Colorectal image analysis for polyp diagnosis.

Colorectal polyp is an important early manifestation of colorectal cancer, which is significant for the prevention of colorectal cancer. Despite timely detection and manual intervention of colorectal polyps can reduce their chances of becoming cancerous, most existing methods ignore the uncertainties and location problems of polyps, causing a degradation in detection performance. To address these problems, in this paper, we propose a novel colorectal image analysis method for polyp diagnosis via PAM-Net. Specifically, a parallel attention module is designed to enhance the analysis of colorectal polyp images for improving the certainties of polyps. In addition, our method introduces the GWD loss to enhance the accuracy of polyp diagnosis from the perspective of polyp location. Extensive experimental results demonstrate the effectiveness of the proposed method compared with the SOTA baselines. This study enhances the performance of polyp detection accuracy and contributes to polyp detection in clinical medicine.

Deciphering the metabolic heterogeneity of hematopoietic stem cells with single-cell resolution.

Metabolic status is crucial for stem cell functions; however, the metabolic heterogeneity of endogenous stem cells has never been directly assessed. Here, we develop a platform for high-throughput single-cell metabolomics (hi-scMet) of hematopoietic stem cells (HSCs). By combining flow cytometric isolation and nanoparticle-enhanced laser desorption/ionization mass spectrometry, we routinely detected >100 features from single cells. We mapped the single-cell metabolomes of all hematopoietic cell populations and HSC subpopulations with different division times, detecting 33 features whose levels exhibited trending changes during HSC proliferation. We found progressive activation of the oxidative pentose phosphate pathway (OxiPPP) from dormant to active HSCs. Genetic or pharmacological interference with OxiPPP increased reactive oxygen species level in HSCs, reducing HSC self-renewal upon oxidative stress. Together, our work uncovers the metabolic dynamics during HSC proliferation, reveals a role of OxiPPP for HSC activation, and illustrates the utility of hi-scMet in dissecting metabolic heterogeneity of immunophenotypically defined cell populations.

Efficacy and safety of subthreshold micropulse laser in the treatment of acute central serous chorioretinopathy.

AIM: To analyze the efficacy and safety of subthreshold micropulse laser (SML) in the treatment of acute central serous chorioretinopathy (CSC). METHODS: This is a retrospective case analysis study. Totally 58 eyes of 58 patients were enrolled, and they were divided into different groups. And 39 patients were treated with SML (SML group) and 19 patients were only observed (observation group). The follow-up period was 3mo after diagnosis. The best corrected visual acuity (BCVA), central retinal thickness (CRT), superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), the superficial and deep foveal avascular zone (FAZ) area, retinal light sensitivity (RLS), perfusion area of choroidal capillary layer (CCL), subfoveal choroidal thickness (SFCT) and fundus autofluorescence (FAF) were investigated. RESULTS: The BCVA, CRT, SRVD, DRVD, the superficial and deep FAZ area, RLS, SFCT of SML group were significantly improved at 3mo (all P<0.05). In the observation group, only CRT, DRVD and SFCT were improved (all P<0.05). Other research items in the observation group were not significantly different from baseline (all P>0.05). At the last follow-up, the BCVA and RLS in the SML group were better than those in the observation group, and CRT was lower, SRVD and DRVD, perfusion area of CCL were larger (all P<0.05). On FAF, no change of treatment spots was found after treatment. No structural laser damage was observed on optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA), and no choroidal neovascularization was observed. CONCLUSION: SML treatment of acute CSC can improve BCVA, RLS, and perfusion area of CCL, reduce CRT, increase SRVD and DRVD, and is safe.

A covalent organic framework-based nanoreactor for enhanced photothermal therapy via inhibiting intracellular heat defense systems.

Herein, we report an indocyanine green (ICG)-decorated and glucose oxidase (GOx)-loaded nanoscale composite COF material via a stepwise post-synthetic modification. The obtained GOx@COF-ICG can achieve synergistic inhibition of intracellular heat defense systems through starvation therapy to enhance photothermal therapy of tumors.

