Skin marker combined with surface-guided auto-positioning for breast DIBH radiotherapy daily initial patient setup: An optimal schedule for both accuracy and efficiency.

BACKGROUND AND PURPOSE: By employing three surface-guided radiotherapy (SGRT)-assisted positioning methods, we conducted a prospective study of patients undergoing SGRT-based deep inspiration breath-hold (DIBH) radiotherapy using a Sentine/Catalys system. The aim of this study was to optimize the initial positioning workflow of SGRT-DIBH radiotherapy for breast cancer. MATERIALS AND METHODS: A total of 124 patients were divided into three groups to conduct a prospective comparative study of the setup accuracy and efficiency for the daily initial setup of SGRT-DIBH breast radiotherapy. Group A was subjected to skin marker plus SGRT verification, Group B underwent SGRT optical feedback plus auto-positioning, and Group C was subjected to skin marker plus SGRT auto-positioning. We evaluated setup accuracy and efficiency using cone-beam computed tomography (CBCT) verification data and the total setup time. RESULTS: In groups A, B, and C, the mean and standard deviation of the translational setup-error vectors were small, with the highest values of the three directions observed in group A (2.4 ± 1.6, 2.9 ± 1.8, and 2.8 ± 2.1 mm). The rotational vectors in group B (1.8 ± 0.7°, 2.1 ± 0.8°, and 1.8 ± 0.7°) were significantly larger than those in groups A and C, and the Group C setup required the shortest amount of time, at 1.5 ± 0.3 min, while that of Group B took the longest time, at 2.6 ± 0.9 min. CONCLUSION: SGRT one-key calibration was found to be more suitable when followed by skin marker/tattoo and in-room laser positioning, establishing it as an optimal daily initial set-up protocol for breast DIBH radiotherapy. This modality also proved to be suitable for free-breathing breast cancer radiotherapy, and its widespread clinical use is recommended.

Lesions in White Matter in Wilson's Disease and Correlation with Clinical Characteristics.

BACKGROUND: Neuroimaging studies in Wilson's disease (WD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these alterations are localized to specific regions of fiber tracts, and what diagnostic value they might have. The purpose of this study is to explore the spatial profile of WM abnormalities along defined fiber tracts in WD and its clinical relevance. METHODS: Ninety-nine patients with WD (62 men and 37 women) and 91 age- and sex-matched controls (59 men and 32 women) were recruited to take part in experiments of diffusion-weighted imaging with 64 gradient vectors. The data were calculated by FMRIB Software Library (FSL) software and Automated Fiber Quantification (AFQ) software. After registration, patient groups and normal groups were compared by Mann-Whitney U test analysis. RESULTS: Compared with the controls, the patients with WD showed widespread fractional anisotropy reduction and mean diffusivity, radial diffusivity elevation of identified fiber tracts. Significant correlations between diffusion tensor imaging (DTI) parameters and the neurological Unified Wilson's Disease Rating Scale (UWDRS-N), serum ceruloplasmin, and 24-h urinary copper excretion were found. CONCLUSIONS: The present study has provided evidence that the metrics of DTI could be utilized as a potential biomarker of neuropathological symptoms in WD. Damage to the microstructure of callosum forceps and corticospinal tract may be involved in the pathophysiological process of neurological symptoms in WD patients, such as gait and balance disturbances, involuntary movements, dysphagia, and autonomic dysfunction.

Molecular testing for H. pylori clarithromycin and quinolone resistance: a prospective Chinese study.

