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Objective: To observe the clinical effect of Tongdu Tiaoshen acupuncture on chronic insomnia, and explore its possible mechanism., Methods: A total of 60 patients with chronic insomnia were randomly divided into an observation group (30 cases) and a control group (30 cases, 1 case dropped off ). The observation group was treated with Tongdu Tiaoshen acupuncture at Baihui (GV 20), Yintang (GV 29), Shenting (GV 24), etc. once every other day, 3 times a week. The control group was treated with estazolam tablets (1 mg) orally before going to bed every night. The treatments of both groups were required 4 weeks. The Pittsburgh sleep quality index (PSQI) scores, serum gamma-aminobutyric acid (GABA) and cortisol (CORT) levels were observed before and after treatment in the two groups, and the clinical effect was compared., Results: After treatment, the sleep quality, day dysfunction scores of PSQI in the observation group and the falling asleep time, sleep time, sleep efficiency, sleep disturbance scores and total scores of PSQI in the two groups were lower than before treatment ( P <0.01, P <0.05). After treatment, the daytime dysfunction score of PSQI in the observation group was lower than that in the control group ( P <0.05). After treatment, the serum GABA levels in the two groups were higher than before treatment ( P <0.05), and the serum CORT levels were lower than before treatment ( P <0.01). The total effective rate was 90% (27/30) in the observation group and 93.1% (27/29) in the control group, the difference was not statistically significant ( P >0.05)., Conclusion: Tongdu Tiaoshen acupuncture has the same effect as western medication estazolam tablets in the treatment of patients with chronic insomnia, and has little effect on daytime dysfunction. The mechanism may be related to the increase of serum GABA level and the inhibition of the hyperactivation of hypothalamus-pituitary-adrenal (HPA) axis.

Foresight of CO 2 emissions from fuel combustion is essential for policy-makers to identify ready targets for effective reduction plans and to further improve energy policies and plans. A new method for forecasting the future development of China's CO 2 emissions from fuel combustion is proposed in this paper by using grey forecasting theory. Although the existing fractional nonlinear grey Bernoulli model (denoted as FNGBM(1,1)) has been theoretically proven to enhance the adaptability to diverse sequences, its fixed integer-order differential derivative still impairs the performance to some extent. To this end, a varying-order differential derivative is introduced into the existing differential equation to enable a more flexible structure, thus improving the prediction ability of FNGBM(1,1). Specifically, because of the advantages of conformable fractional accumulation, the traditional differential derivative is first replaced by the conformable fractional differential derivative. As a consequence, the continuous conformable fractional nonlinear grey Bernoulli model (hereinafter referred to as CCFNGBM(1,1)) is proposed. To further increase the validity of the model, a metaheuristic algorithm, namely Grey Wolf Optimizer (GWO), is then applied to search for the optimal emerging coefficients for the proposed model. Two real examples and China's CO 2 emissions from fuel combustion are considered to verify the effectiveness of the newly proposed model, the experimental results show that the newly proposed model outperforms other benchmark models in terms of forecasting accuracy. The proposed model is finally employed to forecast the future China's CO 2 emissions from fuel combustion by 2023, accounting for 10,039.80 million tons. Based on the forecasts, several policy suggestions are provided to curb CO 2 emissions., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism., Methods: A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected., Results: After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment ( P <0.01, P <0.05), among them, the sub-item scores of sleep quality, time to fall asleep, sleep time and sleep efficiency, daytime dysfunction and total score were all lower than those in the sham EA group ( P <0.01, P <0.05). After treatment, the MoCA score and serum MT and DA levels in the EA group were higher than those before treatment ( P <0.01), and the MoCA score and serum MT level in the EA group were higher than the sham EA group ( P <0.01, P <0.05)., Conclusion: Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.

The application of pit and fissure sealants is a well-established method to prevent and treat early childhood caries. Resin-based sealants with antibacterial properties provide additional benefits for caries prevention in a cariogenic oral environment. The objective of this study was to evaluate the effect of an antibacterial core-shell AgBr/cationic polymer nanocomposite (AgBr/BHPVP) on the properties of a resin-based pit and fissure sealant. A commercialized pit and fissure sealant without fluoride, Concise (3M, ESPE, USA), was used as the parent material and negative control. Experimental antibacterial sealants were formulated by the addition of AgBr/BHPVP nanoparticles at mass fractions of 0.5, 1.0, and 1.5 wt% to the parent material. A fluoride-releasing sealant, Clinpro (3M, ESPE), was used as the positive control. Bacterial colony-forming unit (CFU) counts, metabolic activity tests, field emission-scanning electron microscopy (FE-SEM), and confocal laser scanning microscopy (CLSM) observations were used to evaluate the antibacterial properties of AgBr/BHPVP-modified sealants against Streptococcus mutans before and after five months of aging. The Vickers microhardness, degree of conversion, and microleakage level of the sealants were also investigated. According to the results of CFU counts and metabolic tests, sealants containing AgBr/BHPVP showed better contact-killing bactericidal activity against S. mutans than the two commercial sealants, irrespective of aging conditions (both P < 0.05). The AgBr/BHPVP-modified sealants also showed a significant inhibitory effect on the planktonic S. mutans around the cured sealant surfaces. In addition, the Vickers microhardness, degree of conversion, and microleakage level of the parent material were not damaged by modification with AgBr/BHPVP (P > 0.05). AgBr/BHPVP-modified pit and fissure sealant with a dual bactericidal mechanism is a promising option for the prevention of pit and fissure caries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Many women with perimenopausal insomnia (PMI) have sought alternative therapies such as acupuncture because of concerns about risks associated with hormone replacement therapy (HRT) and/or psychotropic drugs. This systematic review aimed to clarify if acupuncture alone or combined with standard Western pharmacotherapy (HRT and/or psychotropic drugs) is more effective in ameliorating PMI in comparison to pharmacotherapy alone., Methods: Randomized controlled trials (RCTs) of PMI treatment via acupuncture alone or combined with Western pharmacotherapy versus Western pharmacotherapy were searched for from eleven databases from inception to March 2020. Cochrane criteria were followed., Results: Fifteen studies involving 1410 women were analyzed. Meta-analysis indicated that acupuncture significantly reduced the global scores of Pittsburgh Sleep Quality Index (PSQI) [MD = -2.38, 95% CI (-3.38, -1.37), p  < 0.01] and Kupperman Index [MD = -5.95, 95% CI (-10.68, -1.21), p  = 0.01], compared with hypnotics. Acupuncture combined with hypnotics was more effective than hypnotics alone in decreasing PSQI scores [MD = -3.13, 95% CI (-5.43, -0.83), p  < 0.01]. Too few RCTs were available to investigate the clinical efficacy differences between acupuncture and HRT/psychotropic drugs other than hypnotics., Conclusions: Despite limited evidence, in comparison to hypnotics, acupuncture was associated with significant improvements in PMI, and reductions of other menopausal symptoms. This finding suggests that acupuncture may be a useful addition to treatment for PMI., Competing Interests: None of the authors have any conflicts of interest to declare in this study., (Copyright © 2021 Fei-Yi Zhao et al.)

