a negative association. Therefore, to confirm whether H. pylori eradication treatment is feasible for NAFLD patients in our hospital, we aimed to establish the association between H. pylori infection and NAFLD. Methods We enrolled 91 patients with NAFLD diagnosed by abdominal B-mode ultrasonography between January and December 2018. H. pylori infection was confirmed by C13 urea breath test, and liver function, glycometabolism, insulin sensitivity, lipid metabolism, as well as inflammatory reaction were assessed through blood biochemical analyses. Results A minority of NAFLD patients had liver dysfunction, increased fasting glucose and insulin levels, a score of insulin-resistance (HOMA-Ir), lipid metabolism, slight inflammatory response, fasting hyperglycemia and hypertension. Most patients were complicated with overweight/visceral obesity and dyslipidemia. Moreover, these abnormal indicators were closely associated with the severity of NAFLD and H. pylori infection. Notably, the prevalence of H. pylori infection showed a significant difference between mild, moderate and severe NAFLD, and hepatic steatosis with coexistent NAFLD also revealed a striking difference between H. pylori-positive and H. pylori-negative patients (P

Background: There has been increased interest in the research of proteasome inhibitors for more than two decades. Hotspots in this field are constantly changing. Objective: This study aimed to investigate trends in proteasome inhibitors research from 1992 to 2018 and compare the contributions of such research from different countries and authors. Methods: We used Excel 2013 and VoSviewer to analyze bibliometric data on the subject of proteasome inhibitors, including the number of publications, citations frequency, H-index, and country contributions and hotspots (keywords of popular scientific fields). Results: A total of 3646 articles were included. The USA contributed the largest percentage of articles (1742), with the most citations (90666) and the highest H-index (139). The journal Blood had the most articles. Dana Farber Cancer Institute and Millennium Pharmaceuticals Incorporation were the most contributive institutions. Keywords could be divided into three clusters: Basic experiment, clinical research, and others. Conclusion: The number of proteasome inhibitors articles has been increasing for the past 27 years. The USA made the largest contribution in this field. Recent studies on the topic of “carfilzomib” are relatively new and should be closely followed in proteasome inhibitors research.

Objective: Tanshinone IIA (TSN) and Tetramethylpyrazine (TMP) were combined in a composite, oil-in-water nanoemulsions (TSN/TMP O/W NEs) was prepared to prolong in vitro and vivo circulation time, and enhance the bioavailability of TSN. Material and methods: Physicochemical characterization of TSN/TMP O/W NEs was characterized systematically. The in vitro dissolution and in vivo pharmacokinetic experiments of TSN/TMP O/W NEs were also evaluated. Result: A formulation was optimized, yielding a 32.5 nm average particle size, an encapsulation efficiency of over 95 %, and were spherical in shape as shown by TEM. TSN/TMP O/W NEs were shown to extend the release and availability in vitro compared to raw compounds. In pharmacokinetic study, the AUC0→∞ and t1/2 of the TSN/TMP O/W NEs were 481.50 mg/L*min and 346.39 min higher than TSN solution, respectively. Brain tissue concentration of TSN was enhanced with TSN/TMP O/W NEs over raw TSN and even TSN O/W NEs. Conclusions: Therefore, nanoemulsions are an effective carrier to increase encapsulation efficiency of drugs, improve bioavailability and brain penetration for TSN – which is further enhanced by pairing with the co-delivery of TMP, providing a promising drug delivery.

Objective: To improve the water solubility and enhance the oral bioavailability of gambogenic acid (GNA).Methods: GNA-phospholipid complex (GNA-PLC) micelles were successfully prepared by anti-solv...

Objectives Gambogenic acid (GNA), one of the main active ingredients isolated from Garcinia cambogia, has shown diverse antitumour activities. However, short biological half-life and low oral bioavailability severely limit its clinical application. Here, we developed GNA-loaded zein nanoparticles (GNA-ZN-NPs) based on phospholipid complex and zein nanoparticles to prolong the circulation time and enhance oral bioavailability of GNA. Methods The physicochemical properties of GNA-ZN-NP were characterized in details. The in vitro release profile, in vivo pharmacokinetic experiments and tissue distribution of GNA-ZN-NPs were also evaluated. Key findings The particle size, PDI and encapsulation efficiency of GNA-ZN-NPs were 102.90 nm, 0.027 and 76.35 ± 0.64%, respectively. The results of SEM, FTIR, DSC and XRD demonstrated that GNA-ZN-NPs were prepared successfully. The in vitro dissolution of GNA-ZN-NPs exhibited controlled release compared with raw GNA solution. The pharmacokinetic study showed that the AUC of GNA-ZN-NPs was significantly increased, and the t1/2 and MRT values of GNA-ZN-NPs were 3.21-fold and 2.19-fold higher than that of GNA solution. Tissue distribution results illustrated that GNA-ZN-NPs showed hepatic-targeting properties. Conclusion GNA-ZN-NPs significantly enhanced the oral bioavailability and prolonged half-life of GNA, providing a promising oral drug delivery system to improve in vivo pharmacokinetic behaviour of GNA.

Purpose. To evaluate the efficacy and safety of conbercept for patients with chronic central serous chorioretinopathy (CSC). Methods. A retrospective clinical study. Thirty-one patients (35 eyes) with chronic CSC were given intravitreal injections of conbercept and followed up for at least 6 months. Observed indicators included best-corrected visual acuity (BCVA), central macular thickness (CMT), and resolution of subretinal fluid (SRF). Serial changes in BCVA and CMT were analyzed by using repeated measures analysis of variance. Results. During the 6-month follow-up, the mean number of injections required and performed was 1.77 ± 0.60. The logMAR BCVA was 0.48 ± 0.26 at the baseline, 0.34 ± 0.26, 0.30 ± 0.26, 0.27 ± 0.26, 0.24 ± 0.26, and 0.23 ± 0.26 at 2-week and 1-, 2-, 3-, and 6-month follow-ups, respectively (F = 27.173, P<0.05). CMT was 313.74 ± 144.51 μm at the baseline and decreased to 263.49 ± 120.44 μm, 225.91 ± 91.98 μm, 195.77 ± 66.69 μm, 189.74 ± 65.41 μm, and 199.49 ± 81.50 μm at 2-week and 1-, 2-, 3-, and 6-month follow-ups, respectively (F = 18.093, P<0.05). Full resolution of SRF was achieved in 8 (22.9%) eyes at 1 month, 16 (45.7%) eyes at 2 months, 22 (62.9%) eyes at 3 months, and 27 (77.1%) eyes at 6 months after the initial treatment of anti-VEGF injection. No severe adverse event was noted relevant to the therapy. Conclusions. Intravitreal injection of conbercept may effectively reduce the CMT and improve the BCVA in chronic CSC in a short term of 6 months.