In China, there is a high prevalence of antibiotic-resistant Helicobacter pylori infections in the population. The aim of the study was to assess a new ARMS-PCR test for detection of H. pylori clarithromycin resistance (CR) and quinolone resistance (QR) mutations and evaluate the spectrum of antibiotic resistance in patients from three Chinese provinces. Sanger sequencing and multiplex ARMS-PCR were used to detect H. pylori CR and QR bacteria in gastric biopsy samples. Among the 1,182 patients enrolled with gastritis, 643 (54.4%) were positive for H. pylori. Of these, 371 (57.7%) had antibiotic-resistant strains, comprising 236 (63.6%) with a single drug antibiotic-resistant strain and 135 (36.4%) with multiple drug-resistant strains. Following Sanger sequencing analysis of 23S rRNA and gyrA gene for mutations (antibiotic resistance markers), rates of CR, QR, and multidrug resistance (CR and QR) were 19.9, 12.0, and 25.8%, respectively. The 23S rRNA CR mutation A2143G (286, 96.9%) and the gyrA QR mutations C261A (85, 31.5%) and G271A (71, 26.3%) were common. Benchmarking against Sanger sequencing results, multiplex ARMS-PCR test had a high diagnostic sensitivity and specificity for detection of CR (96 and 93%), QR (95 and 92%) and multidrug resistance (95 and 95%). Based on our findings, the high incidence of single and multiple antibiotic resistance requires the routine checking of antibiotic resistance in all patients with suspected H. pylori infections. Multiplex ARMS-PCR is a simple and rapid test that can be now used for more efficient treatment of H. pylori infections and reduces the misuse of antibiotics.

Paeonol alleviates dextran sodium sulfate induced colitis involving Candida albicans-associated dysbiosis.

Inflammatory bowel disease (IBD), which consists of ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disorder of the gastrointestinal tract. Occurrence and development of UC have been associated with multiple potential causative factors, which include fungal dysbiosis. Growing evidence reveals that Candida albicans-associated dysbiosis is correlated with clinical deterioration in UC. Paeonol (PAE) is a commonly used traditional medicine with multiple reported properties including effective alleviation of UC. In this study, a murine UC model was established by colonizing mice with additional C. albicans via gavage prior to dextran sodium sulfate (DSS) administration. Effects of PAE treatment were also assessed at initiation and in preestablished C. albicans-associated colitis. The results showed that C. albicans supplementation could aggravate disease activity index (DAI), compromise mucosal integrity, exacerbate fecal and tissue fungal burdens, increase serum ß-glucan and anti-Saccharomyces cerevisiae antibody (ASCA) levels, promote serum and colonic tissue pro-inflammatory cytokine secretion (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8) and decrease the anti-inflammatory cytokine IL-10 level. It also stimulated Dectin-1, TLR2 and TLR4 as well as expression of their downstream effector NF-κB in colonic tissue. After PAE treatment, the adverse impacts of C. albicans on colitis were relieved, via decreased receptor-associated local and systemic inflammation. Our study suggests that PAE should be a candidate for treatment of fungal dysbiosis-associated UC and may act through the Dectin-1/NF-κB pathway in collaboration with TLR2 and TLR4. LAY SUMMARY: Candida albicans is believed to be an important stimulator in ulcerative colitice (UC) development. Suppressing the growth of intestinal C. albicans can be contributory to the amelioration of UC. Paeonol (PAE) is a commonly used traditional medicine with multiple biological functions. In this study, we observed that PAE could alleviate symptoms in mice UC model accompanying with burden reduction of C. albicans. Therefore, we suppose that PAE can be a candidate in the treatment of C. albicans-associated UC.

Doctors' smoking control knowledge, attitudes and practices: a cross-sectional study conducted in Shandong Province, China.

BACKGROUND: Doctors play an important role in smoking control. This study aimed to assess doctors' smoking control knowledge, attitudes and practices to help doctors raise awareness of smoking control assistance. METHODS: This cross-sectional study recruited 1046 doctors from Shandong Province, China, by using multistage sampling. Participants' information was collected by questionnaire. Pearson's χ2 test and Fisher's exact probability method were used to compare the distributions of categorical variables between/among groups. RESULTS: Among the participants, 14.7% were current smokers. Approximately 50.3% of participants had heard of smoking cessation drugs and 59.2% of participants thought that low-tar and low-nicotine cigarettes were as harmful to health as common cigarettes. Approximately 98.2 and 60.9% of participants agreed that smoking was related to lung cancer and male sexual dysfunction, respectively. Although 72.0% of participants believed that doctors should actively provide smoking cessation assistance, only 58.1% of participants considered that doctors should be responsible for providing smoking cessation assistance. Similarly, 85.2% of participants often asked about the smoking history of patients or their family members, while only 4.9% of participants had prescribed smoking cessation drugs for patients. Pediatricians had a higher proportion of "Agree" responses to the assessment items than doctors in other departments. CONCLUSIONS: The results showed that doctors in Shandong Province did not have sufficient knowledge of smoking control. Slightly more than half of doctors thought that providing smoking cessation assistance was their responsibility. Only a few participants had prescribed smoking cessation drugs.