A reactive oxygen species-responsive covalent organic framework for tumor combination therapy.

Herein, we report the first reactive oxygen species (ROS)-responsive dithioketal-linked covalent organic framework (COF) for synergetic chemotherapy and photodynamic therapy (PDT) of cancer. The singlet oxygen (1O2)-responsive COF dissociation and DC_AC50 drug release complement and reinforce each other to allow an efficient combination of PDT and chemotherapy.

A biodegradable covalent organic framework for synergistic tumor therapy.

Stimulus-responsive biodegradable nanocarriers with tumor-selective targeted drug delivery are critical for cancer therapy. Herein, we report for the first time a redox-responsive disulfide-linked porphyrin covalent organic framework (COF) that can be nanocrystallized by glutathione (GSH)-triggered biodegradation. After loading 5-fluorouracil (5-Fu), the generated nanoscale COF-based multifunctional nanoagent can be further effectively dissociated by endogenous GSH in tumor cells, releasing 5-Fu efficiently to achieve selective chemotherapy on tumor cells. Together with the GSH depletion-enhanced photodynamic therapy (PDT), an ideal synergistic tumor therapy for MCF-7 breast cancer via ferroptosis is achieved. In this research, the therapeutic efficacy was significantly improved in terms of enhanced combined anti-tumor efficiency and reduced side effects by responding to significant abnormalities such as high concentrations of GSH in the tumor microenvironment (TME).

Correlation Analysis between Uric Acid and Metabolic Syndrome in the Chinese Elderly Population: A Cross-Sectional Study.

Background: Currently, both metabolic syndrome and hyperuricaemia have attracted extensive attention in public health. The correlation between uric acid and metabolic syndrome is controversial. Research on the relationship between uric acid and metabolic syndrome in community-dwelling elderly people is relatively lacking. The purpose of this study is to explore the relationship between uric acid and metabolic syndrome in the community-dwelling elderly people. Design: Cross-sectional study. Methods: We collected the physical examination data of 1,267 elderly people in Gutian community in Wuhan and used SPSS IBM 25.0 for data analysis. Correlation and logistic regression analyses were performed, and ROC curves were drawn. Results: The uric acid level of the nonmetabolic syndrome group was lower than that of the metabolic syndrome group (337.31 vs. 381.91 µmol/L; P < 0.05). Uric acid was positively correlated with systolic blood pressure (r = 0.177, P < 0.001), diastolic blood pressure (r = 0.135, P < 0.001), body mass index (r = 0.234, P < 0.001), waist circumference (r = 0.283, P < 0.001), and triglycerides (r = 0.217, P < 0.05). High-density lipoprotein cholesterol (r = -0.268, P < 0.001) showed the opposite trend. Logistic regression analysis results suggested that uric acid is a risk factor for metabolic syndrome. The result is described as exp (B) and 95% CI (1.003 [1.001, 1.005]). Based on the receiver operating characteristic curve, we found that the area under the curve of uric acid to diagnose metabolic syndrome was 0.64 (sensitivity: 79.3%, specificity: 45.1%). Conclusion: We observed an association between uric acid levels and metabolic syndrome in the elderly Chinese population. The best threshold value for uric acid in predicting metabolic syndrome diagnosis was 314.5 µmol/l.

Orosomucoid: a promising biomarker for the assessment of exercise-induced fatigue triggered by basic combat training.

BACKGROUND: Orosomucoid (ORM) is a positive acute phase protein verified to be upregulated in various forms of exercise-induced fatigued (EIF) rodents. However, its association with EIF among human beings remained unknown. This study aimed to explore the association between serum ORM and EIF triggered by military basic combat training (BCT). METHODS: The degree of EIF were measured by Borg's Rating of Perceived Exertion Scale (Borg-RPE-Scale®) as RPE score after BCT. Fifty-three male recruits were classified into three groups according to the RPE score: (1) group 1 (slight fatigue group): RPE score after BCT < 13; (2) group 2 (moderate fatigue group): RPE score after BCT = 13 or 14; (3) group 3 (severe fatigue group): RPE score after BCT > 14. The levels of blood ORM, lactate (LAC), cortisol and C-reactive protein (CRP) were determined before and after BCT. The diagnostic value of ORM was evaluated by receiver operating characteristic (ROC) curve analysis and logistic regression. RESULTS: After BCT, the level of LAC, CRP, and cortisol increased among all groups, but the changes had no significant between-group difference (all p > 0.05). The level of ORM had a specific significant increase in group 3 (p = 0.039), and the changes of ORM (ΔORM) had significant difference among groups (p = 0.033). ROC curve analysis showed that the estimated area under ROC curve for ΔORM was 0.724 (p = 0.009) with the recommended optimal cut-off value as 0.2565 mg/mL. Logistic analysis showed that recruits with ΔORM ≥ 0.2565 mg/mL had higher odds for suffering from severe EIF, 5.625 times (95% CI 1.542-20.523, p = 0.009) as large as those with ΔORM < 0.2565 mg/mL. CONCLUSION: ORM might be a promising biomarker of severe EIF triggered by BCT among male recruits. Its potential optimal cut-off value regarding ΔORM was recommended to be 0.2565 mg/mL.

A metal-organic cage-based nanoagent for enhanced photodynamic antitumor therapy.

Herein, we report, for the first time, a Pd6L8(NO3)5.4(ICG)6.6 (ICG = indocyanine green) cage-based hexagonal nanoplate (3) via a combined nanoprecipitation and solid-state anion-exchange approach. Nanoplate 3 possesses enhanced near-infrared (NIR) light-triggered 1O2 generation, high cellular uptake selective lysosome-targeting ability, and, consequently, excellent antineoplastic activity.

MicroRNA124-IL6R Mediates the Effect of Nicotine in Inflammatory Bowel Disease by Shifting Th1/Th2 Balance Toward Th1.

Epidemiological investigations have shown that smoking ameliorates ulcerative colitis (UC) but exacerbates Crohn's disease (CD), diseases that feature a Th2-mediated and Th1-mediated response, respectively. Cigarette extracts, especially nicotine, affect the Th1/Th2 balance. We previously reported that nicotine protects against mouse DSS colitis (similar to UC) by enhancing microRNA-124 (miR-124) expression. Intriguingly, elevation of miR-124 in CD is reported to aggravate the disease. Here we investigate the dual regulation of miR-124 in inflammatory bowel diseases (IBDs), which may explain the similar bidirectional regulation of tobacco. We found that overexpressed miR-124 protected against mouse DSS-induced colitis with a Th1 polarization in peripheral blood lymphocytes and colon tissues, which was also found in human peripheral blood lymphocytes. Conversely, miR-124 knockdown worsened DSS murine colitis with a Th2 polarization. Moreover, knockdown of miR-124 could eliminate the polarization toward Th1 after nicotine treatment, suggesting that miR-124 mediates the effect of nicotine on the Th1/Th2 balance. In addition, interference of IL-6R, which is a downstream target of miR-124, could remarkably weaken the Th1 polarization induced by miR-124. Taken together, these results suggest that nicotine shifts the balance of Th1/Th2 toward Th1 via a miR-124-mediated IL-6R pathway, which might explain its dual role in IBDs.

An Early Intestinal Cancer Prediction Algorithm Based on Deep Belief Network.

The incidence of colorectal cancer (colorectal cancer, CRC) in China has increased in recent years, and its mortality rate has become one of the highest among all cancers. CRC also increasingly affects people's health and quality of life, and the workloads of medical doctors have further increased due to the lack of sufficient medical resources in China. The goal of this study was to construct an automated expert system using a deep learning technique to predict the probability of early stage CRC based on the patient's case report and the patient's attributes. Compared with previous prediction methods, which are either based on sophisticated examinations or have high computational complexity, this method is shown to provide valuable information such as suggesting potentially important early signs to assist in early diagnosis, early treatment and prevention of CRC, hence helping medical doctors reduce the workloads of endoscopies and other treatments.

Role of acute-phase protein ORM in a mice model of ischemic stroke.

The only Food and Drug Administration-approved treatment for acute ischemic stroke is tissue plasminogen activator, and the discovery of novel therapeutic targets is critical. Here, we found orosomucoid (ORM), an acute-phase protein mainly produced by the liver, might act as a treatment candidate for an ischemic stroke. The results showed that ORM2 is the dominant subtype in mice normal brain tissue. After middle cerebral artery occlusion (MCAO), the level of ORM2 is significantly increased in the ischemic penumbra compared with the contralateral normal brain tissue, whereas ORM1 knockout did not affect the infarct size. Exogenous ORM could significantly decrease infarct size and neurological deficit score. Inspiringly, the best administration time point was at 4.5 and 6 hr after MCAO. ORM could markedly decrease the Evans blue extravasation, and improve blood-brain barrier-associated proteins expression in the ischemic penumbra of MACO mice and oxygen-glucose deprivation (OGD)-treated bEnd3 cells. Meanwhile, ORM could significantly alleviate inflammation by inhibiting the production of interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor α (TNF-α), reduce oxidative stress by improving the balance of malondialdehyde (MDA) and superoxide dismutase (SOD), inhibit apoptosis by decreasing caspase-3 activity in ischemic penumbra of MCAO mice and OGD-treated bEnd.3 cells. Because of its protective role at multiple levels, ORM might be a promising therapeutic target for ischemic stroke.

Role of gastroscopic biopsy of gastric ulcer margins and healed sites in the diagnosis of early gastric cancer: A clinical controlled study of 513 cases.

The present case study aimed to evaluate the effect of gastroscopic biopsy of gastric ulcer margins and healed sites in the diagnosis of early gastric cancer. A total of 513 patients who were diagnosed with gastric ulcers using gastroscopy between January 1999 and December 2013 were included in the present study and were divided into either the experimental or the control group. In the control group, samples were only taken from the ulcer margin, whereas in the experimental group samples were taken from the ulcer margin and from the ulcer base. In the experimental group, a routine biopsy of the ulcer margin was performed on first examination, and recheck by gastroscopy was performed from the second week. For ulcers that remained unhealed, a biopsy of the ulcer margin was subsequently conducted; however, for healed or almost healed ulcers, a biopsy of the ulcer base was conducted. The duration of follow-up by gastroscopy ranged between 1 week and 24 months. For the control group, a biopsy of the ulcer margin was conducted using the conventional method. The detection rate of the experimental group was 3.88% (9/232), with 4 cases of gastric cancer confirmed from examinations of the ulcer base. The detection rate of the control group was 1.07% (3/281), which was significantly decreased compared with that of the experimental group (P=0.0345). Overall, patients who underwent regular follow-up gastroscopy following treatment exhibited a markedly increased detection rate of early gastric cancer, suggesting that early cancer may occur in healed gastric ulcer sites.

[Combined Process of DNBF-O3-GAC for Nitrogen and Phosphorus and Metabolite Advanced Removal].

To improve the quality of the tailings water from a wastewater treatment plant (WWTP), a denitrification biofilter (DNBF) with a composite filler composed of a new slow-release organic-carbon source (SOC-F), sponge iron, and activated carbon was tested. Studies were conducted in the combined process of DNBF-O3-GAC to explore the efficiency of the advanced removal of nitrogen, phosphorus, and microbial metabolite by using synthetic effluent made from running water and chemicals. Corresponding comparative studies were conducted by using the secondary effluent from the WWTP. The microbial population structure in the biofilm of the denitrification biofilter was analyzed by adopting MiSeq high-throughput sequencing technologies. The results indicated that the combination process achieved high efficiency removal of nitrogen, phosphorus, and microbial metabolite. The average removal rate of NO3--N in the simulated and actual water period reached 88.87% and 79.99%, respectively; the average removal rate of TP reached 87.67% and 65.51%, respectively; and the average removal rate of UV254 reached 45.51% and 49.23%, respectively. Each processing unit had different functions. The changes in NO3--N, TN, TP, and TFe mainly occurred in the denitrification biofilter, and the removal of UV254 and the change in the three-dimensional fluorescence intensity mainly occurred in the ozone-activated carbon reactor. The cluster analysis at the genus level indicated that the denitrification system had sulfur autotrophic denitrifying bacteria and heterotrophic denitrifying bacteria. Sulfur autotrophic denitrification increased obviously in the actual water period when relatively lack of carbon sources, and the proportion of Thiobacillus increased from 7.44% to 29.62%. The complementary effect of sulfur autotrophic denitrification and heterotrophic denitrification had extended the use of the new slow-release carbon source.

Estrogen weakens muscle endurance via estrogen receptor-p38 MAPK-mediated orosomucoid (ORM) suppression.

Gender differences in fatigue manifest as females being more prone to feel exhaustion and having lower muscle endurance. However, the mechanisms of these effects remain unclear. We investigated whether orosomucoid, an endogenous anti-fatigue protein that enhances muscle endurance, is involved in this regulation. Female rats exhibited lower muscle endurance, and this gender difference disappeared in orosomucoid-1-deficient mice. Female rats also exhibited weaker orosomucoid induction in serum, liver and muscle in response to fatigue compared with male rats. Ovariectomy elevated orosomucoid levels and increased swimming time, and estrogen replenishment reversed these effects. Exogenous estrogen treatment in male and female mice produced opposite effects. Estrogen decreased orosomucoid expression and its promoter activity in C2C12 muscle and Chang liver cells in vitro, and estrogen receptor or p38 mitogen-activated protein kinase blockade abolished this effect. Therefore, estrogen negatively regulates orosomucoid expression that is responsible for the weaker muscle endurance in females.

Association of gender-specific risk factors in metabolic and cardiovascular diseases: an NHANES-based cross-sectional study.

In the present cross-sectional study, based on National Health and Nutrition Examination Survey (NHANES, 2007-2010) cohorts, various risk factors for metabolic syndrome (MetS) and cardiovascular diseases (CVDs) were analyzed (n=12,153). The variables analyzed include, demographics, comorbidities associated with MetS or CVD, behavioral and dietary factors, while the primary endpoints were the prevalence of MetS and CVD. The prevalence of MetS and CVD was slightly higher in males as compared with females (42.50% and 7.65% vs 41.29% and 4.13%, respectively). After controlling for confounding factors, advanced age, family history of diabetes mellitus (DM), overweight, and obesity were significantly associated with the likelihood of MetS, irrespective of gender differences. In males, the diagnosis of prostate cancer and regular smoking were additional risk factors of MetS, whereas, advanced age, family history of heart attack or angina, health insurance coverage, diagnosis of rheumatoid arthritis or depression, obesity and low calorie intake were identified as risk factors for CVD. In addition to the above risk factors, higher physical activity and vitamin D insufficiency were also found to increase the risk of CVD in females. Furthermore, obesity was a higher risk factor for MetS than CVD. Emerging risk factors for CVD identified in this study has major clinical implications. Of interest is the correlation of higher physical activity and the risk of CVD in women and the role of depression and lower calorie intake in general population.

Muscle fatigue: general understanding and treatment.

Muscle fatigue is a common complaint in clinical practice. In humans, muscle fatigue can be defined as exercise-induced decrease in the ability to produce force. Here, to provide a general understanding and describe potential therapies for muscle fatigue, we summarize studies on muscle fatigue, including topics such as the sequence of events observed during force production, in vivo fatigue-site evaluation techniques, diagnostic markers and non-specific but effective treatments.

[Preparation and Phosphorus Removal Mechanism of Highly Efficient Phosphorus Adsorbent Mg/Al-LDO].

Aiming at the problem of phosphorus removal in water, Mg/Al-layered double hydroxides (Mg/Al-LDHs) were synthesized via optimized constant pH co-precipitation method, and highly efficient phosphorus adsorbent Mg/Al-layered double oxide(Mg/Al-LDO) was obtained when it was calcined at high temperature. Based on the adsorption characteristics of phosphorus removal, the study combined Zeta potential, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) to analyze the changes of isoelectric point, crystal structure and functional group before and after adsorption. In addition, Mg/Al-LDO of phosphorus adsorption mechanism was discussed. The results indicated that using the optimized co-precipitation method in the conditions of Mg/Al=2:1, calcination temperature 450℃, and calcination time 2 h, the Mg/Al-LDO adsorption capacity of phosphate was the best, and the maximum adsorption capacity could reach 176.94 mg·g-1, which was basically consistent with the theoretical adsorption capacity of 191.57 mg·g-1, far higher than those of Mg/Al-LDHs and other phosphorus adsorbents. The results showed that the experimental data has the best fitting result with pseudo-second-order kinetics model. The adsorption process was consistent with Langmuir adsorption isotherm model. The results of Zeta potential, XRD and FTIR showed that phosphorus adsorption of Mg/Al-LDO was accomplished co-operatively by electrostatic attraction, anion in layer, ions exchange, and surface co-ordination.

[Effects of Temperature on the Characteristics of Nitrogen and Phosphorus Removal and Microbial Community in SCSC-S/Fe].

In order to investigate the effect of temperature on the cellulose-degrading bacteria and denitrifying bacteria, the denitrification and phosphorus removal of solid carbon source of cellulose corncob+sulfur/sponge iron nitrogen and phosphorus removal composite system, abbreviated as SCSC-S/Fe, was analyzed under different temperature conditions, and the surface structure and microbial properties of corncob before and after reaction were analyzed by scanning electron microscope (SEM) and MiSeq high-throughput sequencing technologies. The results indicated that when temperature increased from 15, 20, 25 to 30℃, the average TN removal rate of the system increased from 78.88% to 92.70%, the average removal rate of TP increased from 82.58% to 89.15%;microbial properties showed that the surface reaction after corncob was dominated by spherical and rod-shaped microorganisms; the proportion of cellulose-degrading bacteria was 11.01% higher at 30℃ than 20℃, and the proportion of denitrifying bacteria decreased by 21.26%. It can be seen that the cellulose -degrading bacteria were more sensitive to the temperature than the denitrification bacteria, and more obviously affected by the temperature.

Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3.

Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis, the underlying mechanisms remain not well understood. Our previous finding that nicotine inhibits inflammatory responses through inducing miR-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine against UC. Our present study found that miR-124 expression is upregulated in colon tissues from UC patients and DSS colitis mice. Nicotine treatment further augmented miR-124 expression in lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells. Moreover, knockdown of miR-124 significantly diminished the beneficial effect of nicotine on murine colitis and IL-6-treated Caco-2 colon epithelial cells. Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6 treated Caco-2 cells and Jurkat human T lymphocytes, in which miR-124 knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine's protective effect in this model. These data indicate that nicotine exerts its protective action in UC through inducing miR-124 and inhibiting STAT3, and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC. KEY MESSAGE: Nicotine upregulates miR-124 expression in ulcerative colon tissues and cells. MiR-124 is required for the protective role of nicotine in DSS colitis mice and epithelial cells. The protective effect of nicotine in murine DSS colitis depends on blocking STAT3 activation. MiR-124 mediates the inhibitory role of nicotine on STAT3/p-STAT3. Targeting miR-124 and STAT3 represents a novel approach for treating ulcerative colitis.