Metformin hydrochloride (Met) is the first-line drug to treat type 2 diabetes and has shown high efficiency in reducing Alzheimer's disease in recent studies. Herein, a borneol W/O/W composite submicron emulsion containing Met (B-Met-W/O/W SE) was prepared, expecting longer in-vivo circulation time, better bioavailability and brain targeting of Met drug. In the optimized formulation, the mean droplets size, polydispersity index and encapsulation efficiency of the composite were 386.5 nm, 0.219 and 87.26%, respectively. FTIR analysis confirmed that Met interacted with carriers in B-Met-W/O/W SE. Compared with Met free drug, in-vitro release of Met in B-Met-W/O/W SE delivery system was much slower. In pharmacokinetic studies in rats, the AUC, MRT and t1/2 of the B-Met-W/O/W SE system were respectively 1.27, 2.49 and 4.02-fold higher than Met free drug system. The drug-targeting index of B-Met-W/O/W SE system to the brain tissue was also higher than that of Met free drug system and Met-W/O/W SE system. These results indicated that B-Met-W/O/W SE drug delivery system is a promising candidate in treating clinical Alzheimer's disease.

Aberrantly elevated expression levels of histone deacetylase 1 (HDAC1) and vimentin are closely associated with disease progression in hepatocellular carcinoma (HCC). It was previously demonstrated that knocking down expression of HDAC1 resulted in a concurrent decrease in the expression levels of vimentin. However, a causal link between these two proteins has not yet been demonstrated, to the best of our knowledge. In the present study, the association between HDAC1 and vimentin was investigated using an HDAC1 overexpression platform. HDAC1 and vimentin were significantly increased in HCC cells, and HDAC1 overexpression enhanced vimentin mRNA and protein expression levels in an HDAC1 dose-dependent manner. Subsequently, truncation and mutation of a vimentin promoter demonstrated that HDAC1-induced vimentin expression was dependent on a nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding site in the vimentin promoter sequence. Furthermore, HDAC1 induced vimentin expression by promoting NF-κB translocation between the cytoplasm and the nucleus, as opposed to modulating the total expression level of vimentin directly. The data in the present study demonstrated that HDAC1 is overexpressed in HCC and that HDAC1 may upregulate vimentin expression through the NF-κB signaling pathway, thus demonstrating a causal link between HDAC1 and vimentin in HCC, and may provide valuable information in understanding the pathogenesis of HCC.

Background Tongue squamous cell carcinoma (TSCC) is the second most common malignancy in oral carcinoma. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was regarded as an oncogenic factor in various carcinomas. However, its underlying molecular mechanisms in the development and progression of TSCC have not been well featured till now. Methods The expressions of MALAT1, miR-140-5p and p21 (RAC1)-activated kinase 1 (PAK1) mRNA were measured by RT-qPCR assay. The protein level of PAK1 was determined by western blot analysis. Cell viability was detected by Cell Counting Kit-8 assay. Transwell chamber was used to detect cell migratory and invasive capability. Luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and biotin pull-down assay were applied to evaluate the relationship between MALAT1, miR-140-5p and PAK1. Xenograft experiments were performed to assess the effect and mechanism of MALAT1 in TSCC tumor growth. Results The expression of MALAT1 and p21 (RAC1)-activated kinase 1 (PAK1) was upregulated and microRNA-140-5p (miR-140-5p) expression was downregulated in TSCC tissues and cells. MALAT1 knockdown induced miR-140-5p expression by direct interaction. Moreover, MALAT1 knockdown inhibited proliferation, migration, and invasion by upregulating miR-140-5p expression in TSCC cells. Additionally, PAK1 was identified as a direct target of miR-140-5p. Also, MALAT1 knockdown inhibited PAK1 expression by upregulating miR-140-5p in TSCC cells. Furthermore, miR-140-5p overexpression curbed the proliferation, migration, and invasion of TSCC cells by targeting PAK1. Finally, MALAT1 knockdown inhibited tumor growth by upregulating miR-140-5p and downregulating PAK1 in mouse xenograft models of TSCC. Conclusion MALAT1 contributed to TSCC progression via miR-140-5p-PAK1 regulatory axis, highlighting a potential target for TSCC management.

Background: The 2019 coronavirus disease (COVID-19) pandemic is a public health emergency of international concern. This study aimed to assess the psychological outcomes and their influencing factors among medical and non-medical University students during the COVID-19 pandemic in China.Methods: A cross-sectional online survey using structured questionnaires was conducted from February 20 to March 20, 2020. Psychological outcomes were assessed according to the Depression, Anxiety, and Stress Scale (DASS-21). Influencing factors were assessed by COVID-19 knowledge, mindful coping scale, and sense of control scale.Results: Our sample is comprised of 563 University students (male = 172, mean age = 21.52). Among them, 382 are medical students. Among the participants, 12.26, 18.47, and 8.53% have moderate to severe levels of depression, anxiety, and stress symptoms, respectively. Compared with the non-medical students, the medical students had a higher knowledge level of COVID-19, a higher sense of awareness, and fewer mental health symptoms. After controlling the covariance, perceived constraints of sense of control were negatively associated with depression, anxiety, and stress among both medical and non-medical students. Prevention of negative emotions by mindful coping was negatively associated with depression and anxiety among non-medical students. Knowledge of COVID-19 is not associated with mental distress among medical and non-medical students.Conclusions: During the COVID-19 pandemic in China, the mental health of University students was affected. Our findings suggested that a sense of control is a protective factor for both medical and non-medical students, while mindful coping is a protective factor for only non-medical students.

AIM: To compare the safety and efficacy of conbercept intravitreal injection and half-dose photodynamic therapy (PDT) in treating chronic central serous chorioretinopathy (CSC). METHODS: This study was retrospective. Thirty-seven patients (37 eyes) with chronic CSC received conbercept injections while 57 patients (57 eyes) were treated with half-dose PDT. All subjects were followed in 6mo. Outcome measures included change in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and resolution of subretinal fluid (SRF). RESULTS: There was no adverse event observed in either treatment group. At the 6-month follow-up, 26 eyes (70.3%) in the conbercept group and 54 eyes (94.7%) in the half-dose PDT group (P0.05). The SFCT also improved in all subjects (P

To enhance the water solubility, oral bioavailability, and tumor targeting of gambogenic acid (GNA), polydopamine nanoparticles (PDA NPs) were prepared to encapsulate and stabilize GNA surface modified by folic acid (FA) and then coated with sodium alginate (GNA@PDA-FA SA NPs) to achieve an antitumor effect by oral administration. GNA@PDA-FA SA NPs exhibited in vitro pH-sensitive release behavior. In vitro cell studies manifested that GNA@PDA-FA NPs had higher cytotoxicity to 4T1 cells compared with raw GNA (IC50 = 2.58 μM vs 7.57 μM). After being modified with FA, GNA@PDA-FA NPs were taken up easily by 4T1 cells. In vivo studies demonstrated that the area under the curve (AUC0→∞) of the plasma drug concentration-time of GNA@PDA-FA SA NPs was 2.97-fold higher than that of raw GNA, along with improving drug distribution in the liver, lung, and kidney tissues. In vivo anti-tumor experiments, GNA@PDA-FA SA NPs significantly inhibited the growth of breast tumors in the 4T1 xenograft breast cancer model via oral administration without obvious toxicity on major organs. Our studies indicated that the GNA@PDA-FA SA NPs modified with FA and coated with SA were a promising drug delivery system for targeting tumor therapy via oral administration.

Purpose The 2019 COVID-19 pandemic poses a challenge to adolescent psychological health. The aim of this study was to survey junior high and high school students in China to better understand the psychological consequences, such as anxiety, depression, and stress, of the COVID-19 pandemic. Methods A cross-sectional online survey using structural questionnaires was conducted from April 7, 2020, to April 24, 2020. Demographic information and general information related to the pandemic were collected. Psychological consequences were assessed by the Impact of Event Scale-Revised and the Depression, Anxiety and Stress Scale. Influencing factors were assessed by the Brief Resilience Scale and Coping Style Questionnaire. Results Our sample comprised 493 junior high school students (male = 239, mean age = 13.93 years) and 532 high school students (male = 289, mean age = 17.08 years). Resilience and positive coping were protective factors for the occurrence of depressive, anxiety, and stress symptoms in junior high and high school students (p < .05). Positive coping was a protective factor for trauma-related distress in junior high school students (p < .05). Negative coping is a risk factor for depression, anxiety, stress symptoms, and trauma-related distress in junior high and high school students (p < .05). Conclusions During the COVID-19 pandemic in China, more than one fifth of junior high and high school students' mental health was affected. Our findings suggested that resilience and positive coping lead to better psychological and mental health status among students. In contrast, negative coping is a risk factor for mental health.

Osteosarcoma (OSA), the malignant bone tumor, predominantly affecting children and adolescents, threatens the life and life quality of the patients. An increasing number of studies have indicated the role of long non-coding RNA (lncRNA) dysregulation in cancer biology. Herein, the study was aimed to explore the role of FGD5 antisense RNA 1 (FGD5-AS1), a lncRNA, in OSA. Expression levels of FGD5-AS1, miR-506-3p and RAB3D mRNA were quantified utilizing qRT-PCR. The expression of RAB3D protein was examined employing Western blot. A series of functional experiments including CCK-8 assay, BrdU assay, wound healing assay, Transwell assay were performed for studying the effects of FGD5-AS1 on the malignancy of OSA cell lines 143B and HOS. The binding site between miR-506-3p and FGD5-AS1 was identified and validated by luciferase reporter assay and RNA immunoprecipitation assay. It was demonstrated that the expression of FGD5-AS1 was up-regulated in OSA tissues and cell lines, and its high expression is associated with higher Enneking stage and poorer histological differentiation. Gain-of-function and loss-of-function studies suggested that FGD5-AS1 facilitated OSA cells proliferation and migration. The promoting effects of FGD5-AS1 overexpression on OSA cell proliferation and migration could be counteracted by miR-506-3p. Moreover, FGD5-AS1 competitively adsorbed miR-506-3p to repress its expression so as to up-regulate the expression of RAB3D. These results indicate that FGD5-AS1 is capable of expediting OSA cell proliferation and migration via sponging miR-506-3p to up-regulate RAB3D.

Objective To investigate the clinical value of three-dimensional speckle tracking imaging (3D-STI) in evaluating left ventricular (LV) systolic function in patients with ovarian cancer (OC) treated with paclitaxel and carboplatin. Method We studied 30 patients with OC treated with paclitaxel combined with carboplatin chemotherapy. Two-dimensional echocardiography and 3D-STI were performed in the patients before they underwent 2- and 6-cycle chemotherapies, and in 30 normal control subjects. Were measured LV end-diastolic volume (EDV), end-systolic volume (ESV), three-dimensional LV ejection fraction (3D-LVEF), stroke volume (SV), spherical index (SPI), LV end-diastolic mass (LV EDmass), LV end-systolic mass (LV ESmass), LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), global area strain (GAS) and cardiac troponin T(cTnT). At the end of chemotherapy, magnetic resonance imaging (MRI) was also performed. Result The 3D conventional strain values (3D-LVEF, SV, LV EDV) after the 2- and 6-cycle chemotherapy were lower than before chemotherapy. LV Edmass, LV ESmass and cTnT were higher while LV GLS, GCS, GRS, GAS were lower after 2- and after 6-cycle chemotherapy than before chemotherapy. There was no significant difference in ESV and EDV between the 3D-STI and MRI parameters. GAS showed a significant negative correlation with cTnT. MRI and 3D-STI variables were significantly correlated, and the receiver operating characteristic curves showed the greater area under the curve for GAS after 2- and after 6-cycle chemotherapy. After 2-cycle chemotherapy, the highest specificity for GAS was 93.3%, and the highest sensitivity for GLS was 70.0%. After 6-cycle chemotherapy, the highest specificity for GAS was 96.7%, and the highest sensitivity for GLS was 96.7%. Conclusion The LV systolic function decreased in OC patients treated with paclitaxel and carboplatin, showing that 3D-STI may detect early LV systolic dysfunction.

Epidermal growth factor receptor (EGFR) is overexpressed in various tumors and is associated with cancer initiation, progression, and poor prognosis. Despite the achievements made by tyrosine kinase inhibitors and monoclonal antibodies in certain cases, many patients have not benefited from such treatment due to resistance. Immunotoxins (ITs) are antibody-cytotoxin chimeric molecules with specific cell killing ability, which have achieved different degrees of success in the treatment of a wide range of cancers in clinical trials. The aim of the current study was to examine a novel targeting EGFR recombinant immunotoxin Bs/cucurmosin (CUS) generated by fusing CUS to the EGFR-specific nanobody 7D12-9G8. Bs/CUS was successfully expressed in Escherichia coli strain BL21 (DE3) in a soluble form. Furthermore, it retained binding capacity and specificity with EGFR and was superior to rE/CUS, a monospecific IT we reported previously. In vitro results showed that Bs/CUS could be internalized into the cytoplasm and selectively kill cells in the picomolar range. Flow cytometry showed that Bs/CUS killed the cells mediated by the apoptosis pathway. Taken together, results of the current study indicated that Bs/CUS is a promising candidate that should be further evaluated as a cancer therapeutic for the treatment of EGFR-positive tumors.

The transport protein particle (TRAPP) complex was initially identified as a tethering factor for COPII vesicle. Subsequently, three forms (TRAPPI, II, and III) have been found and TRAPPIII has been reported to serve as a regulator in autophagy. This study investigates a new role of mammalian TRAPPIII in ciliogenesis. We found a ciliopathy protein, oral-facial-digital syndrome 1 (OFD1), interacting with the TRAPPIII-specific subunits TRAPPC8 and TRAPPC12. TRAPPC8 is necessary for the association of OFD1 with pericentriolar material 1 (PCM1). Its depletion reduces the extent of colocalized signals between OFD1 and PCM1, but does not compromise the structural integrity of centriolar satellites. The interaction between TRAPPC8 and OFD1 inhibits that between OFD1 and TRAPPC12, suggesting different roles of TRAPPIII-specific subunits in ciliogenesis and explaining the differences in cilium lengths in TRAPPC8-depleted and TRAPPC12-depleted hTERT-RPE1 cells. On the other hand, TRAPPC12 depletion causes increased ciliary length because TRAPPC12 is required for the disassembly of primary cilia. Overall, this study has revealed different roles of TRAPPC8 and TRAPPC12 in the assembly of centriolar satellites and demonstrated a possible tethering role of TRAPPIII during ciliogenesis.

Objective: To determine the efficacy and safety of current maintenance therapies consisting of different regimens of long-acting β2-agonists (LABA) with inhaled corticosteroids (ICS) in patients wi...

Surgical preservation of laryngeal function is very challenging in patients with advanced SCCL, especially those of stage T4a. The purpose of this study was to assess the feasibility of organ preservation surgery for patients with T4a squamous cell carcinoma of the larynx (SCCL). We enrolled 32 patients with T4a SCCL and performed organ preservation surgery on them. Surgical details and perioperative morbidity were described, functional and oncologic outcomes were also evaluated. All patients underwent supracricoid subtotal laryngectomy with unilateral or bilateral neck dissection, restoring laryngeal function via direct anastomosis of the cricoid cartilage and tongue base. The patients recovered well and exhibited relatively acceptable survival duration, with a 5-year overall survival rate of 62.5%. Most patients commenced oral intake within 2 weeks, and aspiration was commonly observed. Subjective functional outcomes indicated a relatively acceptable swallowing function and voice quality. Our retrospective analysis of 32 patients with T4a SCCL showed that successful organ preservation surgery is safe and reliable, and associated with a relatively acceptable disease-free survival, normal swallowing function, and acceptable voice quality. More patients with T4a SCCL who wish to preserve the larynx should be considered for organ preservation surgery.

The pathogenesis of obstructive sleep apnea (OSA) remains controversial. The role of anatomic stenosis is indisputable, and neural regulation of the upper airway remains to be elucidated. The upper airway maintains patency through the upper airway reflex. Lesions in any link of the reflex can increase the collapsibility of the upper airway. In this study, we investigated sensorimotor nerve lesions and their possible relationship with OSA. Tissue samples were obtained from the pharyngopalatine arch in 47 patients with OSA and 45 control participants to examine changes in the expression levels of myelin basic protein (MBP) and agrin through immunohistochemistry and western blotting. Downregulation of MBP in the mucosa reflects myelinated degeneration of mucosal sensory nerve axons, whereas upregulation of agrin in the neuromuscular junction reflects synaptic regeneration following denervation. The two neural factors correlate significantly with polysomnographic parameters, such as the apnea hypopnea index and lowest oxygen saturation. Our findings suggest that sensorimotor nerve damage in the upper airway of patients with OSA may be associated closely with the mechanism of OSA.

The present study was performed to identify the dysregulated microRNAs (miRNAs/miRs) and mRNAs, and enriched pathways involved in nasopharyngeal carcinoma (NPC) through the establishment of an miRNA‑mRNA‑pathways network. mRNA and miRNA expression profiles were collected from the European Molecular Biology Laboratory‑European Bioinformatics Institute. Differentially expressed genes and differentially expressed miRNA were selectively screened using the metaDE package. Following prediction of the risk genes and pathway pairs involved in NPC, an miRNA‑mRNA‑pathway network was constructed by merging the miRNA‑mRNA pairs, the mRNA‑pathway pairs and the mRNA‑mRNA pairs. The miRNA and mRNA biomarkers, as well as the functional pathway pairs, were identified in the network analysis, based on the topological properties of nodes in the network. Additionally, 10‑fold cross‑validation was performed to evaluate the performance of the selected risk genes and their corresponding miRNA in NPC by calculating the area under the curve (AUC). In total, 99 upregulated and 841 downregulated genes, and 192 upregulated and 26 downregulated miRNAs were identified. The miRNA‑mRNA‑pathway network was established using 403 miRNA‑mRNA pairs, including 40 miRNAs and 302 risk genes, as well as 22 prominent pathway pairs. Network analysis demonstrated that v‑myc avian myelocytomatosis viral oncogene homolog (MYC) and hsa‑miR‑423‑5p were the mRNA and miRNA signatures for NPC, respectively. The AUC of these biomarkers for NPC was 0.7568 and 0.7798, respectively. Additionally, the focal adhesion pair pathway in cancer was identified to be associated with NPC. MYC and hsa‑miR‑423‑5p have been identified to be critical biomarkers in NPC as revealed by miRNA‑mRNA‑pathway network integrated analysis, suggesting a direction for further research into the diagnosis and treatment of NPC.

Aim: To target both head and neck squamous cell carcinoma (HNSCC) cells and cancer stem cells (CSCs) by salinomycin-loaded DSPE-PEG-MTX (synthesized using DSPE-PEG2000-NH2 and methotrexate) nanomicelles (M-SAL-MTX). Materials & methods: The characterization, antitumor activity and mechanism of M-SAL-MTX were evaluated. Results & conclusion: M-SAL-MTX showed enhanced inhibitory effect toward both HNSCC CSCs and non-CSCs compared with a single treatment of methotrexate and salinomycin. In nude mice-bearing HNSCC xenografts, M-SAL-MTX suppressed tumor growth more effectively than other controls including combination of methotrexate and salinomycin. Therefore, M-SAL-MTX may provide a strategy for treating HNSCC by targeting both HNSCC CSCs and HNSCC cells.

Background Intensive-care-unit-acquired weakness (ICU-AW) not only leads to difficulty weaning off mechanical ventilation, prolonged hospital stay and increased medical costs, but also reduces the patient’s quality of life after discharge and increases the 1-year mortality rate. Early identification and intervention can improve the prognosis of critically ill patients. However, much remains unknown about current clinical practice for ICU-AW assessment by ICU staff in China. Objectives To investigate current practices and barriers to ICU-AW assessment among ICU staff, and provide insights to improve ICU-AW assessment in ICUs in China. Methods Qualitative interviews were used to construct a survey questionnaire (test–retest reliability 0.92, validity 0.96). This survey was subsequently completed by 3206 ICU staff from 31 provinces, municipalities and autonomous regions in China. Results In total, 3206 ICU staff responded to the survey (response rate 90%): 616 doctors (19%), 2371 nurses (74%), 129 respiratory therapists (4%), 51 physiotherapists (2%) and 39 dieticians (1%). Only 27% of the respondents had treated/cared for patients with ICU-AW. Reported methods for ICU-AW assessment were clinical experience (53%), ICU-AW assessment tools (12%), and physiotherapy consultation (35%). Forty-three percent of respondents felt that their ICU-AW-related knowledge did not meet clinical needs, only 10% had received ICU-AW-related training, and 19% proactively assessed whether their patients had ICU-AW. In terms of frequency of assessment, 42%, 16% and 11% of respondents considered that ICU-AW should be assessed daily, every 3 days, and on ICU admission and discharge, respectively. The Medical Research Council scale, electrophysiological assessment and the Manual Muscle Testing scale were considered to be optimal tools for ICU-AW diagnosis by 44%, 17% and 11% of respondents, respectively. The main reported barriers to ICU-AW assessment were lack of knowledge, cognitive impairment among patients, and lack of ICU-AW assessment guidelines and procedures. Conclusion Current practices for ICU-AW assessment are non-specific, and the main barriers include lack of skills and knowledge.

BACKGROUND The purpose of this study was to develop an automated diagnosis and quantitative analysis system for plus disease. The system provides a diagnostic decision but also performs quantitative analysis of the typical pathological features of the disease, which helps the physicians to make the best judgement and communicate the decisions. METHODS The deep learning network provided segmentation of the retinal vessels and the optic disc (OD). Based on the vessel segmentation, plus disease was classified and tortuosity, width, fractal dimension and vessel density were evaluated automatically. RESULTS The trained network achieved a sensitivity of 95.1% with 97.8% specificity for the diagnosis of plus disease. For detection of preplus or worse, the sensitivity and specificity were 92.4% and 97.4%. The quadratic weighted k was 0.9244. The tortuosities for the normal, preplus and plus groups were 3.61 ± 0.08, 5.95 ± 1.57 and 10.67 ± 0.50 (104 cm-3 ). The widths of the blood vessels were 63.46 ± 0.39, 67.21 ± 0.70 and 68.89 ± 0.75 μm. The fractal dimensions were 1.18 ± 0.01, 1.22 ± 0.01 and 1.26 ± 0.02. The vessel densities were 1.39 ± 0.03, 1.60 ± 0.01 and 1.64 ± 0.09 (%). All values were statistically different among the groups. After treatment for plus disease with ranibizumab injection, quantitative analysis showed significant changes in the pathological features. CONCLUSIONS Our system achieved high accuracy of diagnosis of plus disease in retinopathy of prematurity. It provided a quantitative analysis of the dynamic features of the disease progression. This automated system can assist physicians by providing a classification decision with auxiliary quantitative evaluation of the typical pathological features of the disease.

Trastuzumab is a humanized monoclonal antibody against HER2 approved by FDA for breast and gastric cancer therapy. However, only a quarter of patients have the potential to benefit from it, and most of them develop resistance within therapy. The main purpose of this study is to broaden trastuzumab's therapeutic window by conjugating trastuzumab with recombinant cucurmosin to form an immunotoxin called T-CUS245C. T-CUS245C was chemically conjugated and the purification of T-CUS245C was evaluated by SDS-PAGE. SRB tests showed a remarkable cytotoxicity of T-CUS245C with IC50 values in picomolar range on HER2 positive cancer cells without significantly proliferation inhibition on HER2 negative cells (P

It has been widely considered that reversing epithelial-to-mesenchymal transition (EMT) is a potential access to restrain cancer progression and therapeutic resistance. Here, we aim to uncover the novel mechanisms by which we can reverse EMT and inhibit metastasis in laryngeal squamous cell carcinoma (LSCC). We show that miR-98 is significantly reduced in both LSCC specimens and cell lines. Over-expression of miR-98 inhibits the EMT-related gene expression and metastasis and invasive behavior in LSCC in vitro, as well as reduces lung metastasis in mouse model. In the mechanistically study, miR-98 directly targets HMGA2 in mediating EMT. HMGA2 knock down by si-RNA method declines several EMT-related genes expression and LSCC migration and invasion. In parallel, overexpression of HMGA2 transforms LSCC cells to acquire stem cell-like features. Furthermore, we reveal that HMGA2-mediated EMT is closely linked with the expression of POSTN that inhibits EMT, as a tumor suppressor, by gene profiling analyses. POSTN is transcriptionally repressed by HMGA2. In clinic, the HMGA2 mRNA level is negatively correlated with the miR-98 level in LSCC patient cohort. In conclusion, our study confers a powerful signal: miR-98-HMGA-POSTN in LSCC, which is able to reverse EMT and inhibit metastasis, underlining the therapeutic potential of this signal.

Early mobilization has been proven to be an effective and safe intervention for preventing complications in mechanically ventilated patients; however, there is currently no unified definition of the optimal mobilization initiation time, hindering widespread clinical implementation. As clinicians are increasingly aware of the benefits of early mobilization, the definition of early mobilization is important. The purpose of this study was to evaluate the effects of different early mobilization initiation times on mechanically ventilated patients and rank these times for practical consideration. The Chinese Biomedical Literature Database, the Chinese Knowledge Infrastructure, Wanfang Data, PubMed, Cochrane Library, Web of Science, and Embase databases, along with grey literature and reference lists, were searched for randomized control trials (RCTs) that evaluated the effects of early mobilization for improving patient outcomes; databases were searched from inception to October 2018. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook (v5.1.0). Data were analyzed using Stata (v13.0) and Review Manager (v5.3.0). A total of 15 RCTs involving 1726 patients and seven mobilization initiation times (which were all compared to usual care) were included in our analysis. Network meta-analysis showed that mechanical ventilation for 48–72 h may be optimal to improve intensive care unit acquired weakness (ICU-AW) and reduce the duration of mechanical ventilation; however, there were no significant differences in length of ICU stay according to mobilization initiation time. The results of this study indicate that initiation of mobilization within 48–72 h of mechanical ventilation may be optimal for improving clinical outcomes for mechanically ventilated patients.

Background DNA topoisomerase (Topo) inhibition plays key role in breast cancer treatment. Stephania hainanensis H. S. Lo et Y. Tsoong (S. hainanensis), a Li nationality plant that has abundant aporphine alkaloids, can inhibit Topo. Purpose To identify a dual Topo inhibitor, a deep and systematic study of active aporphine alkaloids in S. hainanensis and their mechanisms of inhibiting breast cancer proliferation and Topo activity are essential. Study design This study aimed to assess the anti-breast cancer and Topo inhibitory activities of oxocrebanine and explore the underlying mechanisms. Methods The growth inhibitory activities of 12 compounds in S. hainanensis were screened by MTT assay in MCF-7, SGC-7901, HepG-2 cells, and compared with the effects on human normal mammary epithelial MCF-10A cells as non cancer control cells. The Topo inhibitory activity was assessed by DNA relaxation and unwinding assays, kDNA decatenation assay and western blot. Cell cycle and autophagy analyses were carried out with flow cytometry and staining. Acridine orange staining and α-tubulin morphology were observed by fluorescence microscopy. Western blot was used to examine microtubule assembly dynamics and the expression levels of key proteins associated with DNA damage, autophagy and mitotic arrest. Results Oxocrebanine was the anti-breast cancer active alkaloid in S. hainanensis. It exhibited the best inhibitory effect on MCF-7 cells with an IC50 of 16.66 μmol/l, and had only weak effect on the proliferation of MCF-10A cells. Oxocrebanine inhibited Topo I and II α in a cell-free system and in MCF-7 cells. The DNA unwinding assay suggested that oxocrebanine intercalated with DNA as a catalytic inhibitor. Oxocrebanine regulated the levels of Topo I and IIα and DNA damage-related proteins. Oxocrebanine led to the mitotic arrest, and these effects occurred through both p53-dependent and p53-independent pathways. Oxocrebanine induced autophagy, abnormal α-tubulin morphology and stimulated enhanced microtubule dynamics. Conclusion Oxocrebanine was the anti-breast cancer active aporphine alkaloid in S. hainanensis. Oxocrebanine was a Topo I/IIα dual inhibitor, catalytic inhibitor and DNA intercalator. Oxocrebanine caused DNA damage, autophagy, and mitotic arrest in MCF-7 cells. Oxocrebanine also disrupted tubulin polymerization. Accordingly, oxocrebanine held a great potential for development as a novel dual Topo inhibitor for effective breast cancer treatment.

The bitter gourd (Momordica charantia L.) is a world-famous medical vegetable involved in multiple pharmacological activities especially known for its lipid- and glucose-lowering effects. As a result of its abundance of triterpenes and saponins (collectively called triterpenoids), growing evidence shows that they have a variety of biological effects, including anti-diabetic, anti-tumor, anti-bacterial, anti-viral, and anti-inflammatory activities. These studies indicate that triterpenoids (triterpenes) which are thought to play a key role in mediating diverse biological effects are likely to be underestimated in bitter gourd. To date, there is no comprehensive review specifying the composition and pharmacological activities of triterpenoids in this medical food. In this review, we focused on the structural diversity and biological function of M. charantia-derived triterpenes and saponins for the first time. The summarized information emphasizes the chemical complexity and promising clinical utility of M. charantia-derived triterpenoids which deserve more effort to be isolated, chemically characterized, functionally clarified, and eventually should be developed as new drugs or adjuvant treatment.

Lung cancer is a global disease and a major cause of cancer-related mortality worldwide. Accumulated studies have confirmed the essential role of long non-coding RNAs (lncRNAs) in the occurrence and development of cancers. Meanwhile, there have been reports concerning the role of Small Nucleolar RNA Host Gene 3 (SNHG3) in various cancers. However, there are so far few studies on the function and mechanism of SNHG3 in lung cancer. In the present study, SNHG3 was found to be highly expressed in lung cancer tissues and cells. Downregulation of SNHG3 could inhibit cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. In addition, SNHG3 was found to have the ability to bind to miR-515-5p. Furthermore, Small Ubiquitin Like Modifier 2 (SUMO2) was identified to be the downstream target of miR-515-5p, which was negatively correlated with miR-515-5p expression. SNHG3 could positively regulate SUMO2 expression by sponging miR-515-5p. In addition, the rescue experiment showed that simultaneous transfection of miR-515-5p or SUMO2 siRNA could reverse the effect of SNHG3 expression on cell proliferation and metastasis. Collectively, our study demonstrates that SNHG3 can act on miR-515-5p in the form of competitive endogenous RNA (ceRNA) to regulate SUMO2 positively and thus affect the proliferation and metastasis of NSCLC cells. Findings in our study support that SNHG3/miR-515-5p/SUMO2 regulatory axis may become a potential therapeutic target for lung cancer.

As one of the active pharmaceutical ingredients in Gamboge, Gambogenic acid (GNA) has shown diverse anti-tumor activities. To reduce the vascular irritation of GNA and improve its water solubility, tumor targeting, and bioavailability, GNA loaded Zein nanoparticles (GNA@Zein NPs) was further coated by polydopamine (PDA) to develop GNA@Zein-PDA NPs by anti-solvent precipitation and surface modification. The results showed that particle size and Zeta potential of GNA@Zein-PDA NPs were about 310 nm and −40.8 mV with core–shell morphology confirmed by TEM. GNA@Zein-PDA NPs increased the water solubility of GNA by more than 700 times and showed pH-sensitive release behavior in PBS with pH 6.86. In vitro cytotoxicity tests showed that GNA@Zein-PDA NPs had higher inhibitory activity on HepG2 cells than free GNA, and their IC50 were 1.59 μg/mL and 9.89 μg/mL, respectively. Additionally, the hemolysis and vascular irritation assay showed that GNA@Zein-PDA NPs had good cytocompatibility and reduced the irritation of GNA to blood vessels. Moreover, the in vivo pharmacokinetic experiments exhibited that the Cmax and AUC0-t of GNA@Zein-PDA NPs were significantly improved approximately by 2.09-fold and 3.48-fold over that of GNA, respectively. In conclusion, GNA@Zein-PDA NPs solve many defects of GNA and provide a tumor-targeting drug delivery for GNA.

A rapid, simple and reliable method using amoxicillin-D4 as internal standard (IS) for determination of amoxicillin (AMO) in porcine tissues was developed. The analytical methodology used a phosphate buffer (0.01 M, pH = 6.3) with trichloroacetic acid (50 mg/mL) for extraction and Oasis® HLB cartridges for clean-up followed by UPLC-MS/MS analysis. The optimized method was validated according to EU guideline 2002/657/EC and FDA guideline. The LOQ in muscle, fat, liver and kidney were set to 10 μg/kg which was below the maximum residue limits, while the LOD were set to 5 μg/kg. Results showed that using AMO-D4 as IS can effectively eliminate relative matrix interference and improve the recovery and precision. A good linearity was observed at the range of 10−500 μg/kg with a correlation coefficients (R2) larger than 0.99. The mean recoveries were higher than 87.0 %, and the RSDs were lower than 11.2 %. This method could be applied to conveniently analysis the residue of AMO in different porcine tissues.

Gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC), a newly identified lincRNA, was reported to be aberrantly expressed in several kinds of cancers and played an important role in tumor progression. This study was performed to systematically estimate the prognostic role of GAPLINC expression in cancer patients.Several electronic databases, including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for potential literature (updated to September 3, 2018). The pooled hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a fixed effects model using Stata12.0 software.The pooled results indicated that elevated GAPLINC was significantly related to shorter overall survival (OS) (HR = 1.66, 95%CI: 1.40-1.93, p0.001), which was further validated using The Cancer Genome Atlas (TCGA) dataset. Furthermore, high GAPLINC expression was correlated with higher tumor grade (OR = 1.91, 95%CI: 1.35-2.70, p0.001), positive lymph node metastasis (OR = 2.80, 95%CI: 1.69-4.64, p0.001), deeper infiltration depth (OR = 2.44, 95%CI: 1.43-4.17, p = 0.001) and advanced clinical stage (OR = 3.54, 95%CI: 2.13-5.88, p0.001).Our results suggest that elevated GAPLINC was associated with poor clinical outcomes and might serve as a promising prognostic biomarker in cancer survivors.

Supplemental Digital Content is available in the text, Background: Accumulating studies have indicated that Targeting protein for Xenopus kinesin-like protein 2 (TPX2) was overexpressed in various types of human cancers. However, the prognostic and clinical value of TPX2 in gastrointestinal (GI) tract cancers was not well-understood. This study was aimed to comprehensively explore the prognostic and clinical significance of TPX2 in GI tract cancers. Methods: Eligible studies were systematically retrieved in PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang database. The eligible studies were collected to evaluate the association of TPX2 with prognosis and clinicopathological features, with the pooling hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI). Result: The meta-analysis suggested that overexpression of TPX2 protein was significantly correlated with poor overall survival (OS) (HR: 2.20, 95% CI: 1.60–2.80, P

Objectives Resveratrol (Res), a naturally occurring polyphenol, has shown pharmacological activities in treatment of liver diseases. However, the application of Res was limited by its poor bioavailability and liver targeting. Herein, 3-O-β-D-Galactosylated Resveratrol (Gal-Res) was synthesized by structural modification of Res to enhance bioavailability and liver targeting. Methods The Gal-Res was characterized by IR, 1H-NMR spectra and MS. The in vitro antitumour experiments, in vivo pharmacokinetics and biodistribution studies were evaluated. Results Gal-Res was successfully synthesized in our study. Compared to Res, Gal-Res resulted in enhanced cytotoxicity in HepG2 cells. After intravenous injection of normal SD rats, Gal-Res significantly improved the bioavailability of Res and the Cmax and AUC0–t of Gal-Res were 3.186 and 3.929 time than that of Res. In addition, in the study of liver targeting, the relative uptake rate (Re) of Gal-Res in the liver (2.006) is the largest. The drug targeting efficiency (Te; 38.924%) of Gal-Res was greater than that of Res. These showed that Gal-Res could significantly improve the distribution ability of Res in liver. Conclusions On the whole, Gal-Res increased cellular uptake to HepG2 cells, bioavailability and liver targeting, providing its future clinical application in the treatment of liver diseases.

Purpose. The pathogenesis of chronic pulmonary aspergillosis (CPA) has seldom been studied due partly to a lack of animal models. Since hypha is the main morphology colonizing the airway in CPA, it’s critical to study the immune reaction to chronic pulmonary infection of hyphae of Aspergillus fumigatus, which also has seldom been studied in vivo before. Methodology. We established a novel murine model of chronic pulmonary infection of hyphae by challenging immunocompetent mice with tightly-structured hyphae balls intratracheally, and described the ensuing immunoreaction to hyphae and conidia, and the pathogenesis of CPA. Results. Our experiment proved that the hyphae balls could induce a chronic pulmonary infection for 28 days with a considerable recrudescence at day 28 post-infection. Lungs infected with hyphae balls were remarkable for the many neutrophils and macrophages that flooded into airway lumens, with peribronchiolar infiltration of leukocytes. There was a transient increase of Th2 cells and Th17 cells at day 7 post-infection in the lung tissue. In contrast, lungs infected with conidia showed no peribronchiolar infiltration of leukocytes, but an influx of a great number of macrophages, and a much less number of neutrophils in the lumen. Besides, conidia activated the co-response of Th1, Th2 and Th17 cells with an increase of Treg cells in the lung tissue (quite different from most previous studies). Conclusion. We established a new murine model of chronic infection of hyphae to mimic the formation of CPA, and provide a new marker for different immune responses to hyphae and conidia.

Wortmannin is an efficient inhibitor of phosphatidylinositol 3-kinases that is involved in normal plant growth. In this study, we performed the global proteomic analysis of the effects of wortmannin on wheat primary roots during seed germination. Wortmannin significantly inhibited the growth of wheat primary roots in a macroscopic level, and damaged the fine structure of nucleoli and mitochondria in a microscopic level. In total, 75 differentially accumulated protein (DAP) spots representing 66 unique DAPs were identified by linear two-dimensional electrophoresis and tandem mass spectrometry. These DAPs were mainly related to detoxification and defense response, carbon metabolism, and amino acid metabolism. Principal component analysis indicated that wortmannin significantly induced the proteomic changes between the treatment and control groups. Protein–protein interaction analysis revealed a complex network centralized by the 14-3-3 protein which was significantly upregulated in both transcriptional and translational levels. Furthermore, some key DAPs, such as heat shock-related proteins, glyceraldehyde-3-phosphate dehydrogenase, isocitrate dehydrogenase, 5-methyltetrahydropteroyltriglutamate–homocysteine methyltransferase, and elongation factor, also showed significantly upregulated accumulation, indicating their key roles in cell homeostasis maintenance, energy supply, and protein biosynthesis. Results obtained from this study provided a new insight into the molecular mechanism of wheat primary root in response to wortmannin during seed germination.

Background Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. The kinase ULK1 is required to activate this process. ULK1 phosphorylates a number of target proteins and regulates many cellular processes including the early secretory pathway. Recently, ULK1 has been demonstrated to phosphorylate Sec16 and affects the transport of serotonin transporter at the ER exit sites (ERES), but whether ULK1 may affect the transport of other cargo proteins and general secretion has not been fully addressed. Results In this study, we identified Sec23A, a component of the COPII vesicle coat, as a target of ULK1 phosphorylation. Elevated autophagy, induced by amino acid starvation, rapamycin, or overexpression of ULK1 caused aggregation of the ERES, a region of the ER dedicated for the budding of COPII vesicles. Transport of cargo proteins was also inhibited under these conditions and was retained at the ERES. ULK1 phosphorylation of Sec23A reduced the interaction between Sec23A and Sec31A. We identified serine 207, serine 312 and threonine 405 on Sec23A as ULK1 phosphorylation sites. Among these residues, serine 207, when changed to phospho-deficient and phospho-mimicking mutants, most faithfully recapitulated the above-mentioned effects of ULK1 phospho-regulation. Conclusion These findings identify Sec23A as a new target of ULK1 and uncover a mechanism of coordinating intracellular protein transport and autophagy. Electronic supplementary material The online version of this article (doi:10.1186/s12860-017-0138-8) contains supplementary material, which is available to authorized users.

Background Meta-analysis is often regarded as one of the best sources of evidence for clinical nurses due to its rigorous design and scientific reflection of the true results of nursing interventions. The quality of a meta-analysis is critical to the work of clinical decision-makers. Therefore, the objective of this study was to use the JBI guidelines to summarize the quality of RCT-based meta-analyses of reports published in domestic nursing professional journals, with a view to standardizing the research process and reporting methods. Methods We performed a comprehensive literature search for RCT-based meta-analyses published in Chinese professional nursing journals, from their inception to December 31, 2015, using bibliographic databases (e.g. CNKI, WanFang Database). March 1, 2017, supplementary search 2016 literature. Candidate reviews were assessed for inclusion by two independent reviewers using pre-specified eligibility criteria. We evaluated the quality of reporting of the included meta-analyses using the systematic review literature reporting specification of JBI. Analyses were performed using Excel and STATA 12.0 software. Results Three hundred and twenty-two meta-analyses were included. According to the JBI guidelines, the overall quality of the meta-analysis report was poor. The quality of core journal reports and the implementation of retrieval were better than those of non-core journals. The nature of the authors and the availability of funding support had no significant impact on the quality of the meta-analyses. Multi-unit and multi-author collaboration can help improve the quality of meta-analyses with significant impact. Conclusion The understanding and implementation of systematic evaluation and meta-analyses in domestic nursing professional journals is worthy of recognition, and there is more work that can be done to improve the quality of these reports. Systematic review / Meta-analysis (SR / MA) makers should include the findings of this study. Multi-institutional and multi-author collaborations appear to improve research capacity and provide more reliable evidence support for clinicians.

Mouse islets are widely used in diabetes research. Thus an adequate quality, quantity, and purity of islets are needed for high-quality investigations. We performed a combination of filtration and density gradient separation and optimized many steps in the islet isolation procedure, including perfusion, digestion, and purification. Our results show that an increased quality, quantity, and purity of isolated islets can be achieved using these modifications. Moreover, this method can guarantee maximal recovery and purity of the isolated islets and is easy to perform with practice.

OBJECTIVE To assess sexual activity, sexual function, and their correlation with vaginal maturation status among middle-aged Chinese women. METHODS A cross-sectional study with comparisons across age groups was carried out. In all, 120 women aged 45 to 60 years were recruited into three groups: 45 to 50 (youngest group), 51 to 55 (intermediate group), and 56 to 60 years old (eldest group). Sexual function was assessed through the Female Sexual Function Index (FSFI); vaginal maturation status was determined through the Vaginal Maturation Index (VMI) and pH value. Sexual activity was recorded with self-administered questionnaires. RESULTS Low sexual frequency was present in a higher proportion of women, but sexual distress was identified within a lower proportion of women in the eldest group. The total FSFI score was significantly lower in the eldest group than in the youngest and intermediate groups (P

Highlights • ALE meta-analysis reveals distributed brain networks for object and spatial functions in individuals with early blindness. • ALE contrast analysis reveals specific activations in the left cuneus and lingual gyrus for language function, suggesting a reverse hierarchical organization of the visual cortex for early blind individuals. • The findings contribute to visual rehabilitation in blind individuals by revealing the function-dependent and sensory-independent networks during nonvisual processing., Cross-modal occipital responses appear to be essential for nonvisual processing in individuals with early blindness. However, it is not clear whether the recruitment of occipital regions depends on functional domain or sensory modality. The current study utilized a coordinate-based meta-analysis to identify the distinct brain regions involved in the functional domains of object, spatial/motion, and language processing and the common brain regions involved in both auditory and tactile modalities in individuals with early blindness. Following the PRISMA guidelines, a total of 55 studies were included in the meta-analysis. The specific analyses revealed the brain regions that are consistently recruited for each function, such as the dorsal fronto-parietal network for spatial function and ventral occipito-temporal network for object function. This is consistent with the literature, suggesting that the two visual streams are preserved in early blind individuals. The contrast analyses found specific activations in the left cuneus and lingual gyrus for language function. This finding is novel and suggests a reverse hierarchical organization of the visual cortex for early blind individuals. The conjunction analyses found common activations in the right middle temporal gyrus, right precuneus and a left parieto-occipital region. Clinically, this work contributes to visual rehabilitation in early blind individuals by revealing the function-dependent and sensory-independent networks during nonvisual processing.