Background: The efficacy of acupuncture for treating primary insomnia (PI) has been explored in several meta-analyses where the outcomes measures were based on subjective self-reported sleep rating scales. Sleep state misperception is common in PI and self-reports underestimate sleep duration and quality. No systematic reviews or meta-analyses have investigated the efficacy of acupuncture in improving objective sleep measures in PI., Objective: To perform a systematic review to determine whether objective sleep parameters are improved by acupuncture in patients with PI., Methods: Randomized controlled trials treating PI via verum-acupuncture versus sham-/placebo-acupuncture or waitlist control were searched for in English [MEDLINE (via PubMed), Sciverse ScienceDirect, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, Springer, EMBASE (Elsevier), Ebsco Medline, and PsycINFO (ProQuest)] and Chinese (SinoMed, CNKI, Wanfang and CQVIP) databases, from the dates of the databases' inception to January 2020. The parameters of polysomnography (PSG), actigraphy, or micromovement sensitive mattress/pillow sleep monitoring systems were considered as the primary outcome measures. Revman 5.3 and Stata 16.0 software were used to conduct the meta-analysis. Heterogeneity was examined by using I 2 statistics and publication bias was assessed via Egger's test., Results: Eleven studies involving 775 patients met the inclusion criteria. The results of meta-analysis suggested that acupuncture can increase total sleep time [MD = 55.29, 95%CI (29.16, 81.42), p < 0.01], increase sleep efficiency [MD = 8.96, 95%CI (3.97, 13.95), p < 0.01], decrease wake after sleep onset [MD = -49.54, 95%CI (-82.98, -16.09), p < 0.01], and reduce number of awakening times [MD = -6.29, 95%CI (-10.75, -1.82), p < 0.01] compared with either sham-/placebo-acupuncture or waitlist control. Subsequent analysis indicated a superior effect for verum-acupuncture in comparison with sham-/placebo-acupuncture or waitlist-control when the recommended lowest threshold dosage (12 sessions) was met. Despite positive outcomes, most studies reviewed were heterogeneous and at risk of bias due to methodological issues., Conclusions: Despite limited evidence, acupuncture was significantly associated with improvements in several objective sleep parameters (increases in total sleep time and sleep efficiency, and reductions in wake after sleep onset and number of awakening times) as well as subjective sleep quantity and quality in patients with PI. A minimum therapeutic threshold dosage (≥12 sessions) is recommended. Well-designed RCTs using PSG are required to clarify the influence of acupuncture on sleep architecture/structure and to promote better application of acupuncture as a treatment for PI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dentin bonding is a dynamic process that involves the penetration of adhesive resin monomers into the extrafibrillar and intrafibrillar demineralized collagen matrix using a wet-bonding technique. However, adhesive resin monomers lack the capacity to infiltrate the intrafibrillar space, and the excess water that is introduced by the wet-bonding technique remains at the bonding interface. This imperfectly bonded interface is inclined to hydrolytic degradation, severely jeopardizing the longevity of bonded clinical restorations. The present study introduces a dentin bonding scheme based on a dry-bonding technique, combined with the use of extrafibrillar demineralization and a collagen-reactive monomer (CRM)-based adhesive (CBA). Selective extrafibrillar demineralization was achieved using 1-wt% high-molecular weight (MW) carboxymethyl chitosan (CMCS) within a clinically acceptable timeframe to create a less aggressive bonding substance for dentin bonding due to its selectively extrafibrillar demineralization capacity. CMCS demineralization decreased the activation of in situ collagenase, improved the shrinking resistance of demineralized collagen, and thus provided stronger and more durable bonding than traditional phosphoric acid etching. The new dentin bonding scheme that contained CMCS and CBA and used a dry-bonding technique achieved an encouraging dentin bonding strength and durability with low technical sensitivity. This bonding scheme can be used to improve the stability of the resin-dentin interface and foster the longevity of bonded clinical restorations., Competing Interests: The authors declare no competing interest., (© 2021 The Authors.)

Objective: To observe the clinical effect of acupuncture at Tiaoshen (regulating the spirit) acupoints on chronic insomnia and hyperarousal state, and explore its possible mechanism., Methods: A total of 60 patients with chronic insomnia were randomly divided into an acupuncture group (30 cases, 1 case dropped off) and a sham acupuncture group (30 cases, 1 cases dropped off). Both groups were given basic sleep health education. The acupuncture group was treated with acupuncture at Tiaoshen acupoints including Baihui (GV 20), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7) and Sanyinjiao (SP 6). The sham acupuncture group was treated with non-effective point shallow acupuncture. Both groups were treated once every other day, 3 times a week for 4 weeks. The Pittsburgh sleep quality index (PSQI) score, pre-sleep arousal scale (PSAS) score, hyperarousal scale (HAS) score, and serum gamma-aminobutyric acid (GABA) level before and after treatment were compared between the two groups., Results: Compared before treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group after treatment were decreased ( P <0.05, P <0.01); in the sham acupuncture group, the time to fall asleep, daytime dysfunction scores and total score of PSQI, and cognitive arousal score of PSAS after treatment were decreased ( P <0.05). After treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group were lower than those in the sham acupuncture group ( P <0.05, P <0.01). Compared before treatment, the serum GABA level in the acupuncture group were increased ( P <0.05), and the serum GABA level in the acupuncture group was higher than that in the sham acupuncture group after treatment ( P <0.05)., Conclusion: Acupuncture at Tiaoshen acupoints can obviously improve the sleep and hyperarousal state of patients with chronic insomnia, and up-regulating serum GABA content is one of its possible mechanisms.

BACKGROUND Hepatocellular carcinoma (HCC) causes a heavy disease burden worldwide. Cell division cycle 45 (Cdc45) and its encoding gene (CDC45) have been studied for a long time, but their expression patterns and roles in liver carcinogenesis and advanced HCC deterioration are still incompletely understood. This study integrated tissue microarray and bioinformatics analyses to explore the expression and clinical value of CDC45 and Cdc45 in HCC. MATERIAL AND METHODS In HCC, the expression and relationships with clinic-pathological parameters of CDC45 and Cdc45 were investigated by integrating the RNA-sequencing data, downloaded from The Cancer Genome Atlas and Oncomine databases, and tissue microarray with immunohistochemistry staining. Co-expressed genes and genetic alterations of CDC45 separately obtained from Oncomine and cBioPortal databases were identified to shed light on the potential mechanisms of CDC45 in HCC. RESULTS CDC45 and Cdc45 were both overexpressed in HCC tissues, and the CDC45 level progressively increased from stage I to III. The survival outcomes of the group with high CDC45 expression were significantly worse compared with the group with low expression. Amplification and deep deletion were 2 major significant alteration types in HCC patients, and the outcomes were worse in patients with altered versus unaltered CDC45. NUDT1, E2F1, CCNE2, MCM5, and CENPM were identified as the most significantly co-expressed genes. CONCLUSIONS CDC45 and Cdc45 were both upregulated in HCC, and increased expression levels and genetic alternations of CDC45 were correlated with worse prognosis in HCC patients. CDC45 may promote HCC by co-expressing with NUDT1, E2F1, CCNE2, MCM5, and CENPM.

Objective: To compare the clinical therapeutic effect and safety on insomnia among three acupuncture combinations, named Tongdu Tiaowei (promoting the circulation of the governor vessel and regulating the defensive system), Tongdu Yangxin (promoting the circulation of the governor vessel and nourishing the heart) and Tongdu Tiaozang (promoting the circulation of the governor vessel and regulating zang functions)., Methods: A total of 90 patients with insomnia were randomized into a Tongdu Tiaowei group (30 cases, 1 case dropped off ), a Tongdu Yangxin group (30 cases, 2 cases dropped off ) and a Tongdu Tiaozang group (30 cases, 1 case dropped off ). Besides electroacupuncture (EA) applied to Baihui (GV 20) and Yintang (GV 29) in all of the three groups, acupuncture was added at Shenmai (BL 62) and Zhaohai (KI 6), Shenmen (HT 7) and Sanyinjiao (SP 6) as well as back- shu points of five zang organs [Feishu (BL 13), Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20) and Shenshu (BL 23)] in the Tongdu Tiaowei group, the Tongdu Yangxin group and the Tongdu Tiaozang group successively. The treatment was given once every two days, 3 times weekly, consecutively for 4 weeks. The score of Pittsburgh sleep quality index (PSQI) before and after treatment was observed, the therapeutic effect was evaluated and the adverse reactions were recorded in the patients of each group., Results: After treatment, the score of each of 6 factors, named sleep quality, sleep latency, sleep time, sleep efficiency, sleep disturbance and daytime dysfunction, as well as the total score of PSQI scale were all reduced as compared with the scores before treatment in the patients of each group ( P <0.05). After treatment, the scores of sleep latency and daytime dysfunction in the Tongdu Tiaowei group were lower than the other two groups ( P <0.05). The score of sleep time in the Tongdu Yangxin group was lower than the other two groups ( P <0.05) and the score of sleep quality in the Tongdu Tiaozang group was lower than the other two groups ( P <0.05). After treatment, the total effective rates were 96.6% (28/29), 96.4% (27/28) and 96.6% (28/29) in the Tongdu Tiaowei group, the Tongdu Yangxin group and the Tongdu Tiaozang group successively, without significant difference in comparison among the three groups ( P >0.05). During treatment, 1 case of mild adverse reaction occurred in each group., Conclusion: All of the three acupuncture combinations, named Tongdu Tiaowei , Tongdu Yangxin and Tongdu Tiaozang can effectively improve the sleep conditions in the patients with insomnia and are satisfactory in safety. The acupuncture combinations of Tongdu Tiaowei has the potential advantage in shortening sleep latency and relieving daytime dysfunction, the combinations of Tongdu Yangxin has the potential advantage in increasing sleep time and the combinations of Tongdu Tiaozang has the potential advantage in improving sleep quality.

Epithelial-mesenchymal transition (EMT), a pivotal event during cancer progression such as relapse and metastasis, is positively correlated with the stemness potency of tumor cells. Our previous study showed that miR-296-5p attenuated EMT program of hepatocellular carcinoma cells (HCC) through NRG1/ERBB2/ERBB3 signaling. In the present study, we uncovered that miR-296-5p was able to inhibit the stemness potency of HCC by decreasing the number and size of tumorspheres, downregulating the expression of CSC biomarkers and hampering the ability of tumorigenesis in NOD/SCID mice. Brahma-related gene-1 (Brg1), as the target protein of miR-296-5p detected by bioinformatics methods, activates a series of downstream cascades through directly binding to Sall4 promoter and enhancing Sall4 transcription. Importantly, the higher expressions of Brg1 and Sall4 in tumor tissues of HCC patients suggest poorer prognoses after surgical extraction. In conclusion, miR-296-5p exerts an inhibitory effect on stemness potency of HCC cells via Brg1/Sall4 axis., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study is to come up with new methods to quantitate the blood loss under endoscope and explore the influence of blood loss on percutaneous endoscopic lumbar discectomy (PELD)., Methods: Clinical research and in vitro experiment are combined. In the in vitro experiment, 2.0-ml blood was diluted in different ratio to simulate the rinse solution of PELD, the hematocrit method (HCT-M) and red blood cell count method (RBC-M) were came up to estimate blood loss and the new methods were calibrated with the direct measurement method (Direct-M). In clinical research, 74 patients with L5/S1 disk herniation were treated with PELD, and HCT-M and the empirical method (EMP-M) were used to estimate the blood loss under endoscope. According to blood loss, all patients were divided into group A (≤ 10 ml) and group B (> 10 ml). The blood loss, operation time, fluoroscopy frequency, visual analog scale (VAS), and Oswestry Disability Index (ODI) scores were compared between the two groups., Results: In the in vitro experiment, the hematocrit of the rinse solution was always stable over time. The estimated blood loss by HCT-M was stable and quite approximate to actual blood volume (2.0 ml) whatever the blood dilution ratio, while according to RBC-M, the estimated blood loss was close to the actual blood volume only when the dilution ratio was greater than 300 times. In clinical research, the blood loss estimated by HCT-M was higher than that by EMP-M in both groups (P < 0.05). There was a significant difference between group A and group B in blood loss (7.40 ± 1.61 vs 19.91 ± 10.94 ml), operation time (80.51 ± 34.70 vs 136.51 ± 41.88 min), and fluoroscopy frequency (6.92 ± 1.52 vs 11.11 ± 2.32 times) (P < 0.05). The VAS and ODI scores in group B were higher than that in group A 1 week after operation (P < 0.05); however, the scores were not different between the two groups at pre-operation (P > 0.05)., Conclusion: HCT-M is a reliable method to estimate endoscopic blood loss in PELD. The amount of endoscopic blood loss affects the operative procedure in operation time and fluoroscopy frequency, as well as clinical effects in VAS and ODI scores after operation in short term.

Objective: To investigate the clinical effect of Tongdu Tiaoshen needling in the treatment of chronic insomnia and its mechanism based on the hypothalamic-pituitary-adrenal (HPA) axis., Methods: A total of 60 patients with chronic insomnia were randomly divided into treatment group and control group, with 30 patients in each group. In addition to the health education on sleep, the patients in the treatment group were given Tongdu Tiaoshen needling, i．e., electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (EX-HN3), bilateral Shenmen (HT7), and bilateral Sanyinjiao (SP6), and those in the control group were given superficial acupuncture at Shousanli (LI10), Futu (ST32), and Feiyang (BL58) at both sides, once every other day and three times a week for 4 consecutive weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) was used to assess the quality and efficiency of sleep, and ELISA was used to measure the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT)., Results: After treatment, the treatment group had significant reductions in the total PSQI score and the score of each component of PSQI ( P <0.01), and the control group had significant reductions in the total PSQI score ( P <0.01) and the scores of all components except sleep duration ( P <0.05); compared with the control group, the treatment group had significantly lower total PSQI score and the score of each component ( P <0.01). After treatment, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT ( P <0.05，P <0.01), and compared with the control group, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT ( P <0.01， P <0.05)., Conclusion: Tongdu Tiaoshen needling has a good clinical effect in the treatment of chronic insomnia and can significantly improve the sleep condition of patients with chronic insomnia, possibly by reducing the hormones associated with the HPA axis.

An amendment to this paper has been published and can be accessed via the original article.

Objective: Acute lymphoblastic leukemia (ALL) causes the dysfunction of the systemic blood system and immune system. The etiology and predisposing factors of ALL are unknown. The suppressor of cytokine signaling 1 (SOCS1) and SOCS2 are inhibitors of cytokine signal transduction. Gene polymorphisms of SOCS1 and SOCS2 and their expressions may be related to ALL., Patients and Methods: A total of 200 ALL patients in our hospital and 200 healthy people were enrolled in ALL group and control group, respectively. Genomic deoxyribonucleic acids (DNAs) and total RNAs were extracted from the peripheral blood of each subject. Gene polymorphisms of SOCS1 at rs33977706, rs243327, and rs33932899 and those of SOCS2 at rs3816997 were amplified by polymerase chain reaction (PCR) and sequenced. Besides, the expression levels of SOCS1 and SOCS2 in ALL patients were detected by real-time fluorescence quantitative PCR., Results: The frequency of the allele C of SOCS1 rs33977706 in ALL group was lower than that in the control group, displaying a significant difference between the two groups (p=0.015). The frequency of allele A of SOCS2 rs3816997 was notably higher in ALL group than that of the control group (p=0.000). In addition, the frequency of CA genotype of SOCS1 rs33977706 in ALL group was markedly lower than that in the control group, showing a significant difference (p=0.000). ALL group had remarkably higher frequencies of AA genotype of SOCS2 rs3816997 (p=0.000) and ACC haplotype of SOCS gene (p=0.000), and lower frequencies of ATG (p=0.026) and CCC (p=0.006) haplotypes. The two loci, SOCS1 rs33932899 and SOCS1 rs243327, were linked to each other (D'=0.781). Moreover, the expression level of SOCS1 in ALL group was lower than that in the control group, in which the expression of the CT genotype of SOCS1 rs243327 was relatively higher (p=0.021). SOCS2 level was lower in ALL group. Particularly, SOCS2 level in ALL patients carrying AC genotype was lower than those carrying AA and CC genotypes (p=0.000). ALL patients carrying CT genotype of SOCS1 rs243327 had shorter period of agranulocytosis (p=0.000), a lower ratio of bone marrow primitive/immature cells (p=0.001), and a higher hemoglobin (Hb) level in blood (p=0.000). The ratio of bone marrow primordial/immature cells was lower in ALL patients with AC genotype of SOCS2 rs3816997 (p=0.038)., Conclusions: The expression levels of SOCS1 and SOCS2 are prominently related to ALL, and their polymorphisms are associated with the susceptibility to ALL.

Dysregulation of microRNA (miRNA) is a frequent event in hepatocellular carcinoma (HCC), but little is known whether it is a bystander or an actual player on residual HCC metastasis during liver microenvironment remodeling initiated by hepatectomy. Methods: The differently expressed miRNAs and mRNAs were identified from RNA-seq data. Western blot, qRT-PCR, fluorescence in situ hybridization, immunofluorescence and immunohistochemical were used to detect the expression of miRNA and mRNA in cell lines and patient tissues. The biological functions were investigated in vitro and in vivo . Chromatin immunoprecipitation, proximity ligation and luciferase reporter assay were used to explore the specific binding of target genes. The expression of HGF/ERBB3 signaling was detected by Western blot. Results: In this study, HGF induced by hepatectomy was shown to promote metastasis of residual HCC cells. miR-17-5p and miR-20a-5p were confirmed to play inhibitory roles on HCC metastasis. And ERBB3 was found to be the common target of miR-17-5p and miR-20a-5p. HCC cells with lower levels of miR-17-5p and miR-20a-5p or higher level of ERBB3 were often more sensitive to response HGF stimuli and to facilitate metastatic colonization both in vitro and in vivo experimental systems. Furthermore, HGF reinforced ERBB3 expression by NF-κB transcriptional activity in a positive feedback loop. Of particular importance, HCC patients with lower levels of miR-17-5p and miR-20a-5p or higher level of ERBB3 had significantly shorter OS and PFS survivals after surgical resection. Conclusion: miR-17-5p and miR-20a-5p could suppress postoperative metastasis of hepatocellular carcinoma via blocking HGF/ERBB3-NF-κB positive feedback loop and offer a new probable strategy for metastasis prevention after HCC resection., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: MicroRNA-612 (miR-612) has been proven to suppress EMT, stemness, and tumor metastasis of hepatocellular carcinoma (HCC) via PI3K/AKT2 and Sp1/Nanog signaling. However, its biological roles on HCC progression are far from elucidated., Methods: We found direct downstream target of miR-612, hadha by RNA immunoprecipitation and sequencing. To explore its biological characteristic, potential molecular mechanism, and clinical relevance in HCC patients, we performed several in-vitro and in-vivo models, as well as human tissue chip., Results: Ectopic expression of miR-612 could partially reverse the level of HADHA, then suppress function of pseudopods, and diminish metastatic and invasive potential of HCC by lipid reprogramming. In detail, miR-612 might reduce invadopodia formation via HADHA-mediated cell membrane cholesterol alteration and accompanied with the inhibition of Wnt/β-catenin regulated EMT occurrence. Our results showed that the maximum oxygen consumption rates (OCR) of HCCLM3 miR-612-OE and HCCLM3 hadha-KD cells were decreased nearly by 40% and 60% of their counterparts (p < 0.05). The levels of acetyl CoA were significantly decreased, about 1/3 (p > 0.05) or 1/2 (p < 0.05) of their controls, in exogenous miR-612 or hadha-shRNA transfected HCCLM3 cell lines. Besides, overexpression of hadha cell lines had a high expression level of total cholesterol, especially 27-hydroxycholesterol (p < 0.005). SREBP2 protein expression level as well as its downstream targets, HMGCS1, HMGCR, MVD, SQLE were all deregulated by HADHA. Meanwhile, the ATP levels were reduced to 1/2 and 1/4 in HCCLM3 miR-612-OE (p < 0.05) and HCCLM3 hadha-KD (p < 0.01) respectively. Moreover, patients with low miR-612 levels and high HADHA levels had a poor prognosis with shorter overall survival., Conclusion: miR-612 can suppress the formation of invadopodia, EMT, and HCC metastasis and by HADHA-mediated lipid programming, which may provide a new insight of miR-612 on tumor metastasis and progression.

Aim: The slow coronary flow (SCF) phenomenon was characterized by delayed perfusion of epicardial arteries, and no obvious coronary artery lesion in coronary angiography. The prognosis of patients with slow coronary flow was poor. However, there is lack of rapid, simple, and accurate method for SCF diagnosis. This study aimed to explore the utility of plasma choline as a diagnostic biomarker for SCF., Methods: Patients with coronary artery stenosis <40% evaluated by the coronary angiogram method were recruited in this study and were grouped into normal coronary flow (NCF) and SCF by thrombolysis in myocardial infarction frame count (TFC). Plasma choline concentrations of patients with NCF and SCF were quantified by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry. Correlation analysis was performed between plasma choline concentration and TFC. Receiver operating characteristic (ROC) curve analysis with or without confounding factor adjustment was applied to predict the diagnostic power of plasma choline in SCF., Results: Forty-four patients with SCF and 21 patients with NCF were included in this study. TFC in LAD, LCX, and RCA and mean TFC were significantly higher in patients with SCF in comparison with patients with NCF (32.67 ± 8.37 vs. 20.66 ± 3.41, P   <  0.01). Plasma choline level was obviously higher in patients with SCF when compared with patients with NCF (754.65 ± 238.18 vs. 635.79 ± 108.25, P =0.007). Plasma choline level had significantly positive correlation with Mean TFC ( r  = 0.364, P =0.002). Receiver operating characteristic (ROC) analysis showed that choline with or without confounding factor adjustment had an AUC score of 0.65 and 0.77, respectively., Conclusions: TFC were closely related with plasma choline level, and plasma choline can be a suitable and stable diagnostic biomarker for SCF., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Yuan-Ting Zhu et al.)

Objective: To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by Young 's modulus of ultrasonic wave, and seek an objective evaluating method., Methods: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone ( Young 's modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment., Results: Compared before treatment, the VAS scores, Young 's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all P <0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both P <0.05). In the observation group, the VAS scores, Young 's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all P <0.05)., Conclusion: The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.

Frailty syndrome, caused by degenerative changes in the body and the body vulnerability due to a variety of chronic diseases, is associated with adverse outcomes, such as fall, disability and mortality. With the development of antiretroviral therapy, the average life span of HIV/AIDS patients is extended, the number of elderly living with HIV/AIDS has increased, resulting the increase of the incidence of frailty syndrome in this population. The incidence of frailty syndrome in the elderly is associated with HIV infection and adverse reaction of antiretroviral therapy. Early assessment and intervention of frailty syndrome in elderly HIV/AIDS patients can reduce adverse clinical events and improve the quality of life.

Our previous study demonstrated that heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) is a key gene that facilitates metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms behind this relationship are not fully understood. In our study, we utilized long-noncoding RNA (lncRNA) microarrays to identify a HNRNPAB-regulated lncRNA named lnc-ELF209. Our findings from chromatin immunoprecipitation assays indicate that HNRNPAB represses lnc-ELF209 transcription by directly binding to its promoter region. We also analyzed clinical samples from HCC patients and cell lines with quantitative real-time polymerase chain reactions, RNA in situ hybridization and immunohistochemistry, and found that there is a negative relationship between HNRNPAB and lnc-ELF209 expression. Up/downregulation assays and rescue assays indicate that lnc-ELF209 inhibits cell migration, invasion and epithelial-mesenchymal transition regulated by HNRNPAB. This suggests a new regulatory mechanism for HNRNPAB-promoted HCC progression. RNA pull-down and LC-MS/MS were used to determine triosephosphate isomerase, heat shock protein 90-beta and vimentin may be involved in the tumor-suppressed function of lnc-ELF209. Furthermore, we found lnc-ELF209 could stabilize TPI protein expression. We also found that lnc-ELF209 overexpression in HCCLM3 cell resulted in a lower rate of lung metastatic, which suggested a less aggressive HCC phenotype. Collectively, these findings offer new insights into the regulatory mechanisms that underlie HNRNPAB cancer-promoting activities and demonstrate that lnc-ELF209 is a HNRNPAB-regulated lncRNA that may play an important role in the inhibition of HCC progression., (© 2019 UICC.)

In theory, quantum key distribution (QKD) can offer information-theoretic secure communication based on the laws of quantum mechanics. However, the vast majority of practical QKD implementations assume the perfect state preparation to ensure security, which is a demanding requirement with current technology. Here, by incorporating the mismatched-basis data, we report an experimental decoy-state QKD demonstration with uncharacterized encoding sources, which only requires that the encoding states are two-dimensional. Furthermore, the measurement operation of the receiver is loosened to be projective measurements. With a rigorous statistical fluctuation analysis, we can distribute secret keys when the transmission distances of the standard fiber link are 101 and 202 km. Our experimental demonstration represents a significant step toward realizing long-distance quantum communication, even with uncharacterized sources and projective measurements.

X-linked adrenoleukodystrophy (X-ALD) is the most frequent type of inherited demyelinating peroxisomal disease caused by mutations in the ATP binding cassette subfamily D member 1 (ABCD1) gene. The rate of early recognition and genetic diagnosis of X-ALD remains low due to its variable clinical manifestations. The present study summarized the clinical features Chinese X-ALD patients and performed a follow-up study to further precisely characterize this disease. A total of 10 patients diagnosed with X-ALD between 1994 and 2016 at Shandong Provincial Hospital Affiliated to Shandong University (Jinan, China) were included in the present study. Through reviewing their medical records and performing telephone follow-ups, the clinical features, biochemical laboratory data, brain images, treatments and long-term outcomes were retrospectively summarized. Mutation analysis of the ABCD1 gene was performed in certain patients. Most of the patients (8/10) had the childhood cerebral form of X-ALD. One patient presented with the olivo-ponto-cerebellar form, the rarest form of X-ALD. In all patients, brain magnetic resonance images revealed abnormalities with typical T2-weighted hyperintensity. Analysis of very long chain fatty acid revealed high plasma levels of hexacosanoic acid in all patients. Increased adrenocorticotropic hormone, decreased cortisol and neurophysiological manifestations were also observed. Three different mutations of the ABCD1 gene were identified in the 3 patients subjected to genotyping. During the follow-ups, most patients took neurotrophic drugs and received hydrocortisone replacement when required. One patient received a hematopoietic stem cell transplantation, but died 1 year following the transplantation. Chronic myelopathy and peripheral neuropathy progressed with time, gradually leading to a vegetative state or paralysis within several years of clinical symptom onset. In conclusion, male patients with adrenocortical insufficiency should be further investigated for X-ALD. Early detection is critical to prevent the progression of X-ALD with mutation analysis of ABCD1 the most accurate method to confirm diagnosis.

Background : Fucoidan is a fucose-enriched, sulfated polysaccharide found in brown algae; in recent years, this polysaccharide has been found to exert several biological effects, including antitumor effects, such as antiproliferation, activating apoptosis, and anti-angiogenesis of cancer cells. However, the antimetastatic effect of fucoidan and the related targeting receptors remain unknown. In the present study, we examined the inhibition of invadopodia formation and underlying mechanism of fucoidan on human liver cancer cells. Methods : We used 98% purified fucoidan from Sargassum species to treat the hepatocellular carcinoma (HCC) cells SMMC-7721, Huh7 and HCCLM3 in vitro and the HCCLM3 cell line in vivo . The HCC cells were cultured with various concentrations of Fucoidan-Sargassum (0-30 mg/mL). Migration, invasion and wound healing assays were performed to determine the antimetastatic effect of fucoidan on the HCC cells. Western blot analysis and immunofluorescence staining were conducted to determine the expression levels of invadopodia formation-regulating proteins and the targeting membrane receptor proteins. Results : Fucoidan-Sargassum inhibited the migration and invasion of HCC SMMC-7721, Huh7 and HCCLM3 cells in a dose-dependent manner. In the HCCLM3 cells, Fucoidan-Sargassum also decreased the expression levels of invadopodia-related proteins including Src, Cortactin, N-WASP, ARP3, CDC42, MMP2, MT1-MMP, and the targeting receptors integrin αV and β3 in a dose-dependent manner. Fucoidan-Sargassum also increased the levels of endoplasmic reticulum-related proteins, including GRP78, IRE1, SPARC, and the type IV collagen receptor proteins integrin α1 and β1. In vivo , Fucoidan-Sargassum reduced the size of liver tumors and decreased the number of lung metastatic foci in nude mice with hepatocellular carcinoma xenografts. Conclusion : These findings indicate that Fucoidan-Sargassum has an antimetastatic effect on SMMC-7721, Huh7 and HCCLM3 liver cancer cells, and the underlying mechanism involves targeting ITGαVβ3 and mediating the ITGαVβ3/SRC/E2F1 signaling pathway. These results suggest that Fucoidan-Sargassum may be a promising therapeutic antimetastatic compound in the development of a metastasis-preventive drug for treating liver cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Natural killer (NK) cell can inhibit tumor initiation and regulates metastatic dissemination, acting as key mediators of the innate immune response. Intrinsic factors modulating NK cells infiltration and its anticancer activity remain poorly characterized. We investigated the roles of dysregulation of micro(mi)RNAs and NK cells in progression of hepatocellular carcinoma (HCC). Methods : Small RNA sequencing were used to detect the miRNA profiles of tumor tissues from HCC patients with (n=14) or without (n=13) pulmonary metastasis and HCC cell lines with different pulmonary metastatic potentials. Chemokine expression profiling and bioinformatics were used to detect the downstream target of candidate target. In gain- and loss-of-function assays were used to investigate the role of miRNA in HCC progression. Different subsets of NK cells were isolated and used for chemotaxis and functional assays in vivo and in vitro . In situ hybridization and immunohistochemical analyses were performed to detect the expression of miRNA in tumor tissues from 242 HCC patients undergoing curative resection from 2010. Results : Three miRNAs (miR-137, miR-149-5p, and miR-561-5p) were identified to be associated with pulmonary metastasis in patients with HCC. miR-561-5p was most highly overexpressed in metastatic HCC tissues and high-metastatic-potential HCC cell lines. In gain- and loss-of-function assays in a murine model, miR-561-5p promoted tumor growth and spread to the lungs. Yet, miR-561-5p did not appear to affect cellular proliferation and migration in vitro . Bioinformatics and chemokine expression profiling identified chemokine (C-X 3 -C motif) ligand 1 (CX 3 CL1) as a potential target of miR-561-5p. Furthermore, miR-561-5p promoted tumorigenesis and metastasis via CX 3 CL1-dependent regulation of CX 3 CR1 + NK cell infiltration and function. CX 3 CR1 + NK cells demonstrated stronger in vivo anti-metastatic activity relative to CX 3 CR1 - NK cells. CX 3 CL1 stimulated chemotactic migration and cytotoxicity in CX 3 CR1 + NK cells via STAT3 signaling. Blockade of CX 3 CL1, CX 3 CR1, or of pSTAT3 signaling pathways attenuated the antitumor responses. Clinical samples exhibited a negative correlation between miR-561-5p expression and levels of CX 3 CL1 and CX 3 CR1 + NK cells. High miR-561-5p abundance, low CX 3 CL1 levels, and low numbers of CX 3 CR1 + NK cells were associated with adverse prognosis. Conclusion : We delineated a miR-561-5p/CX3CL1/NK cell axis that drives HCC metastasis and demonstrated that CX 3 CR1 + NK cells serve as potent antitumor therapeutic effectors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: We aimed to study the incidence rate of hypoparathyroidism, its risk factors, and identify its predictive factors among patients with papillary thyroid carcinoma (PTC) who had undergone total or near-total thyroidectomy and central neck dissection (CND)., Methods: Ninety-three PTC patients who had undergone total or near-total thyroidectomy and CND were analyzed for hypoparathyroidism. The association between clinicopathological factors and hypoparathyroidism was tested by χ 2 test and multivariate logistic regression. The ROC curve and a 2×2 contingency table were used to evaluate the performance of postoperative parathyroid hormone (PTH) and serum calcium concentration in prediction of hypothyroidism., Results: Hypothyroidism was observed in 46 patients (49.5%), among whom 2 had permanent hypothyroidism. Univariate analysis showed that tumor size (P=0.034), extraglandular invasion (P=0.028), bilateral tumors (P=0.045), and bilateral CND (P=0.028) were significant risk factors of hypothyroidism. Multivariate analysis showed that extraglandular invasion (P=0.003) and bilateral CND (P=0.044) were independent risk factors. The patients with hypothyroidism had an average PTH level of 8.51 ng/L on the first day after surgery, and those without, 21.39 ng/L (P<0.001). When the PTH level on the first day after surgery was used to predict postoperative hypothyroidism, the ROC curve analysis showed that the area under curve (AUC) was 0.875., Conclusions: Hypothyroidism is a common complication of total or near-total thyroidectomy and CND, for which extraglandular invasion and bilateral CND are independently significant risk factors and the level of PTH is a reliable and early predictor., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.02.02). The authors have no conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Vascular endothelial dysfunction is the major contributing factor to hypertension. Endothelial progenitor cells (EPCs) are essential for endogenous vascular endothelial renovation. The activity and number of circulating EPCs are preserved in prehypertensive premenopausal females according to our previous research. However, the changes of EPCs in prehypertensive postmenopausal females are poorly understood, and the mechanisms responsible for the loss of the gender protection advantage of cardiovascular disease remain unexplored. In order to determine the effects of EPCs in prehypertensive postmenopausal females, the number and activity of circulating EPCs were tested in the present study. Next, the function of EPCs secreting nitric oxide (NO), vascular endothelial growth factor (VEGF) and granulocyte‑macrophage colony‑stimulating factor (GM‑CSF), as well as their concentration in the plasma, were measured. The association between flow‑mediated dilation (FMD) and EPC secretion was also assessed. Attenuation of proliferation and migration of EPCs was observed in prehypertensive patients in comparison with normotensive subjects. In addition, a reduced NO production secreted by EPCs was detected in prehypertensive patients as compared with that in normotensive patients. There was no significant difference in EPC function between postmenopausal females and age‑matched males. Finally, the association between FMD and NO production was validated. Collectively, these data indicated that impaired EPCs mediated vasodilation dysfunction via decreasing NO production. Therefore, EPC function enhancement and NO level augmentation are emerging as novel therapeutic strategies for prehypertension therapy.

Objective: Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) is a safe and effective method of screening malignant thyroid nodules such as papillary thyroid carcinoma. However, not much data are available regarding the diagnostic efficacy of US-FNAB for papillary thyroid microcarcinoma (≤10 mm in diameter). We aim to compare the diagnostic efficacy of US-FNAB on thyroid nodules between two groups divided by a diameter of 10 mm by correlating the cytological results of US-FNAB with the histopathologic diagnoses in selected patients., Patients and Methods: Eight hundred twenty-two thyroid nodules (Group A: diameter ≤10 mm, n=620; Group B: diameter >10 mm, n=202) from 797 patients treated between March 2014 and June 2017 were retrospectively evaluated. Only nodules with Thyroid Imaging Reporting and Data System (TIRADS) categories 4-6 were enrolled and sampled by US-FNAB, followed by surgical resection., Results: According to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories, 94 thyroid nodules were classified as I, III and IV, and were excluded from the analysis. The resultant 728 thyroid nodules from 721 patients were analyzed. The malignant tendency (TBSRTC V and VI) rates on US-FNAB were 88.2% and 84.6% ( P= 0.202) in Group A and Group B, respectively, and the malignant rates were 89.5% and 86.9% ( P =0.330), respectively, on histopathology. There was a high concordance between cytology and histopathology diagnoses (kappa value =0.797), and no statistical difference in terms of US-FNAB accuracy was found between the two groups ( P =0.533)., Conclusion: For thyroid nodules of TIRADS category 4-6, the diagnostic efficacy of US-FNAB is similar for thyroid nodules either smaller or greater than 10 mm in their maximum diameter., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Angiogenesis is critical for re-establishing the blood supply to the surviving myocardium after myocardial infarction (MI) in patients with acute coronary syndrome (ACS). MicroRNAs are recognised as important epigenetic regulators of endothelial function. The aim of this study was to determine the roles of microRNAs in angiogenesis. Eighteen circulating microRNAs including miR-185-5p were differently expressed in plasma from patients with ACS by high-throughput RNA sequencing. The expressional levels of miR-185-5p were dramatically reduced in hearts isolated from mice following MI and cultured human umbilical vein endothelial cells (HUVECs) under hypoxia, as determined by fluorescence in situ hybridisation and quantitative RT-PCR. Evidence from computational prediction and luciferase reporter gene activity indicated that cathepsin K (CatK) mRNA is a target of miR-185-5p. In HUVECs, miR-185-5p mimics inhibited cell proliferations, migrations and tube formations under hypoxia, while miR-185-5p inhibitors performed the opposites. Further, the inhibitory effects of miR-185-5p up-regulation on cellular functions of HUVECs were abolished by CatK gene overexpression, and adenovirus-mediated CatK gene silencing ablated these enhancive effects in HUVECs under hypoxia. In vivo studies indicated that gain-function of miR-185-5p by agomir infusion down-regulated CatK gene expression, impaired angiogenesis and delayed the recovery of cardiac functions in mice following MI. These actions of miR-185-5p agonists were mirrored by in vivo knockdown of CatK in mice with MI. Endogenous reductions of miR-185-5p in endothelial cells induced by hypoxia increase CatK gene expression to promote angiogenesis and to accelerate the recovery of cardiac function in mice following MI., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Accumulation of evidence indicates that miRNAs have crucial roles in the regulation of EMT-associated properties, such as proliferation, migration and invasion. However, the underlying molecular mechanisms are not entirely illustrated. Here, we investigated the role of miR-296-5p in hepatocellular carcinoma (HCC) progression., Methods: In vitro cell morphology, proliferation, migration and invasion were compared between HCC cell lines with up- or down-regulation of miR-296-5p. Immunofluorescence and Western blot immunofluorescence assays were used to detect the expression of EMT markers. Bioinformatics programs, luciferase reporter assay and rescue experiments were used to validate the downstream targets of miR-296-5p. Xenograft nude mouse models were established to observe tumor growth and metastasis. Immunohistochemical assays were conducted to study the relationships between miR-296-5p expression and Neuregulin-1 (NRG1)/EMT markers in human HCC samples and mice., Results: miR-296-5p was prominently downregulated in HCC tissues relative to adjacent normal liver tissues and associated with favorable prognosis. Overexpression of miR-296-5p inhibited EMT along with migration and invasion of HCC cells via suppressing NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling in vitro. More importantly, miR-296-5p disrupted intrahepatic and pulmonary metastasis in vivo. NRG1, as a direct target of miR-296-5p, mediates downstream biological responses. In HCC tissues from patients and mice, the levels of miR-296-5p and NRG1 also showed an inverse relationship., Conclusions: miR-296-5p inhibited EMT-related metastasis of HCC through NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling.

To explore the influence of prostate size on the outcome of Plasmakinetic enucleation of the prostate (PkEP) for the treatment of benign prostate hyperplasia (BPH), The data of 892 patients with symptomatic BPH who underwent PkEP were retrospectively reviewed. Among them, 199 (22.31%) had the prostate size smaller than 40 g (Group 1), 409 (45.85%) between 40 and 79 g (Group 2), 197 (22.09%) between 80 and 120 g (Group 3), and 87 (9.75%) larger than 120 g (Group 4). Perioperative variables, perioperative and postoperative complications were recorded. Patients were followed up for 36 months postoperatively. The efficiency of the surgery increased as the prostate size increased. Greater decreases in hemoglobin were noted in groups with larger prostates, while the duration of catheterization after the operation was similar across all groups. During the 3-year follow-up, the postoperative improvement in International Prostate Symptom Score (IPSS), Quality of Life (QOL), maximal flow rate (Qmax) and post-void residual urine volume (PVR), as well as longterm complications including urethral stricture and bladder-neck contracture were comparable across the 4 groups. These findings revealed that PkEP is more efficient for large prostate and can treat all prostates regardless of the size with equivalent symptom relief and micturition improvement., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

BACKGROUND Colorectal cancer is one of the leading causes of death in China, and the development of effective drugs is urgently needed. Here, we report on Paeoniflorin (PF), a product isolated from the roots of the peony plant, as a possible candidate because of its anti-tumor effects on epithelial-to-mesenchymal transition (EMT) of PF in human colorectal cancer (CRC). MATERIAL AND METHODS Cell proliferation, wound healing, and Transwell assays were used to analyze the effects of PF on in vitro cell migration and invasion of HCT116 and SW480, 2 colorectal cancer cell lines. The tumor xenograft model was used to verify the anti-metastasis effects of PF in vivo. The RNA and protein levels of epithelia-cadherin (E-cadherin), Vimentin, and histone deacetylase2 (HDAC2) were measured by qPCR and Western blot analysis to explore the mechanism involved. RESULTS Our results showed that PF inhibited colorectal cancer cell migration and invasion and suppressed the metastatic potential of the cancer cells in vivo. Moreover, PF significantly decreased the expression of HDAC2 and Vimentin, while increasing the expression of E-cadherin. CONCLUSIONS These results suggest that PF inhibits colorectal cancer cell migration and invasion ability and reverses the EMT process, through inhibiting the expression of HDAC2, and then affects the expression level of E-cadherin and Vimentin at the cell level. Our results were also verified in the tumor xenograft model. This indicates that PF may be a candidate for colorectal cancer treatment.

Two kinds of hybrid two-step multi-soil-layering (MSL) systems loaded with different filter medias (zeolite-ceramsite MSL-1 and ceramsite-red clay MSL-2) were set-up for the low-(C/N)-ratio polluted river water treatment. A long-term pollutant removal performance of these two kinds of MSL systems was evaluated for 214 days. By-pass was employed in MSL systems to evaluate its effect on nitrogen removal enhancement. Zeolite-ceramsite single-pass MSL-1 system owns outstanding ammonia removal capability (24 g NH 4 + -Nm -2 d -1 ), 3 times higher than MSL-2 without zeolite under low aeration rate condition (0.8 × 10 4  L m -2 .h -1 ). Aeration rate up to 1.6 × 10 4  L m -2 .h -1 well satisfied the requirement of complete nitrification in first unit of both two MSLs. However, weak denitrification in second unit was commonly observed. By-pass of 50% influent into second unit can improve about 20% TN removal rate for both MSL-1 and MSL-2. Complete nitrification and denitrification was achieved in by-pass MSL systems after addition of carbon source with the resulting C/N ratio up to 2.5. The characters of biofilms distributed in different sections inside MSL-1 system well illustrated the nitrogen removal mechanism inside MSL systems. Two kinds of MSLs are both promising as an appealing nitrifying biofilm reactor. Recirculation can be considered further for by-pass MSL-2 system to ensure a complete ammonia removal., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: This research aimed to investigate whether metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) had both individual and synergistic effects on the prognosis for female colorectal carcinoma (CRC) patients., Methods: The relationship between CRC prognosis and NAFLD as well as MetS was evaluated in 764 female participants. Based on the NAFLD level, patients were divided into significant NAFLD (SNAFLD), "moderate" and "severe" level, and non-SNAFLD, "non" and "mild" level. All the patients were categorized into four subgroups according to the status of SNAFLD and MetS and then a comparison of CRC prognosis among those four groups was performed., Results: NAFLD, SNAFLD, and MetS were independent factors for CRC-specific mortality with the adjustment of age and other confounders. The hazard ratio (HR) of CRC-specific mortality in MetS (+) SNAFLD (+) group was significantly higher than that in other three groups. Relative excess risk of interaction (RERI) was 2.203 with 95% CI ranged from 0.197 to 4.210, attributable proportion (AP) was 0.444 with range from 0.222 to 0.667, and synergy index (SI) of 2.256 with 95% CI from 1.252 to 4.065, indicating SNAFLD and MetS had a significant synergic effect on CRC-specific mortality., Conclusions: SNAFLD and MetS are independent risk factors for CRC-specific mortality in females. Moreover, those two diseases have a synergistic effect on promoting CRC-specific mortality.

Background: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers., Methods: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model., Findings: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo., Interpretation: Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194)., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by nitrate tolerance, because of the dysfunction of prostaglandin I2 synthase (PTGIS). MicroRNAs repress target gene expression and are recognized as important epigenetic regulators of endothelial function. The aim of this study was to determine whether nitrates induce nitrovasodilator resistance via microRNA-dependent repression of PTGIS gene expression., Methods: Nitrovasodilator resistance was induced by nitroglycerin (100 mg·kg -1 ·d -1 , 3 days) infusion in Apoe -/- mice. The responses of aortic arteries to nitric oxide donors were assessed in an organ chamber. The expression levels of microRNA-199 (miR-199)a/b were assayed by quantitative reverse transcription polymerase chain reaction or fluorescent in situ hybridization., Results: In cultured human umbilical vein endothelial cells, nitric oxide donors induced miR-199a/b endogenous expression and downregulated PTGIS gene expression, both of which were reversed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt or silence of serum response factor. Evidence from computational and luciferase reporter gene analyses indicates that the seed sequence of 976 to 982 in the 3'-untranslated region of PTGIS mRNA is a target of miR-199a/b. Gain functions of miR-199a/b resulting from chemical mimics or adenovirus-mediated overexpression increased PTGIS mRNA degradation in HEK293 cells and human umbilical vein endothelial cells. Furthermore, nitroglycerin-decreased PTGIS gene expression was prevented by miR-199a/b antagomirs or was mirrored by the enforced expression of miR-199a/b in human umbilical vein endothelial cells. In Apoe -/- mice, nitroglycerin induced the ectopic expression of miR-199a/b in the carotid arterial endothelium, decreased PTGIS gene expression, and instigated nitrovasodilator resistance, all of which were abrogated by miR-199a/b antagomirs or LNA-anti-miR-199. It is important that the effects of miR-199a/b inhibitions were abolished by adenovirus-mediated PTGIS deficiency. Moreover, the enforced expression of miR-199a/b in vivo repressed PTGIS gene expression and impaired the responses of aortic arteries to nitroglycerin/sodium nitroprusside/acetylcholine/cinaciguat/riociguat, whereas the exogenous expression of the PTGIS gene prevented nitrovasodilator resistance in Apoe -/- mice subjected to nitroglycerin infusion or miR-199a/b overexpression. Finally, indomethacin, iloprost, and SQ29548 improved vasorelaxation in nitroglycerin-infused Apoe -/- mice, whereas U51605 induced nitrovasodilator resistance. In humans, the increased expressions of miR-199a/b were closely associated with nitrate tolerance., Conclusions: Nitric oxide-induced ectopic expression of miR-199a/b in endothelial cells is required for nitrovasodilator resistance via the repression of PTGIS gene expression. Clinically, miR-199a/b is a novel target for the treatment of nitrate tolerance.

Here, we aimed to investigate the carcinogenic effects of apolipoprotein C1 (APOC1) in prostate cancer (PCa). APOC1 expression was evaluated in PCa and normal prostate specimens, and lentivirus-mediated RNA interference was used to knockdown APOC1 in DU145 cells. The effects of APOC1 silencing on cell proliferation, cell cycle arrest, and apoptosis were assessed. APOC1 expression was much higher in PCa tissues than in normal tissues. Moreover, APOC1 silencing inhibited cell proliferation and colony formation, arrested cell cycle progression, and enhanced apoptosis in DU145 cells. Additionally, APOC1 silencing decreased survivin, phospho-Rb, and p21 levels and increased cleaved caspase-3 expression. These data supported the procarcinogenic effects of APOC1 in the pathogenesis of PCa and suggested that targeting APOC1 may have applications in the treatment of PCa., (© 2018 The Authors. Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals, Inc.)

Endothelial progenitor cells (EPCs) contribute to the endogenous endothelial repair program during hypercholesterolemia. EPC count and migratory and proliferative capacities remain unchanged in the premenopausal female with hypercholesterolemia. However, the changes of count and activity of circulating EPCs in the hypercholesterolemic postmenopausal females are unknown. Here, we find that the migratory and proliferative capacities of circulating EPCs were decreased in patients with hypercholesterolemia versus normocholesterolemia. No significant differences were found between postmenopausal females and age-matched males. NO production showed positive correlation with the activity and count of circulating EPCs in patients with hypercholesterolemia. Flow-mediated dilatation (FMD) is directly interrelated with EPC counts and function. Our findings reveal that decreased EPC count and endothelial dysfunction lead to less NO production in hypercholesterolemic postmenopausal females. Maintaining the EPC numbers and activity might be emerging as a potential therapeutic strategy to reduce the risk of cardiovascular injury in elder women.

Background: Drug resistance is one of the major concerns in the treatment of hepatocellular carcinoma (HCC). The aim of the present study was to determine whether aberrant high expression of the inhibitor of differentiation 1(ID1) confers oxaliplatin-resistance to HCC by activating the pentose phosphate pathway (PPP)., Methods: Aberrant high expression of ID1 was detected in two oxaliplatin-resistant cell lines MHCC97H-OXA(97H-OXA) and Hep3B-OXA(3B-OXA). The lentiviral shRNA or control shRNA was introduced into the two oxaliplatin-resistant cell lines. The effects of ID1 on cell proliferation, apoptosis and chemoresistance were evaluated in vitro and vivo. The molecular signaling mechanism underlying the induction of HCC proliferation and oxaliplatin resistance by ID1 was explored. The prognostic value of ID1/G6PD signaling in HCC patients was assessed using the Cancer Genome Atlas (TCGA) database., Results: ID1 was upregulated in oxaliplaitin-resistant HCC cells and promoted HCC cell proliferation and oxaliplatin resistance. Silencing ID1 expression in oxaliplaitin-resistant HCC cell lines inhibited cell proliferation and sensitized oxaliplaitin-resistant cells to death. ID1 knockdown significantly decreased the expression of glucose-6-phosphate dehydrogenase (G6PD), a key enzyme of the PPP. Silencing ID1 expression blocked the activation of G6PD, decreased the production of PPP NADPH, and augmented reactive oxygen and species (ROS), thus inducing cell apoptosis. Study of the molecular mechanism showed that ID1 induced G6PD promoter transcription and activated PPP through Wnt/β-catenin/c-MYC signaling. In addition, ID1/G6PD signaling predicted unfavorable prognosis of HCC patients on the basis of TCGA., Conclusions: Our study provided the first evidence that ID1 conferred oxaliplatin resistance in HCC by activating the PPP. This newly defined pathway may have important implications in the research and development of new more effective anti-cancer drugs.

The spinal origin of jaundice-induced altered peripheral nociceptive response poorly understood. In the current study, we aimed to first validate rats with bile duct ligation (BDL) as a jaundice model accompanied by altered peripheral nociceptive response, and then to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord on different time courses after BDL operation by using high-throughput RNA sequencing. The differentially expressed genes (DEGs) identified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, followed by clustering analysis, Gene Ontology analysis and pathway analysis. As a result, a total of 2033 lncRNAs were differentially expressed 28d after BDL, in which 1545 probe sets were up-regulated and 488 probe sets were down-regulated, whereas a total of 2800 mRNAs were differentially expressed, in which 1548 probe sets were up-regulated and 1252 probe sets were down-regulated. The RNAseq data of select mRNAs and lncRNAs was validated by RT-qPCR. 28d after BDL, the expressions of lncRNA NONRATT002335 and NONRATT018085 were significantly up-regulated whereas the expression of lncRNA NONRATT025415, NONRATT025388 and NONRATT025409 was significantly down-regulated. 14d after BDL, the expressions of lncRNA NONRATT002335 and NONRATT018085 were significantly up-regulated; the expression of lncRNA NONRATT025415, NONRATT025388 and NONRATT025409 was significantly down-regulated. In conclusion, the present study showed that jaundice accompanied with decreased peripheral nociception involved in the changes of gene and lncRNA expression profiles in spinal cord. These findings extend current understanding of spinal mechanism for obstructive jaundice accompanied by decreased peripheral nociception., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest related to this paper.

Isobavachalcone (2',4',4-trihydroxy-3'-[3'-methylbut-3'-ethyl] chalcone or IBC) exhibits anticancer activities in a number of types of cancer cell. However, its role in tongue squamous cell carcinoma (TSCC) cells remains unclear. The aim of the present study was to investigate the biological effect of IBC in TSCC Tca8113 cells. The function of IBC on Tca8113 cell apoptosis and apoptosis-associated signaling pathways was determined using an MTT assay, morphological staining, annexin V-propidium iodide (PI) staining and Western blot analysis. The effects of IBC on Tca8113 cell migration, invasion and relative protein expression were confirmed using wound healing analysis, Transwell invasion analysis and Western blot analysis, respectively. The results of the MTT assay and annexin V-PI staining indicated that IBC is able to significantly inhibit proliferation and induce apoptosis of Tca8113 cells in vitro . IBC treatment resulted in typical apoptotic morphology of nuclear fragmentation and apoptotic bodies in Tca8113 cells. Western blot analysis further demonstrated that IBC caused downregulation of the expression of B-cell lymphoma 2 (Bcl-2) protein, upregulation of the expression of Bcl-2-associated X protein (Bax), activation of caspases, and dephosphorylation of protein kinase B (Akt) and extracellular-signal-regulated kinase (ERK) proteins in a concentration- and time-dependent manner. The results of the present study suggest that IBC induces apoptosis in Tca8113 cells and that the induction may be associated with the activation of Bcl-2, Bax and caspase-3, and the inactivation of Akt and ERK. Furthermore, IBC inhibited migration and invasion of Tca8113 cells in vitro by downregulating matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. The results of the present study indicate that IBC may be a potential anticancer drug for the treatment of TSCC.

Objective: To analyze the concentrations of nesfatin-1 in maternal and cord serum, to evaluate the expression of nesfatin-1 in subcutaneous adipose tissue (SAT) from pregnant women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT)., Methods: We studied a total of 50 GDM and 50 NGT subjects. The clinical features, serum nesfatin-1, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles were measured at the third trimester of pregnancy. The expression of nesfatin-1 in the SAT was determined by western blot., Results: Compared with the NGT group, the GDM group showed greater levels of serum nesfatin-1, adipocyte fatty acid binding protein (AFABP), and leptin; a greater level of cord blood nesfatin-1; and a higher level of expression in SAT (p < 0.05 or p < 0.01). Fasting insulin (FI) (b = 0.317, p= 0.022) and body mass index (BMI) before delivery (b = 0.367, p=0.008) were independently associated with serum nesfatin-1. Nesfatin-1 was the independent risk factor for GDM., Conclusions: The GDM group had higher levels of maternal serum and cord blood nesfatin-1, and greater nesfatin-1 expression in SAT. Nesfatin-1 is closely related to obesity and IR in pregnancy.

A highly selective para C-H amination of unprotected phenols with iminoquinone acetals was realized, giving the functional phenols in good to excellent yields. Overall, this transformation is operationally simple, proceeds with readily available phenols, and has wide substrate scope and low catalyst loading. The biarylamine product is stochastically formed via [5,5]-sigmatropic rearrangement of a mixed acetal species which is generated in situ under the reaction conditions.

Objective: To further understand the interaction protein spectrum of heterogeneous ribonucleoprotein AB (hnRNP AB), and to investigate their clinical significance in hepatocellular carcinoma (HCC). Methods: We carried out mass spectrometry to reveal the specific peptides of KRAB-associated protein 1 (Kap1) and hnRNPAB, and verified their interaction by immunocoprecipitation and western blotting. Expression of hnRNPAB/Kap1 proteins were detected by immunohistochemical staining in the tissue microarrays. Categorical data were analyzed by the chi square test or Fisher exact test; enumeration data between groups were compared using Student t -test or Wilcocon signed rank test; the cumulative recurrence and survival rates were evaluated using the Kaplan-Meier method and the differences were assessed using the log-rank test. Results: We identified Kap1 as a molecular partner for hnRNPAB in HCCLM3 cells and HepG2 cells as well. We found that the 5-year survival rate of the Kap1high patients was significantly lower than the survival rate of those of the Kap1low group (36% vs 59% , HR = 1.67, P < 0.001). Similarly, Kap1high HCC patients had the poorest prognosis at 5-years, with higher cumulative recurrence rate than Kap1low patients (72% vs 54%, HR = 1.66, P = 0.001). Univariate and Multivariate analyses revealed that hnRNPAB /Kap1 alone ( HR = 1.35 /1.28, P = 0.001) or in combination with Kap1 ( HR =1.24 /1.27, P < 0.05) were independent prognostic indicators for overall survival and time to recurrence. Conclusion: In HCC cells, hnRNPAB and Kap1 form protein complexes. The expression levels of hnRNPAB alone or in combination with Kap1 in HCC patients are important because they provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.

Tralkoxydim is a cyclohexanedione herbicide primarily used for gramineous weed control in China. In this paper, we present results of a tralkoxydim laboratory environmental fate study characterizing its degradation, adsorption, and mobility behavior in three different soils and two water-sediment systems (river and lake) in China. Degradation half-life of tralkoxydim in soil under aerobic conditions was 5.1, 7.7, and 7.9 days in Jiangxi red soil, Taihu paddy soil, and Northeast China black soil, respectively. Under anaerobic and flooding conditions, half-life values were 6.2, 15.1, and 19.8 days for the same three soils, respectively. Soil pH was the major factor effecting tralkoxydim degradation. In the aerobic water-sediment experiments, tralkoxydim degraded faster in the river system (total system half-life 43.3 days) than the lake system (total system half-life 99.0 days). Correspondingly, its anaerobic degradation half-life values were 46.2 and 53.3 days for the river and lake systems, respectively. Tralkoxydim adsorption in the three soils was found to follow the empirical Freundlich isotherm. The adsorption coefficient (K d ) was 8.60, 1.00, and 1.57 for Jiangxi red soil, Taihu paddy soil, and Northeast China black soil, respectively. Soil pH was the major factor effecting tralkoxydim adsorption. Adsorption free energy change was less than 40 kJ mol -1 in all three soils, indicating a physical mechanism in the process. Thin-layer chromatography (TLC) tests showed that relative to the solvent transport to 11.5 cm, the travel distance of tralkoxydim was 8-10 cm in the three soils, corresponding Rf values at 0.05, 0.35, and 0.75 for Jiangxi red soil, Taihu paddy soil, and Northeast China black soil, respectively. Results of this work suggest that under alkaline conditions, tralkoxydim adsorption becomes smaller; thus, assessments on its mobility and potential groundwater impact should focus on these soil types.

Objective: To observe the effect of acupoint application on transforming growth factor (TGF)-β 1/Smad 3 signaling pathway, so as to reveal its mechanism underlying improvement of airway remodeling in chronic asthma mice., Methods: BALB/c mice were randomly divided into normal group,model group,sham acupoint application group (sham group),acupoint application group, and dexamethasone group ( n =8 in each group). The chronic asthma model was established by intraperitoneal injection of ovalbumin sensitization. The acupoint application group was treated with plaster composed with White Mustard Seed, Rhizoma Corydalis, Unprocessed Radix Kansui, and Herba Asari, on bilateral "Feishu" (BL 13), "Xinshu" (BL 15) and "Geshu" (BL 17) points, 6 hours a day for 14 days. The sham group was treated with plaster containing vaseline on bilateral BL 13, BL 15 and BL 17, 6 hours a day for 14 days. The dexamethasone group was treated with dexamethasone 1 mg·kg -1 ·day -1 intraperi-toneally, once daily for 14 days. At the end of treatment, airway resistance was detected by mouse lung function instrument. Patho-logical changes of airway were observed under light microscope after hematoxylin-eosin staining, and the morphological parameters were measured by image analysis software. Immunohistochemistry method was used to detect the expression of TGF-β 1 and Smad 3 in the lung tissue of mice., Results: Compared with the normal group, the airway resistance, the total bronchial wall area (WAt)/lumen perimeter (Pi), the smooth muscle wall area (WAm)/Pi, and the expression of TGF-β 1 and Smad 3 in the lung tissues were significantly higher in the model and sham groups ( P <0.01). Compared with the model group and the sham group, the airway resistance, WAt/Pi, WAm/Pi, the expression of TGF-β 1 and Smad 3 in the lung tissues were decreased in the acupoint application group and the dexamethasone group ( P <0.05). There were no significant differences between the acupoint application group and the dexamethasone group in the above mentioned indexes ( P >0.05)., Conclusions: Acupoint application can improve airway remodeling by down-regulating the expression of TGF-β 1/Smad 3 in the airway of chronic asthmatic mice.

Aim: To determine the role of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance imaging (MRI) using a bi-exponential model in chemotherapy response evaluation in a gastric cancer mouse model., Methods: Mice bearing MKN-45 human gastric adenocarcinoma xenografts were divided into four treated groups (TG1, 2, 3 and 4, n = 5 in each group) which received Fluorouracil and Calcium Folinate and a control group (CG, n = 7). DW-MRI scans with 14 b-values (0-1500 s/mm 2 ) were performed before and after treatment on days 3, 7, 14 and 21. Fast diffusion component (presumably pseudo-perfusion) parameters including the fast diffusion coefficient (D*) and fraction volume ( f p ), slow diffusion coefficient (D) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the IVIM model to the measured DW signals. The median changes from the baseline to each post-treatment time point for each measurement (ΔADC, ΔD* and Δ f p ) were calculated. The differences in the median changes between the two groups were compared using the mixed linear regression model by the restricted maximum likelihood method shown as z values. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. The median percentage changes were compared with the histopathological analyses between the pre- and post-treatment for each measurement., Results: Compared with the control group, D* in the treated group decreased significantly (ΔD* treated % = -30%, -34% and -20%, with z = -5.40, -4.18 and -1.95. P = 0.0001, 0.0001 and 0.0244) and f p increased significantly (Δ f ptreated % = 93%, 113% and 181%, with z = 4.63, 5.52, and 2.12, P = 0.001, 0.0001 and 0.0336) on day 3, 7 and 14, respectively. Increases in ADC in the treated group were higher than those in the control group on days 3 and 14 (z = 2.44 and 2.40, P = 0.0147 and P = 0.0164)., Conclusion: Fast diffusion measurements derived from the bi-exponential IVIM model may be more sensitive imaging biomarkers than ADC to assess chemotherapy response in gastric adenocarcinoma., Competing Interests: Conflict-of-interest statement: All authors declared that there was no conflict of interest related to this study.

Prostate-derived E-twenty-six (ETS) factor (PDEF), an epithelium-specific ETS transcription factor, regulates carcinogenesis and tumor progression. The prognostic importance and biologic functions in hepatocellular carcinoma (HCC) have not been established. We investigated PDEF expression in 400 HCC patients using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analysis. PDEF expression was significantly lower in tumors than in peritumoral tissues. Lower PDEF levels were associated with poorer prognosis in patients. PDEF was an independent predictor of overall survival in multivariate analysis. PDEF expression was suppressed in highly metastatic HCC cell lines, and shRNA-mediated down-regulation of PDEF in low-metastatic HCC cell lines (with high PDEF) significantly increased cellular proliferative and invasive capacity in vitro and in vivo . RNA sequencing analysis indicated that PDEF may mediate transcription of several genes involved in apoptosis and the cell cycle. PDEF modulated epithelial-mesenchymal transition by up-regulating E-cadherin expression and down-regulating Slug and Vimentin expression, thereby lowering migration and invasion abilities of HCC cells. In conclusion, PDEF is associated with proliferation and invasiveness of HCC cells. It may serve as an independent predictor of prognosis in patients with HCC., Competing Interests: CONFLICTS OF INTEREST The authors declared that they have no competing interest.