Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2'-deoxy-D-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.

Objective To investigate the clinical characteristics of paraneoplastic syndrome with prominent osteoarticular involvement. Methods The clinical materials of 20 patients with paraneoplastic syndrome with prominent osteoarticular involvement were collected. The characteristics of clinical manifest-ations, laboratory tests and imagines were analyzed. Results Among the 20 patients, 16 were male and 4 were female, with a mean age of 44.5 years and a median course of 6 months. Ten cases were associated with hematological tumor and 10 cases were associated with solid tumor. Eleven cases presented as peripheral arthritis (7 cases of polyarthritis, 4 cases of oligoarthritis/monoarthritis), 5 cases presented with hypertrophic osteoarthropathy (HOA) and 4 cases presented with tumor-induced osteomalacia (TIO). Three cases were acute lymphocytic leukemia, 2 cases were multiple myeloma, 1 case was lymphoma, and 1 case was bone tumor in polyarthritis. Four oligoarthritis cases were all associated with acute lymphocytic leukemia. All 5 cases of HOA were associated with lung cancer. All 4 cases of TIO were associated with tumor of mesenchymal tissue. Extra-articular manifestations presented in 14 cases and inflammatory markers increased in 15 cases. anti-cyclic cirullinated peptide (anti-CCP) antibodies was low titer positive in only 1 case and other parameters including rheumatoid factor (RF), anti-CCP antibodies, antinuclear antibodies spectrum (ANAs) and human leukocyte antigen (HLA)-B27 were negative. Multiple bone imaging abnormalities appeared in 15 cases. Conclusion Osteoarticular manifestations may be the first symptom of malignancy and difficult to diagnose. It is necessary to be highly aware of potential malignancy.

Objective To explore the current situation of family adaptability and cohesion of pa-tients with schizophrenia in China. Methods China National Knowledge Infrastructure ( CNKI),WanFang Database,VIP Database,CBM,PubMed and Cochrane library were searched from database established to Au-gust 15,2018. Case-control studies on family function in patients with schizophrenia were included and the published literatures were manually searched. Two researchers independently screened and extracted the in-cluded literatures and analyzed their family adaptability and cohesion using Review manager 5. 3 software. Results A total of 8 articles were included,including 678 in the study group and 780 in the control group. Meta-analysis results showed that the actual intimacy,actual adaptability and ideal adaptability of the study group were lower than the actual intimacy of the control group(WMD=-5. 13,95%CI(-7. 64--2. 62),P<0. 001),actual adaptability ( WMD=-4. 08,95% CI (-5. 63--2. 52), P<0. 001) and ideal adaptability ( WMD=-3. 50,95%CI(-6. 43--0. 57),P=0. 02),but there was no significant difference in the ideal inti-macy(WMD=-1. 10,95%CI(-4. 46-2. 25),P=0. 52);the unsatisfactory intimacy of the study group was higher than the control group(WMD=3. 07,95%CI (1. 78-4. 36),P<0. 001),but there was no significant difference in unsatisfactory adaptability(WMD=1. 51,95%CI(-0. 23-3. 24),P=0. 09). Conclusion The family intimacy and adaptability of patients with schizophrenia are at a low level,and social and family need to strengthen the attention of patients' family function.

Objective To assess the applicability of sound touch elastography ( ST E) and sound touch quantify ( ST Q ) in measuring liver and spleen stiffness . Methods One hundred and eighteen healthy volunteers were included and underwent ST E and ST Q . T he success rate ,variability and reproducibility of ST E and ST Q were analyzed . T he accurate sampling size and number of tests for liver ST Q were also analyzed . Results T he success rates ,variability ,reproducibility of ST E and ST Q in liver were 97 .5% and 99 .2% ,8 .7% and 12 .0% ,0 .917 and 0 .916 , respectively . While those with spleen were 76 .3% and 66 .9% ,12 .4% and 16 .4% ,0 .847 and 0 .706 ,respectively . The sampling size of 1 .5 cm×1 .0 cm yield the lowest variability ( 8 .5% ) ( F ＝6 .562 , P ＝0 .002) ,and there was no significant difference between results of detecting 5 times and 10 times( P ＝0 .571) . T he liver and spleen stiffness of ST E were 5 .75 kPa ( 95%CI :5 .60－5 .91 kPa) and 15 .58 kPa ( 95% CI :14 .99 －16 .16 kPa) . Conclusions The measurement of liver stiffness using both ST E and ST Q have a high success rate and low variability . However ,ST E is better than STQ in measuring spleen stiffness .

Objective: To investigate the effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on apoptosis and proliferation of human lung adenocarcinoma A549 cells via PI3K/AKT signaling pathway, and to explore the mechanism. Methods: UCMSCs were isolated from human umbilical cord tissues by enzyme digestion method and cultured in vitro. The immunophenotypes of the obtained MSCs were identified by flow cytometry. The culture supernatant of UC-MSCs was collected to establish an indirect in vitro co-culture system of UC-MSCs conditioned medium and lung adenocarcinomaA549 cell line. Proliferation ofA549 cells was detected by CCK-8 assay; apoptosis ofA549 cells was determined byAnnexin V/PI double staining, and cell cycle distribution of tumor cells was determined by PI staining. The transcription levels of apoptosis and proliferation associated downstream genes in the PI3K/AKT pathway, such as CyclinD1, BAX and Bcl-2, were detected by quantitative polymerase chain reaction (qPCR). Moreover, Wb was utilized to detect the expression levels of PI3K/AKT pathway-related proteins. Results: The culture flask was filled with fibroblast-like cells, arranged in parallel, with spiral growth after three weeks of isolation and culture of human umbilical cord tissues. The flow cytometry results revealed that the MSC markers CD73, CD90 and CD105, but not CD45 and HLA-DR, were expressed on obtained cells.After indirect in vitro co-culture of UC-MSCs conditioned medium and lung adenocarcinoma A549 cells, the proliferation rate of A549 cells was significantly decreased; the apoptosis rate was significantly increased, and the cell cycle was obviously arrested at the G1 phase as compared with the control group (all P<0.01). The transcription levels of PI3K/AKT signaling pathway-related factors, CyclinD1 and Bcl-2 were down-regulated, and the transcription level of BAX was up-regulated (all P<0.01). The total AKT was not changed, but p-AKT protein expression was decreased in a dose-dependent manner inA549 cells cultured in UC-MSCs conditioned medium (P<0.01). Conclusion: UC-MSCs can affect the proliferation and the apoptosis of A549 cells, and arrest cells in G1 phase. The main mechanism is that UC-MSCs can inhibit the PI3K/AKT signaling pathway in A549 cells, providing an experimental basis for exploring the safety and effectiveness of clinical application of UC-MSCs.

