Reference-free calibration method for asynchronous rotation in robotic CT.

BACKGROUND: Geometry calibration for robotic CT system is necessary for obtaining acceptable images under the asynchrony of two manipulators. OBJECTIVE: We aim to evaluate the impact of different types of asynchrony on images and propose a reference-free calibration method based on a simplified geometry model. METHODS: We evaluate the impact of different types of asynchrony on images and propose a novel calibration method focused on asynchronous rotation of robotic CT. The proposed method is initialized with reconstructions under default uncalibrated geometry and uses grid sampling of estimated geometry to determine the direction of optimization. Difference between the re-projections of sampling points and the original projection is used to guide the optimization direction. Images and estimated geometry are optimized alternatively in an iteration, and it stops when the difference of residual projections is close enough, or when the maximum iteration number is reached. RESULTS: In our simulation experiments, proposed method shows better performance, with the PSNR increasing by 2%, and the SSIM increasing by 13.6% after calibration. The experiments reveal fewer artifacts and higher image quality. CONCLUSION: We find that asynchronous rotation has a more significant impact on reconstruction, and the proposed method offers a feasible solution for correcting asynchronous rotation.

Sparse-view Spectral CT Reconstruction and Material Decomposition based on Multi-channel SGM.

In medical applications, the diffusion of contrast agents in tissue can reflect the physiological function of organisms, so it is valuable to quantify the distribution and content of contrast agents in the body over a period. Spectral CT has the advantages of multi-energy projection acquisition and material decomposition, which can quantify K-edge contrast agents. However, multiple repetitive spectral CT scans can cause excessive radiation doses. Sparse-view scanning is commonly used to reduce dose and scan time, but its reconstructed images are usually accompanied by streaking artifacts, which leads to inaccurate quantification of the contrast agents. To solve this problem, an unsupervised sparse-view spectral CT reconstruction and material decomposition algorithm based on the multi-channel score-based generative model (SGM) is proposed in this paper. First, multi-energy images and tissue images are used as multi-channel input data for SGM training. Secondly, the organism is multiply scanned in sparse views, and the trained SGM is utilized to generate multi-energy images and tissue images driven by sparse-view projections. After that, a material decomposition algorithm using tissue images generated by SGM as prior images for solving contrast agent images is established. Finally, the distribution and content of the contrast agents are obtained. The comparison and evaluation of this method are given in this paper, and a series of mouse scanning experiments are carried out to verify the effectiveness of the method.

Involvement of gut microbiota recovery and autophagy induction in Youhua Kuijie Formula's protection against experimental ulcerative colitis.

Ulcerative colitis (UC) is characterized by overactive inflammatory response, impaired intestinal mucosal barrier and disrupted gut microbiota. Youhua Kuijie formula is a classic empirical prescription based on the pathogenesis of UC. The present study was designed to verify the protective effect of Youhua Kuijie Formula on DSS-induced UC in mice and uncover the related mechanism. Youhua Kuijie Formula were orally administrated to UC mice induced by DSS dissolved in drinking water for ten days. The protective effect of Youhua Kuijie Formula was evidenced by reduced pathological symptoms accompanied by palliative inflammatory response and relatively intact intestinal barrier. The data from 16S rRNA gene sequencing and GC-MS untargeted metabolomics indicated that the supplement of Youhua Kuijie Formula restructured gut microbiota community structure, and thereby modulated the metabolic profiles in UC mice. The analysis of pathway enrichment analysis suggested the major alterations in metabolic pathway were related to protein digestion and absorption. Besides, the results of the following experiments suggested that Youhua Kuijie Formula treatment increased adenosine monophosphate-activated protein kinase (AMPK) activation, decreased mechanistic target of rapamycin (mTOR) phosphorylation, and thereby reversing autophagy deficiency in the intestinal tract of UC mice. Collectively, our results demonstrated that the regulation of AMPK/mTOR was involved in Youhua Kuijie Formula administration mediated protective effect on UC.

Pathogenomics model for personalized medicine in cervical cancer: Cross-talk of gene expressions and pathological images related to oxidative stress.

An increasing number of studies have shown that oxidative stress plays an important role in the development and progression of cancer. Cervical cancer (CC) is a disease of unique complexity that tends to exhibit high heterogeneity in molecular phenotypes. We aim here to characterize molecular features of cervical cancer by developing a classification system based on oxidative stress-related gene expression profiles. In this study, we obtained gene expression profiling data for cervical cancer from the TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) (GSE44001) databases. Oxidative stress-related genes used for clustering were obtained from GeneCards. Patients with cervical cancer were divided into two subtypes (C1 and C2) by non-negative matrix factorization (NMF) classification. By performing Kaplan-Meier survival analysis, differential expression analysis, and gene set enrichment analysis (GSEA) between the two subtypes, we found that subtype C2 had a worse prognosis and was highly enriched for immune-related pathways as well as epithelial-mesenchymal transition (EMT) pathways. Subsequently, we performed metabolic pathway analysis, gene mutation landscape analysis, immune microenvironment analysis, immunotherapy response analysis, and drug sensitivity analysis of the two isoforms. The results showed that the isoforms were significantly different between metabolic pathway enrichment and the immune microenvironment, and the chromosomes of subtype C1 were more unstable. In addition, we found that subtype C2 tends to respond to treatment with anti-CTLA4 agents, a conclusion that coincides with high chromosomal variation in C1, as well as C2 enrichment of immune-related pathways. Then, we screened 10 agents that were significantly susceptible to C2 subtype. Finally, we constructed pathogenomics models based on pathological features and linked them to molecular subtypes. This study establishes a novel CC classification based on gene expression profiles of oxidative stress-related genes and elucidates differences between immune microenvironments between CC subtypes, contributing to subtype-specific immunotherapy and drug therapy.

Single-Molecule Force Spectroscopy of Deoxyribonucleic Acid and Deoxyribonucleic Acid Polymerase Activity Impacted by Alkylating Agents.

DNA alkylating agents are widely used in anticancer pharmacology. Although shown to induce cross-linking and/or methylation of DNA, how they affect the mechanical properties of DNA and activity of DNA enzymes remains to be elucidated. Here, we perform single-molecule optical tweezer experiments on DNA treated with alkylating agents, including melphalan, cisplatin, and dacarbazine. While all three drugs induce a significant increase of overstretching force and a reduction of hysteresis, suggesting stabilization of DNA against shearing forces, their effects on elasticity of DNA were quite different, with the largest change in persistence length induced by cisplatin. Furthermore, we find that these alkylating-agent-induced changes on DNA have different effects on processivity of DNA polymerase, with melphalan and cisplatin showing significantly reduced activity and dacarbazine showing little effect. Overall, our results provide new insights into the effects for these alkylating agents, which could potentially facilitate a better design of related drugs.

Detector shifting and deep learning based ring artifact correction method for low-dose CT.

BACKGROUND: In x-ray computed tomography (CT), the gain inconsistency of detector units leads to ring artifacts in the reconstructed images, seriously destroys the image structure, and is not conducive to image recognition. In addition, to reduce radiation dose and scanning time, especially photon counting CT, low-dose CT is required, so it is important to reduce the noise and suppress ring artifacts in low-dose CT images simultaneously. PURPOSE: Deep learning is an effective method to suppress ring artifacts, but there are still residual artifacts in corrected images. And the feature recognition ability of the network for ring artifacts decreases due to the effect of noise in the low-dose CT images. In this paper, a method is proposed to achieve noise reduction and ring artifact removal simultaneously. METHODS: To solve these problems, we propose a ring artifact correction method for low-dose CT based on detector shifting and deep learning in this paper. Firstly, at the CT scanning stage, the detector horizontally shifts randomly at each projection to alleviate the ring artifacts as front processing. Thus, the ring artifacts are transformed into dispersed noise in front processed images. Secondly, deep learning is used for dispersed noise and statistical noise reduction. RESULTS: Both simulation and real data experiments are conducted to evaluate the proposed method. Compared to other methods, the results show that the proposed method in this paper has better effect on removing ring artifacts in the low-dose CT images. Specifically, the RMSEs and SSIMs of the two sets of simulated and experiment data are better compared to the raw images significantly. CONCLUSIONS: The method proposed in this paper combines detector shifting and deep learning to remove ring artifacts and statistical noise simultaneously. The results show that the proposed method is able to get better performance.

A Matching Strategy To Guide Donor Selection for Ulcerative Colitis in Fecal Microbiota Transplantation: Meta-Analysis and Analytic Hierarchy Process.

Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of ulcerative colitis (UC). However, preliminary trials showed that only a subset of patients responded to FMT, and the heterogeneity in donor gut microbiota probably played important roles in patients' responses, implying the significance of matching an appropriate donor to a specified patient. We developed a strategy to build a donor-recipient matching model to guide rational donor selection for UC in FMT. We collected and uniformly reanalyzed 656 fecal 16S rRNA gene sequencing samples (350 from UC patients and 306 from healthy subjects) from 9 studies. Significantly lower α-diversity indexes were observed in UC patients by random effects model. Thirty-four bacterial genera and 34 predicted pathways were identified with significant odds ratios and classification potentials for UC patients. Based on six bacterial indicators, including richness, overall distance, genera, and pathways (beneficial and harmful), the analytic hierarchy process-based donor-recipient matching model was set to rank and select appropriate donors for patients with UC. Finally, the model showed favorable classification powers (>70%) for FMT effectiveness in two previous clinical trials. This study revealed the dysbiosis of fecal bacterial diversity, composition, and predicted pathways of patients with UC by meta-analysis and hereby developed a donor-recipient matching strategy to guide donor selection for UC in FMT. This strategy can also be applied to other diseases associated with gut microbiota. IMPORTANCE Modulation of gut microbiota by FMT from donors has been applied to the treatment of UC and yielded variable effectiveness in clinical trials. One possibility is that this variable effectiveness was related to donor selection, as a patient's response to FMT may rely on the capability of the used donor's microbiota to restore the specific gut disturbances of the patient. However, the biggest issues on the practical level are what should be considered in the selection process and how to set up such a donor-recipient matching model. In this study, we presented a bacterial profile-based donor-recipient matching strategy to guide donor selection for UC in FMT by first meta-analysis of 656 fecal 16S rRNA gene sequencing samples from 9 studies to identify significant indicators and then setting up the model by an analytic hierarchy process. The applicability and accuracy of this model were verified in the data sets from two previous FMT clinical studies. Our data indicate that the donor-recipient matching model built in this study enables researchers to rationally select donors for UC patients in FMT clinical practice, although it needs more samples and prospective trials for validation. The strategy adopted in this study to leverage existing data sets to build donor-recipient matching models for precision FMT is feasible for other diseases associated with gut microbiota.

Design of a Comprehensive Assessment Model for the Stability and Engineering Geology of Slope Based on Improved Convolutional Neural Network.

The geological mechanics, geotechnical characteristics, and hydrogeological conditions of slopes are complex and changeable, so their stability assessment is a complicated system; their traditional engineering geological assessment does not consider the opposition of the system, the uncertainty of performance indicators, and the ambiguity of index classification, being easy to distort results due to the ambiguity. Improved convolutional neural network (CNN) has outstanding advantages in analyzing problems with randomness and fuzziness. It can perform unified numerical processing on slope assessment indicators with precise values, interval values, and qualitative judgment values, making the traditional qualitative description is transformed into quantitative calculation. Therefore, on the basis of summarizing and analyzing previous research works, this paper expounded the research status and significance of the comprehensive assessment model for slope stability and engineering geology; elaborated the development background, current status, and future challenges of the improved CNN; introduced the methods and principles of the model structure, convolutional layer design, and data flow optimization of the improved CNN; performed the assessment index system establishment and index weight determination; established the mathematical assessment model for slope stability; conducted the assessment module design for slope stability based on the improved CNN; analysed the importance of individual factors to the comprehensive engineering geological characteristics; discussed the determination of assessment value of comprehensive unit engineering geological characteristics; explored the assessment module design for slope engineering geology based on the improved CNN; and finally carried out an engineering application and its result analysis. The study results show that the improved CNN can select some universal and objective factors according to the actual conditions of slopes, including topography, stratum lithology, geological structure, atmospheric rainfall, groundwater, engineering activities, setting up factor sets and judgment sets, and making fuzzy inferences. The comprehensive assessment model can use appropriate mathematical methods to judge the pros and cons of slope's stability and engineering geology according to certain principles and standards, and grade the results and identify the most important geological problems. The results of this paper provide a reference for further researches on the design of a comprehensive assessment model for slope stability and engineering geology based on the improved CNN.

A comprehensive approach to stool donor screening for faecal microbiota transplantation in China.

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China. RESULTS: The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time. CONCLUSIONS: DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.

Occurrence and risk assessment of fluoroquinolone antibiotics in reclaimed water and receiving groundwater with different replenishment pathways.

Artificial recharge to groundwater with reclaimed water is considered a promising method to alleviate groundwater depletion and over-exploitation. However, the occurrence of fluoroquinolone antibiotics (FQs) was ubiquitous in wastewater, surface water, groundwater and even drinking water threating human health and ecology. In this study, the occurrence of six selected FQs in reclaimed water effluent and their removal by tertiary treatment units were investigated. The overall removal efficiencies in average of the tertiary treatment processes in Beijing and Changzhou were ranging from 21.2% to 55.2%. Activated carbon exhibited better performance for FQs removal than ozone and biological treatment such as membrane bioreactor, anaerobic-anoxic-oxic and biofilter. The results of two pilot study showed that the impact of reclaimed water to groundwater quality in terms of FQs concentration by direct injection in GBD was stronger than surface spreading in Changzhou, which might be due to the recharge strategy and the physical and chemical characteristics of sediment and aquifer soil. The hazard quotient (HQ) values of ofloxacin (OFL) in reclaimed water was up to 12.54, indicating the extreme eco-toxicological risk, while enrofloxacin (ENR) exhibited medium risk. After recharge with reclaimed water, the HQ values of OFL and ENR in groundwater ranged from low to medium ecological risk to the environment. Thus, the FQs in reclaimed water need to be paid more attention during their reuse for groundwater recharge, especially by direct injection. It is suggested that FQs should be considered in the priority substances lists in standards and guidelines of reclaimed water reuse for groundwater recharge to ensure the safety of groundwater.

Adsorption behavior of three triazole fungicides on polystyrene microplastics.

Environmental pollution caused by microplastics (MPs) and pesticides has become a global challenge, and increasing evidence shows that MPs can adsorb organic pollutants which may affect their distribution and bioavailability. As widely used pesticides, triazole fungicides with potential environmental and human safety risks often coexist with MPs in the environment. Understanding the adsorption behavior is the basis of risk assessment of co-exposure of MPs and triazole fungicides. In this study, the adsorption behavior of three commonly used triazole fungicides on polystyrene (PS) was studied using adsorption test. The influences of PS particle size and environmental factors on adsorption capacity were evaluated, and the adsorption mechanisms were discussed. Results suggested that the adsorption kinetics and isotherm conformed to the Pseudo-second-order and Freundlich model, respectively. The order of adsorption and desorption capacity was hexaconazole (HEX) > myclobutanil (MYC) > triadimenol (TRI), which was positively correlated with LogKow of pesticides. To a certain extent, the decrease in PS particle size and change in solution pH value and increase in salt ion strength all contribute to increasing adsorption capacity. The main mechanisms of adsorption were hydrophobic and electrostatic interactions. MPs can adsorb and may become the source and sink of triazole fungicides in aqueous environments. Our results demonstrate that more attention should be given to the combined water pollution risk of MPs and triazoles fungicides.

STAT1-induced upregulation of LINC00467 promotes the proliferation migration of lung adenocarcinoma cells by epigenetically silencing DKK1 to activate Wnt/ß-catenin signaling pathway.

Long non-coding RNAs (lncRNAs) have been reported as essential regulators in human cancers, including lung adenocarcinoma (LUAD). In the present study, we found that lncRNA long intergenic non-protein coding RNA 467 (LINC00467) was expressed higher in TCGA LUAD samples and predicted poor prognosis in LUAD patients. High expression of LINC00467 was further detected in LUAD cell lines. Functionally, high expression level of LINC00467 promoted LUAD cell proliferation and migration, indicating that LINC00467 exerted oncogenic functions in LUAD progression. Considering the upregulation of LINC00467 in LUAD, we further detected the activator of LINC00467 promoter. Combining with bioinformatics analysis and mechanism experiments, we determined that LINC00467 was activated by STAT1 in LUAD. Moreover, high expression of LINC00467 was found to be associated with the activation of Wnt/ß-catenin signaling pathway. Rescue assays demonstrated that dickkopf WNT signaling pathway inhibitor 1 (DKK1; an inhibitor of Wnt/ß-catenin signaling pathway) and Wnt/ß-catenin signaling involved in DKK1-mediated LUAD cell proliferation and migration. Furthermore, LINC00467 was located in the nucleus of LUAD cell lines and negatively regulated DKK1 in LUAD cells. Mechanistically, we determined that LINC00467 epigenetically silenced DKK1 by recruiting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) to DKK1 promoter. Collectively, we determined that STAT1-induced upregulation of LINC00467 promoted LUAD progression by epigenetically silencing DKK1 to activate Wnt/ß-catenin signaling pathway.

Traditional Chinese Medicine herbs for stopping bleeding from haemorrhoids.

BACKGROUND: Haemorrhoids is a common perianal disease, which often causes haematochezia. Besides a surgical operation or minimally invasive treatment, a variety of traditional Chinese medicinal herbs (TCMHs) have been used to treat bleeding haemorrhoids. OBJECTIVES: To assess the effectiveness of traditional Chinese medicinal herbs for stopping bleeding from haemorrhoids and the adverse effects caused by these herbs. SEARCH STRATEGY: We searched the Cochrane Colorectal Cancer Group Trials Register, Cochrane Central Register of Contolled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CMCD (Chinese Medicine Conference Disc) and CBMD (Chinese Bio-Medicine Disc). SELECTION CRITERIA: All randomised clinical trials (RCTs) of Chinese herbs for bleeding haemorrhoids were included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data, which were analysed using RevMan 5.0 software. We estimated the relative risk for dichotomous data and calculated the weighted mean difference for continuous data. MAIN RESULTS: Nine trials involving 1822 patients with bleeding haemorrhoids were identified. The included trials were generally not of high quality and used one TCMH preparation compared with another TCMH preparation (Type I) (five trials) or western medicines (Type II) (four trials). We could not pool the data to perform a meta-analysis as only two of the included trials used the same intervention or comparison.In the nine trials, TCMHs showed a statistically significant difference for the improvement in the general curative effects or total grade of symptoms in six trials (P < 0.05; P < 0.01), of hematochezia in three trials (P < 0.05; P < 0.001), and of inflammation of perianal mucosa in one trial (P < 0.05). The adverse effects reported were not serious and were scarce. AUTHORS' CONCLUSIONS: This review did not provide strong evidence concerning the effectiveness of TCMHs for stopping bleeding from haemorrhoids. Most of the included studies were of low quality and there was a scarcity of eligible trials and numbers of participants. Limited, weak evidence showed that some herbal formulae, when including Radix Sanguisorbae, Radix Rehmanniae, Fructus Sophorae, Radix Angelicae Sinensis, Radix Scutellariae, etc., may alleviate some symptoms caused by haemorrhoids. These include hematochezia, congestive haemorrhoidal cushions and inflammation of perianal mucosa in the short term. Well-designed clinical trials are required urgently before any confident conclusions can be drawn about the value of TCMHs for stopping bleeding from haemorrhoids.At present, the evidence is not enough that clinical practice should be changed immediately on the basis of these results.

[Effect of KDR recombinant adenovirus containing double suicide gene on the proliferation of human colon adneocarcinoma SW620 cells].

OBJECTIVE: To study the effect of adenovirus (Ad)-mediated fusion gene system driven by the KDR promoter on the proliferation of human colon adenocarcinoma SW620 cells. METHODS: The KDR-expressing SW620 cells and LS174T cells not expressing KDR were both infected with AdEasy-KDR-CDglyTK followed by treatment with the prodrugs 5-FC and/or ganciclovir at different concentrations. The effect of the transfection on the cell proliferation was evaluated. RESULTS: The expression of green fluorescent protein (GFP) was observed in 95% of the infected SW620 and LS174T cells with a multiplicity of infection (MOI) of 100. Significant difference was not founded in the growth of SW620 and LS174T cells with or without the transfection. The infected SW620 cells exhibit high sensitivity to the prodrugs, but the infected LS174T cells did not (P<0.01). The CDglyTK fusion gene produced much stronger killing effect of on the target cells than either of the single suicide genes (P<0.01). CONCLUSION: CDglyTK fusion gene system driven by the KDR promoter selectively kills the KDR-CDglyTK SW620 cells and inhibits the cell proliferation.

[The relation of metastasis and prognosis with transforming growth factor-beta1 and E-cadherin expression in supraglottic larynx squamous cell carcinoma].

OBJECTIVE: To study the expression of transforming growth factor-beta1 (TGF-beta1) and E-cadherin (E-cd) in Supraglottic larynx squamous cell carcinoma (SGLSCC) and the correlation with lymph node metastasis of neck. METHOD: The expression of TGF-beta1 and E-cd were studied in 60 cases of samples with SGLSCC and 10 cases of normal laryngeal mucosa by immunohistochemical staining (SABC method). They connected with clinical and followed data were analyzed. RESULT: Among 60 cases of human SGLSCC, 81.7% (49/60), 70.0% (42/60) were respectively defined as TGF-beta1 and E-cd - positive. Among 10 cases of normal laryngeal mucosa, 20.0% (2/10) 90.0% (9/10) were respectively defined as TGF-beta1 and E-cd - positive. There is a positive correlation between the expression of TGF-beta1 and the groups of lymph node metastasis, pathologic grade and clinical stage. However, there is a negative correlation between the expression of E-cd and the groups of lymph node metastasis, pathologic grade and clinical stage. The expression of the two indexes were significantly related to lymph node metastasis and not related to the age and sex of the patients,as well as the size of tumors. Although the two indexes were not concerted, they were inversely correlated with each other. E-cd expression was directly correlated with the survival functions of operated patients. CONCLUSION: The expression of TGF-beta1 and E-cd are correlated with lymph node metastasis in SGLSCC. There was negatively related to the two indexes. The two indexes may become the marker to predict the lymph node metastasis in SGLSCC, and E-cd may become the marker to judge the prognosis of SGLSCC.