Sevoflurane inhibits the progression of ovarian cancer through down-regulating stanniocalcin 1 (STC1).

BACKGROUND: Ovarian cancer is one of the leading causes of female death worldwide, with a poor prognosis of advanced patients. Sevoflurane, a volatile anesthetic commonly used in clinical operations, has been reported to have anti-cancer activity against some tumors. In the present study, we aimed to investigate the effects of sevoflurane on the progression of ovarian cancer and its potential mechanism. METHODS: The effects of sevoflurane on ovarian cancer cell viability, proliferation, migration, invasion, cell cycle, and apoptosis were determined by functional experiments in vitro. Gelatin zymography assay was performed to examine MMP9 activity. In vivo, sevoflurane was injected into mice of transplantation tumor with SKOV3 cells or with pcDNA-STC1 treated SKOV3 cells. RESULTS: We found that sevoflurane inhibited the viability of SKOV3 and OVCAR3 cells in a dose-dependent manner, and colony formation assay revealed that sevoflurane inhibited ovarian cancer cell colony-formation abilities. Additionally, sevoflurane could induce cell cycle arrest and promote cell apoptosis in SKOV3 and OVCAR3 cells. Moreover, sevoflurane reduced the migration and invasion abilities of SKOV3 and OVCAR3 cells, as well as the MMP-9 activity. Furthermore, sevoflurane down-regulated the expression of stanniocalcin 1 (STC1), and up-regulation of STC1 could reverse the inhibitory effects of sevoflurane on cell proliferation and invasion. In vivo, sevoflurane significantly inhibited the tumor growth, which was be reversed by STC1 overexpression. CONCLUSION: These data reveal an anti-cancer activity of sevoflurane on the growth and invasion of ovarian cancer, which may be through down-regulating STC1. Sevoflurane may serve as a potential anti-cancer agent in ovarian cancer therapy.

Prediction of Response to Chemoradiotherapy by Dynamic Changes of Circulating Exosome Levels in Patients with Esophageal Squamous Cell Carcinoma.

Background: The exosomes-based liquid biopsy represents a prospective biomarker for tumor screening, prognosis prediction, and tumor regression. This study aimed to isolate circulating exosomes (CEs) from plasma of the esophageal squamous cell carcinoma (ESCC) patients who received chemoradiotherapy through exosome detection method via the ultrafast-isolation system (EXODUS) and investigated the association between the dynamic changes of CE levels and therapeutic effect. Methods: We isolated and quantitatively analyzed CEs from plasma of locally advanced ESCC patients received chemoradiotherapy at 2 time points: baseline (pre-chemoradiotherapy) and 2 months after the chemoradiotherapy (post-chemoradiotherapy). We isolated exosomes from plasma by EXODUS platform and confirmed them through nanoparticle tracking analysis (NTA), transmission electron microscope (TEM), and Western blot. The associations of CE level with clinicopathological characteristics, tumor regression, and progression-free survival (PFS) were analyzed. Results: The average diameter of CEs was 107.4±14.3 nm at baseline and 101.7±17.1 nm at post-chemoradiotherapy. The mean exosome concentration significantly decreased after chemoradiotherapy (7.3×1011 particles/mL vs 5.4×1011 particles/mL, P < 0.001). The patients with stage III-IVA and tumor length ≥5cm had obviously higher baseline CE levels. Dynamic changes in CE levels were successfully applied for evaluation of chemoradiotherapy response and PFS. Furthermore, through multivariate Cox regression analysis, it was revealed that dynamic changes of CE levels were an independent predictor of PFS in locally advanced ESCC patients who received chemoradiotherapy. Conclusion: Here, we demonstrated EXODUS platform isolated and enriched CEs from plasma of ESCC patients with high-purity and high-yield. The EXODUS platform can facilitate liquid biopsy based on exosomes translation to the clinic. Baseline CE levels can reflect ESCC tumor burden. The dynamic changes of CE levels during chemoradiotherapy allow the prediction of treatment effect and PFS of ESCC patients, requiring further investigations in larger patient cohorts.

Achieving ultra-high nitrogen and phosphorus removal from real municipal wastewater in a novel continuous-flow anaerobic/aerobic/anoxic process via partial nitrification, endogenous denitrification and nitrite-type denitrifying phosphorus removal.

Achieving economic and efficient removal of nutrients in mainstream wastewater treatment plants (WWTPs) continues to be a challenging research topic. In this study, a continuous-flow anaerobic/aerobic/anoxic system with sludge double recirculation (AOA-SDR), which integrated partial nitrification (PN), endogenous denitrification (ED) and nitrite-type denitrifying phosphorus removal (nDNPR), was constructed to treat real carbon-limited municipal wastewater. The average effluent concentrations of total inorganic nitrogen (TIN) and PO43--P during the stable operation period were 1.8 and 0.3 mg/L, respectively. PN was achieved with an average nitrite accumulation ratio of 90.4 % by combined strategies. Adequate storage of polyhydroxyalkanoates and glycogen in the anaerobic zone promoted the subsequent nitrogen removal capacity. In the anoxic zone, nitrite served as the main electron acceptor for the denitrifying phosphorus removal process. Mass balance analysis revealed that nDNPR contributed to 23.6 % of TIN removal and 44.7 % of PO43--P removal. The enrichment of Nitrosomonas (0.45 %) and Ellin 6067 (1.31 %), along with the washout of Nitrospira (0.15 %) provided the bacterial basis for the successful implementation of PN. Other dominant endogenous heterotrophic bacteria, such as Dechlormonas (10.81 %) and Candidatus Accumulibacter (2.96 %), ensured simultaneous nitrogen and phosphorus removal performance. The successful validation of integrating PN, ED and nDNPR for advanced nutrient removal in the AOA-SDR process provides a transformative technology for WWTPs.

Distribution of hepatitis C virus in eastern China from 2011 to 2020: a Bayesian spatiotemporal analysis.

Objective: This study aimed to evaluate the spatiotemporal distribution of patients with hepatitis C virus (HCV) and the factors influencing this distribution in Jiangsu Province, China, from 2011 to 2020. Methods: The incidence of reported HCV in Jiangsu Province from 2011 to 2020 was obtained from the Chinese Information System for Disease Control and Prevention (CISDCP). R and GeoDa software were used to visualize the spatiotemporal distribution and the spatial autocorrelation of HCV. A Bayesian spatiotemporal model was constructed to explore the spatiotemporal distribution of HCV in Jiangsu Province and to further analyze the factors related to HCV. Results: A total of 31,778 HCV patients were registered in Jiangsu Province. The registered incidence rate of HCV increased from 2.60/100,000 people in 2011 to 4.96/100,000 people in 2020, an increase of 190.77%. Moran's I ranged from 0.099 to 0.354 (P < 0.05) from 2011 to 2019, indicating a positive spatial correlation overall. The relative risk (RR) of the urbanization rate, the most important factor affecting the spread of HCV in Jiangsu Province, was 1.254 (95% confidence interval: 1.141-1.376), while other factors had no significance. Conclusion: The reported HCV incidence rate integrally increased in the whole Jiangsu Province, whereas the spatial aggregation of HCV incidence was gradually weakening. Our study highlighted the importance of health education for the floating population and reasonable allocation of medical resources in the future health work.

Water-filtered infrared A radiation hyperthermia combined with immunotherapy for advanced gastrointestinal tumours.

This study pioneered the use of WIRA whole-body infrared hyperthermia combined with ICI therapy to treat GIT and verified the feasibility and safety of HIT. The final results showed a DCR of 55.6%, with a median PFS of 53.5 days, median OS of 134 days, and an irAE incidence of 22.2%. Therefore, we believe that HIT can exert multiple synergistic sensitisation effects, thereby providing clinical benefits to patients with advanced GITs, increasing overall safety, and improving patients' QOL.

INTRODUCTION: This study aimed to validate the effectiveness, safety and feasibility of water­filtered infrared A radiation (WIRA) whole­body hyperthermia combined with immune checkpoint inhibitor (ICI) therapy (HIT) and evaluate the real­world clinical application prospects. METHODS: This open­label single­arm phase 2 clinical trial (NCT06022692) aimed to enrol advanced gastrointestinal tumour (GIT) patients with the MSS/pMMR phenotype. The patients were treated with whole­body hyperthermia on Days 1 and 8 of each HIT cycle along with administration of tislelizumab on Day 2. RESULTS: Between 1 June 2020 and 31 May 2022, 18 patients were enrolled in the study, including those with gastric cancer (n = 6), colon cancer (n = 7), rectal cancer (n = 3) and appendiceal cancer (n = 2). As of 19 May 2023, 17 of the 18 patients had died, including 14 deaths caused by tumour progression and three deaths caused by diseases other than cancer, while one patient was still undergoing follow­up. In terms of efficacy, the median DCR was 55.6%, while the median PFS and OS were 53.5 days and 134 days, respectively. Four patients (22.2%) experienced immune­related adverse events, and none of the patients reported grade 3 or higher irAEs. Hyperthermia was followed by an increase in the number of tumour immune­activated cells. CONCLUSIONS: HIT can provide survival benefits in patients with GITs by activating antitumour immune function and shows good safety and feasibility.

Improving the removal efficiency of nitrogen and organics in vertical-flow constructed wetlands: the correlation of substrate, aeration and microbial activity.

Four vertical-flow CWs (VFCWs) with different substrates and aeration conditions were studied on nutrient-removal capacity from synthetic wastewater. Zeolite substrate VFCWs (none-aerated: VFCW-1, aerated: VFCW-3) paralleled with ceramsite (none-aerated:VFCW-2, aerated: VFCW-4) were used to study the removal efficiencies of N and organics, the bacterial community, and the related functional genes. The results indicated that the pollutant removal efficiency was significantly enhanced by intermittent aeration. VFCW-4 (ceramsite with aeration) demonstrated a significant potential to remove NH4+-N (89%), NO3--N (78%), TN (71%), and COD (65%). VFCW-3 and VFCW-4 had high abundances of Amx, amoA, and nirK genes, which was related to NH4+-N and NO2--N removal. The microbial diversity and structure varied with aeration and substrate conditions. Proteobacteria, Actinobacteria, Candidatus, and Acidobacteria were the main bacteria phyla, with the average proportion of 38%, 21%, 19%, and 7% in the VFCWs. Intermittent aeration increased the abundance of Acidobacteria, which was conducive to the removal of organic matters. Overall, ceramsite substrate combined with intermittent aeration has a great potential in removing pollutants in VFCWs.

Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer.

Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibit the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

Metal tolerance capacity and antioxidant responses of new Salix spp. clones in a combined Cd-Pb polluted system.

To investigate the physiochemical characteristics of two new clones, Salix matsudana 'J172' (A7) and Salix matsudana 'Yankang1' (A64) in combined Cd-Pb contaminated systems, a hydroponic experiment was designed. The plant biomass, photosynthesis, antioxidant responses and the accumulation of metals in different plant parts (leaf, stem, and root) were measured after 35-day treatments with Cd (15, 30 µM) and Pb (250, 500 µM). The results showed that exposure to Cd-Pb decreased the biomass but increased the net photosynthetic rate for both A7 and A64, demonstrating that photosynthesis may be one of the metabolic processes used to resist Cd-Pb stress. Compared with control, roots exposed to Cd-Pb had higher activity of superoxide dismutase and more malondialdehyde concentrations, which indicated the roots of both clones were apt to be damaged. The concentrations of soluble protein were obviously higher in the roots of A64 than A7, indicating the roles of the antioxidative substance were different between two willow clones. Soluble protein also had significant relationship with translocation factors from accumulation in roots of A64, which illustrated it played important roles in the tolerance of A64 roots to heavy metals. The roots could accumulate more Pb rather than transport to the shoots compared with Cd. The tolerance index was more than 85% on average for both clones under all the treatments, indicating their tolerance capacities to the combined stress of Cd and Pb are strong under the tested metal levels. Both clones are the good candidates for phytoremediation of Cd and Pb by the root filtration in the combined contamination environment.

Enhanced ammonia synthesis activity of carbon-supported Mo catalyst by Mo carburization.

It is urgent to develop new efficient ammonia synthesis catalysts using non-precious metals. Herein, the Mo2C species is introduced into a carbon-supported Mo catalyst by in situ carburization of a carbon-supported Mo catalyst in H2. In combination with the presence of the Mo2C phase as well as the enhancement of the graphitization degree of carbon and the amount of the low-valent Mo species, the migration and the exchange of the adsorbed species with the gaseous species are accelerated. As a result, the catalyst with carbonization treatment shows higher ammonia synthesis activity than the sample without carbonization, and the ill effect of the poisoning of reagent gases also is alleviated.

The individual and combined effects of polystyrene and silver nanoparticles on nitrogen transformation and bacterial communities in an agricultural soil.

The effects of emerging contaminants micro/nanoplastics (MPs/NPs) and silver nanoparticles (Ag NPs) on health have attracted universal concern throughout the world. However, it is unclear on the combined effects of MPs/NPs and Ag NPs on the biogeochemistry cycle such as nitrogen transformation and functional microorganism in the soil. In the present study, we conducted a 45-day soil microcosm experiment with polystyrene (PS) MPs/NPs and Ag NPs to investigate their combined impact on nitrogen cycling and the bacterial community. The results showed that MPs or NPs exerted limited effects on nitrogen transformation in the soil. The combined effects of PS MPs/NPs and Ag NPs were mainly caused by the presence of Ag NPs. However, PS NPs alleviated the inhibition of anammox and denitrification induced by Ag NPs via upregulating anammox-related genes and elevating nitrate and nitrite reductase activities. PS MPs + Ag NPs treatment significantly reduced bacterial diversity. PS MPs/NPs + Ag NPs increased the relative abundances of denitrifying Cupriavidus by 0.32% and 0.06% but decreased nitrogen-fixing functional microorganisms of Microvirga (by 2.05% and 2.24%), Bacillus (by 0.16% and 0.22%), and Herbaspirillum (by 0.14% and 0.07%) at the genus level compared with Ag NPs alone. The significant downregulation of nitrogen-fixing genes (K02586, K02588, and K02591) was observed in PS MPs/NPs + Ag NPs treatment compared to Ag NPs in the nitrogen metabolism pathway. Moreover, g-Lysobacter and g-Aquimonas were identified as biomarkers in PS MPs + Ag NPs and PS NPs + Ag NPs by LEfSe analysis. Our study sheds the light that changes of functional microorganism abundances contributed to the alteration of nitrogen transformation. Taking the particle size of plastics into account will be helpful to accurately assess the combined ecological risks of plastics and nanomaterial contaminants.

DNA methylation detection technology and plasma-based methylation biomarkers in screening of gastrointestinal carcinoma.

DNA methylation is of paramount importance for the evolution of human cancers. Its high sensitivity and specificity make it a potential biomarker for early cancer screening in the context of an increasing global burden of gastrointestinal (GI) carcinoma. More DNA methylation biomarkers are emerging with the development of liquid biopsy and sensitive DNA methylation detection technology. This review provides an overview of DNA methylation, focusing on the presentation and comparison of 5-methylcytosine detection technologies, and introduces the promising plasma-based cell-free DNA (cfDNA) methylation biomarkers published in recent years for early screening of GI carcinoma. Finally, we summarize and discuss the future of plasma cfDNA methylation markers detection as a clinical tool for early screening of GI carcinoma.

Lay abstract In the context of an increasing global burden of gastrointestinal (GI) carcinoma, early cancer screening is of paramount importance, so there is an urgent need for efficient and reliable potential biomarkers. More biomarkers are emerging with the development of noninvasive test and related detection technologies. This review provides an overview of certain potential biomarkers named DNA methylation, focusing on the presentation and comparison of related detection technologies for this type of biomarkers and introduces the promising plasma-based biomarkers published in recent years for early screening of GI carcinoma. Finally, we summarize and discuss the future of plasma-based biomarkers detection as a clinical tool for early screening of GI carcinoma.

Butorphanol Inhibits the Malignant Biological Behaviors of Ovarian Cancer Cells via Down-Regulating the Expression of TMEFF1.

PURPOSE: An important issue with compounds for treating ovarian cancer is the development of drug resistance and side effects. Butorphanol is a synthetic opioid. Opioids have been shown to promote or prevent tumor growth and metastasis. This research aimed to reveal the affection of Butorphanol on the malignant biological behaviors of ovarian cancer cells. METHODS: Different concentrations of Butorphanol were used to treat ovarian cancer cell lines, ES-2 and SKOV3. Biological functions of cells were performed by CCK-8 assay, colony formation assay, apoptosis analysis, transwell assays and scratch assays. The differences in the transcriptome of the Butorphanol treated and negative control (NC) cells were analyzed by RNA-Seq. RESULTS: Butorphanol treatment significantly inhibited the viability, colony-forming, migration and invasion of ES-2 and SKOV3 cells compared to NC. Furthermore, Butorphanol treatment obviously induced the apoptosis of ES-2 and SKOV3 cells and regulated the expression of apoptosis-related proteins. Additionally, Butorphanol treatment significantly reduced the expression of p-AKT, p-mTOR and P70S6K without affecting the expression of AKT and mTOR in ES-2 and SKOV3 cells. Forty-four genes were identified to up-regulate its expression, while 17 genes were identified to down-regulate its expression in Butorphanol-treated cells. Among them, TMEFF1 was found to be significantly down-regulated in Butorphanol-treated cells. Additionally, the restoration of TMEFF1 expression complemented the inhibitory effect of Butorphanol treatment on cell proliferation and invasion. CONCLUSION: In conclusion, Butorphanol is a compound with potential to treat ovarian cancer. TMEFF1 may play a key role in inhibiting the malignant proliferation and metastasis of Butorphanol treatment on ovarian cancer cells.

E2F1 transactivates IQGAP3 and promotes proliferation of hepatocellular carcinoma cells through IQGAP3-mediated PKC-alpha activation.

For decades, E2F1 has been recognized as a retinoblastoma protein (RB) binding transcription factor that regulates the cell cycle. E2F1 binds preferentially to RB and accelerates the cell cycle in most cancer cells. However, it is thought that E2F1 modulates cell proliferation in other ways as well. Herein, it has been discovered that in pathological tissues derived from hepatocellular carcinoma (HCC) patients, E2F1 correlates positively with IQGAP3 and that both of these factors are highly expressed (N = 164, R = 0.6716). In addition, a high level of E2F1 or IQGAP3 predicted poor survival in HCC patients. Further study determined that E2F1 transactivates IQGAP3, the GTPase binding protein in MHCC-97H cells. Co-immunoprecipitation analysis indicated that IQGAP3 interacts with PKCδ and competitively inhibits the interaction between PKCδ and PKCα, resulting in phosphorylation of PKCα activation and promotion of cell proliferation. This study reveals that highly expressed E2F1 not only transactivates cell-cycle-related factors but also promotes HCC proliferation by activating the phosphorylation of PKCα.

Cigarette smoke condensate could promote human bronchial epithelial BEAS-2B cell migration through shifting neprilysin trafficking.

AIM OF STUDY: Recent studies have suggested neprilysin (NEP) play a key role in cigarette smoke-induced nonsmall-cell lung carcinoma; however, the detailed mechanism was still unclear. Here, we employed in vitro human bronchial epithelial BEAS-2B cells to investigate whether and how NEP involved in cigarette smoke condensate (CSC)-induced cancer occurrence. MATERIALS AND METHODS: In vitro MTT and transwell assay was applied. Live cell imaging and staining were also employed. RESULTS: In vitro data showed that CSC could increase BEAS-2B cell migration while NEP shRNA could block CSC-induced BEAS-2B cell hypermigration. By biotination and live cell staining, we found that after CSC treatment, cell surface NEP was increased while internalization trafficking was shifted from late endosome/lysosome pathway to recycling pathway. Finally, we found that surface NEP could bind to p120 catenin (p120ctn) for lysosome destination turnover while CSC treatment could change p120ctn membrane/cytosome distribution. Loss of p120ctn will subsequently change NEP trafficking and finally, increase its membrane distribution with a phenocopy manner as CSC. CONCLUSION: These data indicated under CSC treatment; losing of membrane p120ctn could upregulate surface NEP protein level and thus facilitate BEAS-2B cell migration.