Acceptance and Commitment Therapy (ACT) aims at correctly recognizing the different sides of life, accepting its inevitable pain, defining its true value and committing to action.Its ultimately aim is to improve psychological flexibility and lead a more fulfilling and meaningful life.Patients with Eating Disorders (ED) often have personality characteristics such as experiential avoidance, rigid behavior, and lack of motivation.Therefore, Acceptance and Commitment Therapy is particularly suitable for patients with Eating Disorders.This article make a brief overview of the ACT firstly, then introduces the definition, epidemiology and etiology of ED.By reviewing the relevant literatures on the use of ACT in the treatment of ED in recent years, we point out the advantages of using ACT and the possible mechanism of ACT in the treatment of ED, the future research directions and issues needing attention.

Objective To analyze the efficacy and safety of erlotinib associated conformal intensity modulated radiotherapy in treatment (IMRT) of locally advanced pancreatic carcinoma. Methods The clinical data of 23 patients with locally advanced pancreatic carcinoma were retrospectively analyzed. The patients′ therapeutic methods: erlotinib was taken continuously and orally at 100 mg/time, 1 time/d until disease progressed or serious adverse reactions happened; intensity modulated radiotherapy (IMRT) was used combined with erlotinib at 50.4 Gy, 1 time/d, 1.8 Gy/time, 5 times/week, total 28 times. Tumor response was evaluated at the end of radiotherapy after 4 weeks. Results In 23 patients, there was partial response in 10 cases, stable disease in 9 cases and progress disease in 4 cases. The objective response rate was 43.5%(10/23), and the median survival time was 11.3 months. Adverse reactions included fatigue, rash, bone marrow suppression, nausea and diarrhea. The adverse reactions were mostly tolerable with grade 1-2. Conclusions Erlotinib combined with IMRT is safe and effective in patients with locally advanced pancreatic carcinoma, which is worthy of further study.

Objective To investigate the feasibility and efficacy of the intensity modulated radiotherapy (IMRT) with oral S-1 for locally advanced pancreatic cancer.Methods Forty-two patients with locally advanced pancreatic cancer were selected,and the patients were divided into 2 groups by random digits table method with 21 cases each.The patients in treatment group were treated by IMRT combined with oral S-1 40 mg/m2 twice daily from day 1 to day 14 of a 21-d cycle;the patients in control group were treated by IMRT combined with 30 min intravenous infusions of gemcitabine 1 000 mg/m2 on day 1,8,21 and 29.Radiation was concurrently delivered at a dose of 50.4 Gy (1.8 Gy/d,5 times per week,28 fractions).The dose of intensity modulated radiotherapy was 1.8 Gy/time (5 times/week,50.4 Gy/28 times).The recent curative effect and untoward reaction were assessed at the end of radiotherapy after 4 weeks.Results There were no statistical differences in efficient rate and disease control rate between treatment group and control group:57.1％ (12/21) vs.47.6％ (10/21) and 85.7％ (18/21) vs.76.2％ (16/21),P ＞ 0.05.The neutropenia rate and thrombocytopenia rate in treatment were significantly lower than those in control group:23.8％ (5/21) vs.57.1％ (12/21) and 28.6％ (6/21) vs.66.7％ (14/21),and there were statistical differences (P ＜ 0.05).There were no statistical differences in the incidences of anemia,nausea,vomiting,elevated aminotransferase and fatigue (P＞ 0.05).Conclusions The IMRT with oral S-1 for locally advanced pancreatic cancer is safe and effective.It is worthy of clinical promotion.

We observed the influence of methanol concentration on purification recovery of recombinant human consensus interferon-a (cIFN) produced by Pichia pastoris. Fermentations controlled at 0.75% (W/V) methanol showed a 24% increase in clFN expression compared to using 0.25% methanol. However, the purification recovery rate of cIFN at 0.25% methanol was 3.75-fold higher than that at 0.75% methanol. To seek the reason, we analyzed the stability of clFN by SDS-PAGE and Native-PAGE as well as Western blotting. The electrophoresis results revealed that cIFN formed a lot of aggregates in media when the induction was controlled at 0.75% methanol, and two different aggregate forms were found: disulfide bond covalent aggregates and non-covalent aggregates. However, these aggregates almost disappeared when the methanol concentration was controlled at 0.25%, at the same time, cIFN bioactivity of supernatant increased almost 4.48-fold. Finally, 0.73g monomer cIFN was obtained after purification from 1 liter supernatant at 0.25% methanol induction, showed a 2.84-fold increase compare to the induction at 0.75% methanol.
Antiviral Agents ; isolation & purification ; Fermentation ; Humans ; Interferon-alpha ; biosynthesis ; genetics ; isolation & purification ; Methanol ; analysis ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification