Towards Semi-Autonomous Colon Screening Using an Electromagnetically Actuated Soft-Tethered Colonoscope Based on Visual Servo Control.

OBJECTIVE: Conventional colonoscopy using a flexible colonoscope remains two major limitations, including patient discomfort and difficult manipulations for surgeons. Robotic colonoscopes have been developed to conduct colonoscopy in a patient-friendly manner. However, most robotic colonoscopes still maintain nonintuitive and difficult manipulations, which limits their clinical applications. In this paper, we demonstrated visual servo-based semi-autonomous manipulations of an electromagnetic actuated soft-tethered (EAST) colonoscope, which aims to lower difficulties of robotic colonoscope manipulations. METHODS: Kinematic modeling of EAST colonoscope is conducted, with an adaptive visual servo controller established. Template matching method and a lumen and polyp detection model are developed to enable semi-autonomous manipulations, including region-of-interest automatic tracking and autonomous navigation with automatic polyp detection. RESULTS: The EAST colonoscope demonstrates visual servoing with an average convergence time of around 2.5 s and performs disturbance rejection within 3.0 s. Semi-autonomous manipulations were conducted in both a commercialized colonoscopy simulator and an ex-vivo porcine colon to show the efficacy of reducing the user workload compared to manual control. CONCLUSION: The EAST colonoscope can perform visual servoing and semi-autonomous manipulations with the developed methods in both laboratory and ex-vivo environments. SIGNIFICANCE: The proposed solutions and techniques improve the autonomy level of robotic colonoscopes and reduce user workloads, which promotes the development and clinical translation of robotic colonoscopy.

Rapamycin can alleviate the submandibular gland pathology of Sjögren's syndrome by limiting the activation of cGAS-STING signaling pathway.

BACKGROUND: Sjögren's Syndrome (SS) is also known as autoimmune exocrine gland disease. Previous studies have confirmed that adaptive immunity plays an important role in the development of this disease. But less is known about the role of the innate immune system. METHODS: To identify the core pathways, and local infiltrated immune cells in the local immune microenvironment of SS. We verified the activation of these core genes and core signaling pathways in SS model mice by in vivo experiment and transcriptome sequencing. RESULTS: Finally, we identified 6 core genes EPSTI1, IFI44L, MX1, CXCL10, IFIT3, and IFI44. All the 6 genes had good diagnostic value. Based on multi-omics sequencing results and experimental studies, we found that cGAS-STING signaling pathway is most relevant to the pathogenesis of SS. By in vivo experiments, we verified that autophagy is the key brake to limit the activation of cGAS-STING signaling pathway. CONCLUSIONS: Maladaptive activation of autophagy and cGAS-STING signaling pathway are central contributors to the SG pathogenesis of pSS patient. Regulating autophagy by rapamycin may be a possible treatment for Sjögren's syndrome in the future.

A Semi-Autonomous Stereotactic Brain Biopsy Robotic System With Enhanced Surgical Safety and Surgeon-Robot Collaboration.

OBJECTIVE: Despite benefits brought by recent neurosurgical robots, surgical safety and surgeon-robot collaboration remain significant challenges. In this article, we analyze and address these problems in the context of brain biopsy, by proposing a semi-autonomous system. METHODS: A robotic module is designed for the automation of all the brain biopsy procedures, and a biopsy cannula with tissue blocker is developed to avoid tissue excess and haemorrhage. In addition, two methods are proposed for surgical safety and surgeon-robot collaboration enhancement. First, a priority-based control framework is proposed for neuronavigation with simultaneous optical tracking line-of-sight maintenance and surgeon avoidance. Second, after neuronavigation, an adaptive reconfiguration method is developed to optimize the arm angle of KUKA robot based on the surgeon's pose, for workspace interference minimization, high robot dexterity, and joint-limit avoidance. RESULT: Effectiveness of the proposed solution demonstrated by simulations and experiments. CONCLUSION: The system can perform automatic navigation with simultaneous optical tracking maintenance and surgeon avoidance, autonomous brain biopsy, and adaptive reconfiguration for workspace interference minimization. SIGNIFICANCE: This work improves existing neurosurgical systems, in terms of autonomy level from mechanical guidance to task autonomy, surgical safety, and surgeon-robot collaboration.

Xinkeshu for coronary heart disease complicated with anxiety or depression: A meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of coronary heart disease (CHD) complicated with anxiety or depression is increasing year by year. However, many anti-anxiety drugs or antidepressants have a certain degree of adverse reactions and are not easily accepted by patients. Xinkeshu (XKS), as a proprietary Chinese patent medicine with "psycho-cardiology" effect, is one of the commonly used drugs in the treatment of CHD complicated with anxiety or depression in China. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of XKS for CHD complicated with anxiety or depression. METHODS: Nine different electronic databases were independently searched to include randomized controlled trials (RCTs) of XKS for CHD complicated with anxiety or depression published from inception to February 2022, and the methodological quality was evaluated using the bias risk assessment tool from Cochrane Handbook 5.0 and the modified Jadad scale. Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. The GRADE Profiler 3.6.1 and TSA 0.9.5.10 beta were adopted to evaluate the certainty and conclusiveness of the evidence. RESULTS: A total of 18 RCTs involving 1907 subjects were included. There were 956 subjects in the XKS group and 951 subjects in the control group. Baseline conditions were consistent and comparable between the groups. Compared with single-use western medicine (WM), XKS combined with WM significantly reduced scores of Hamilton Anxiety Scale (HAMA) [Mean difference (MD) = -7.60, 95% confidence interval (95% CI) (-10.37, -4.83), P < 0.000 01], Zung Self-rating Anxiety Scale (SAS) [MD = -10.05, 95% CI (-12.70, -7.41), P < 0.000 01], Hamilton Depression Scale (HAMD) [MD = -6.74, 95% CI (-11.58, -1.90), P = 0.006], and Zung Self-rating Depression Scale (SDS) [MD = -10.75, 95% CI (-17.05,-4.45), P = 0.000 8], as well as improved clinical effective rate [odds ratio (OR) = 4.24, 95% CI (2.47, 7.27), P < 0.000 01]. In terms of safety, 4 studies reported the adverse reactions in detail. The severity was mild and symptoms disappeared after treatment. CONCLUSION: Current evidence indicates that XKS may be effective and safe in the treatment of patients with CHD complicated with anxiety or depression. Since the quality of the literature included in this study was generally low, there is an urgent need for more RCTs with high quality, low bias risk and sufficient sample size to validate our conclusions.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Aidi Injection Treating of Nonsmall Cell Lung Cancer.

Background: Aidi injection (ADI) is a compound preparation injection of Chinese herbs used to treat patients of nonsmall cell lung cancer (NSCLC) in China. This study aimed to reveal the mechanism of ADI in the treatment of NSCLC by using network pharmacology and molecular docking. Methods: The related targets of ADI and NSCLC were obtained from multiple databases. The network diagram of disease-drug-components-targets (DDCT) and protein-protein interaction (PPI) was constructed to screen key targets. Then, the key targets and main signaling pathways were screened by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Next, in order to validate the results of network pharmacology, expression analysis and survival analysis of key genes were performed. Finally, we carried out the technology of molecular docking to further validate the accuracy of the above results. Results: A total of 207 targets of ADI and 5282 targets of NSCLC were obtained finally. Through the construction of DDCT and PPI network diagrams, 28 key targets were finally obtained. The results of the KEGG enrichment analysis indicated that multiple signaling pathways were associated with NSCLC, which included the MAPK signaling pathway, the IL-17 signaling pathway, and the PI3K/AKT signaling pathway. The key genes in the signaling pathway mainly include TP53, CASP3, MMP9, AKT1, PTGS2, and MAPK1. The results of differently expressed analysis of key genes showed that TP53, CASP3, MMP9, AKT1, PTGS2, and MAPK1 had statistical differences in lung squamous cell carcinoma (LUSC) compared with normal tissue (p < 0.001). In lung adenocarcinoma (LUAD), the expression of TP53, CASP3, MMP9, AKT1, and PTGS2 had statistical differences compared with normal tissue (p < 0.001), while the expression of MAPK1 had no statistical difference (p > 0.05). The results of survival analysis of key genes showed that AKT1, MAPK1, CASP3, MMP9, TP53, and PTGS2 had statistical differences in the OS or RFS of NSCLC patients (p < 0.05). In addition, the results of molecular docking indicated that the key genes and the main components have good docking activity. Conclusions: This study revealed the potential mechanism of ADI in the treatment of NSCLC with multipathways and multitargets and provided a scientific basis for the in-depth study of ADI in the treatment of NSCLC.

Connective tissue disease-related interstitial lung disease is alleviated by tripterine through inhibition of the PI3K/Akt, apoptosis, and TNF-α signalling pathways.

Background: Interstitial lung disease (ILD) is the major cause of morbidity and mortality in patients with various rheumatic diseases. However, more interventions need to be sought. Tripterine, an extract of Tripterygium wilfordii Hook. F, has been widely studied for its powerful anti-inflammatory effect. However, its mechanism of action in treating connective tissue disease-related (CTD)-ILD remains unclear. Purpose: To investigate the mechanism of tripterine in CTD-ILD treatment by combining network pharmacology and an in vivo experiment. Methods: The related targets of tripterine were obtained after searching the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform, Comparative Toxicogenomics Database, GeneCards, Search Tool for Interacting Chemicals database, and SymMap database. Following this, Online Mendelian Inheritance in Man, GeneCards, Genebank, and DrugBank were used to screen the targets of CTD-ILD. A target-signalling pathway network was constructed using Cytoscape. Additionally, topological analysis was performed. Protein interaction analysis was performed using the STRING online analysis platform. Following this, Gene Ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) signalling pathway enrichment analyses were performed. Subsequently, the molecular docking between tripterine and the core targets was verified. Finally, experimental verification was performed in bleomycin-induced model mice. Results: A total of 134 common targets and 10 core targets of tripterine, including signal transducer and activator of transcription 3, tumour necrosis factor (TNF), v-rel avian reticuloendotheliosis viral oncogene homolog A, protein kinase B (Akt) α (Akt1), mitogen-activated protein kinase (MAPK) 1, Jun transcription factor family, tumour protein 53, MAPK3, nuclear factor kappa B subunit 1, and caspase 8, were obtained. GO enrichment analysis revealed that, while treating CTD-ILD, tripterine was mainly involved in cytokine receptor binding, receptor-ligand activity, signal receptor activation, cytokine activity, protein ubiquitination, deoxyribonucleic acid transcriptase activity, etc. The KEGG pathway enrichment analysis revealed that the most significant signalling pathways were multiple viral infections and the phosphatidylinositol-3-kinase (PI3K)/Akt, TNF, and apoptosis signalling pathways. Molecular docking results revealed that tripterine had good docking activity with the core targets. Experimental studies also demonstrated that tripterine could inhibit the activation of PI3K/Akt, apoptosis, and TNF-α signalling pathways in lung tissue and significantly improve lung pathology and collagen deposition in the model mice. Conclusions: This study preliminarily revealed the potential molecular biological mechanism of tripterine while treating CTD-ILD might be related to inhibiting the PI3K/Akt, apoptosis, and TNF-α signalling pathways. Tripterygium wilfordii Hook. F. and its extract could be used clinically for treating CTD-ILD.

The mechanism of triptolide in the treatment of connective tissue disease-related interstitial lung disease based on network pharmacology and molecular docking.

BACKGROUND: Interstitial lung disease (ILD) is associated with substantial morbidity and mortality, which is one of the key systematic manifestations of connective tissue disease (CTD). Tripterygium wilfordii, known as Leigongteng in Chinese, has been applied to treat connective tissue disease-related interstitial lung disease (CTD-ILD) for many years. Triptolide is a key effective component from Tripterygium wilfordii. But the molecular mechanism of Triptolide for treating CTD-ILD is not yet clear. METHODS: Gaining insight into the molecular mechanism of Triptolide intervention CTD-ILD, we used the method of network pharmacology. And then we conducted drug-target networks to analyse the potential protein targets between Triptolide and CTD-ILD. Finally, AutoDock Vina was selected for molecular docking. RESULTS: By analysing the interaction genes between Triptolide and CTD-ILD, 242 genes were obtained. The top 10 targets of the highest enrichment scores were STAT3, AKT1, MAPK1, IL6, TP53, MAPK3, RELA, TNF, JUN, JAK2. GO and KEGG enrichment analysis exhibited that multiple signalling pathways were involved. PI3K-Akt, multiple virus infections, cancer signalling, chemokine, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. And it is related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. Molecular docking shows Triptolide can bind with its target protein in a good bond by intermolecular force. CONCLUSIONS: This study preliminarily reveals the internal molecular mechanism of Triptolide interfere with CTD-ILD through multiple targets, multiple access, validated through molecular docking.KEY MESSAGESTriptolide intervention CTD-ILD, which are related to various biological processes such as inflammation, infection, cell apoptosis, and cancer.PI3K-Akt, multiple virus infections, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD.Triptolide can bind with related target protein in a good bond by Intermolecular force, exhibiting a good docking activity.

Impact of fear of hypoglycaemia on self-management in patients with type 2 diabetes mellitus: structural equation modelling.

AIMS: This study aimed to explore the effect of fear of hypoglycaemia (FOH) on self-management and its specific action path in patients with type 2 diabetes mellitus (T2DM) to provide a basis for developing targeted nursing interventions. DESIGN: A cross-sectional study. METHODS: From June to October 2019, we recruited 258 patients with T2DM from the endocrinology department of three hospitals to complete questionnaires, including the Hypoglycaemia Fear Survey-II, Diabetes Distress Scale, Self-Stigma Scale, Social Support Rating Scale and Summary of Diabetes Self-Care Activities, in Jiangsu Province, China. Pearson's correlation analyses and structural equation modelling were conducted to explore the relationship and influence path among the above variables. RESULTS: The correlation analysis of FOH, distress, self-stigma, social support and self-management showed that, except for social support not being correlated with FOH and distress (P > 0.05), all variables were correlated in pairs (r = - 0.19-0.77, P < 0.01). The final model fit well, and the fitting indexes of the model were as follows: χ2/df = 2.191, GFI = 0.934, CFI = 0.954, TLI = 0.934, RMSEA = 0.068, and SRMR = 0.0649. The effects of FOH on self-management in patients with T2DM included one direct path and two indirect paths: (a) FOH had a direct impact on self-management (P < 0.05); (b) FOH had an indirect impact on self-management through distress (P < 0.05); and (c) FOH had an indirect impact on self-management through self-stigma and social support (P < 0.05). CONCLUSIONS: FOH could directly influence self-management in patients with T2DM. Furthermore, distress, self-stigma and social support were important mediating variables of FOH influencing self-management. Researchers can develop personalized interventions to improve the self-management of patients with T2DM by regulating distress, self-stigma and social support levels.

Efficacy and Safety of Tripterygium Wilfordii Hook. F for Connective Tissue Disease-Associated Interstitial Lung Disease:A Systematic Review and Meta-Analysis.

Background: Tripterygium wilfordii Hook. F (TwHF), a Chinese herbal medicine used to treat CTD-ILD patients in China, has been previously found to have immunoinhibitory, antifibrotic and anti inflammatory effects. It has also shown good results in treating autoimmune and inflammatory diseases. Objectives: This systematic review and meta-analysis aims to evaluate the efficacy and safety of TwHF for CTD-ILD. Methods: A systematic search was performed on PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, Scopus, CNKI, Wanfang, VIP, and CBM databases up to May 2021. Randomized controlled trials (RCTs) comparing TwHF plus conventional therapy versus conventional therapy alone were included. We followed the PRISMA checklist, and applied Cochrane handbook 5.1.0 and RevMan 5.3 for data analysis and quality evaluation of the included studies. Results: Based on Cochrane handbook 5.1.0, nine RCTs consisting 650 patients met the inclusion/exclusion criteria and were selected for further analysis. The obtained data showed significant improvement in lung function with TwHF plus conventional treatment compared with conventional treatment (post-treatment FVC% (MD= 8.68, 95%Cl (5.10, 12.26), p < 0.00001), FEV1% (MD = 11.24, 95%Cl (6.87, 15.61), p < 0.00001), TLC% (MD = 5.28, 95%Cl (0.69, 9.87), p = 0.02)], but no significant difference in the post-treatment DLCO% [(MD = 4.40, 95%Cl (-2.29, 11.09), p = 0.20)]. Moreover, the data showed that TwHF combined with conventional treatment significantly reduced the HRCT integral of patients [MD = -0.65, 95% (-1.01, -0.30), p = 0.0003], the level of erythrocyte sedimentation rate (MD = -9.52, 95%Cl (-11.55, -7.49), p < 0.00001), c-reactive protein (CRP) (MD = -8.42, 95%Cl (-12.47, -4.38), p < 0.0001), and rheumatoid factor (MD = -25.48, 95%Cl (-29.36, -21.60), p < 0.00001). Compared to conventional therapy, TwHF combined with conventional therapy significantly improved clinical effects (RR = 1.33, 95%Cl (1.17, 1.51), p < 0.0001), in five trials with 354 patients. In terms of improvement of symptoms and signs, the TwHF group showed a more significant improvement than the conventional treatment group (Cough (MD = -0.96, 95%Cl (-1.43, -0.50), p < 0.0001), velcro rales (MD = -0.32, 95%Cl (-0.44, -0.20), p < 0.00001), shortness of breath (MD = -1.11, 95%Cl (-1.67, -0.56), p < 0.0001)], but no statistical difference in dyspnea (MD = -0.66, 95%Cl (-1.35, 0.03), p = 0.06). There was no statistical significance in the incidence of adverse reactions. Conclusion: The performed meta-analysis indicated that TwHF combined with conventional treatment was more beneficial to patients for improving symptoms, lung function and laboratory indicators. As it included studies with relatively small sample size, the findings require confirmation by further rigorously well-designed RCTs.

Comparison between two anammox fiber fillers under load impact and the effect of HCO3 - concentration.

Based on the establishment of a stable anaerobic ammonia oxidation treatment system in 100 days, the impact resistances of two different anammox fiber fillers (the curtain filler: R1 and the bundle filler: BR) were compared. Furthermore, the effect of HCO3 - concentration on the bundle filler system was also investigated, the results have shown that the activity of the two anammox fiber fillers was not inhibited when the NO2 --N concentration was lower than 750 mg L-1 (FNA = 0.085 mg L-1), while it was significantly suppressed at 900 mg L-1 (FNA = 0.118 mg L-1). However, the two fiber fillers could be recovered and exhibit a good impact resistance reduction of the substrate concentration. On day 95, the structure of the bundle filler was more conducive to the stable attachment, proliferation, and aggregation of anammox bacteria. Dominant anammox bacteria in both the curtain and bundle fillers were Candidatus Kuenenia, which accounted for 25.9% and 35.9% of the total population, respectively. When the influent HCO3 - concentration was 900 mg L-1, the bundled fiber filler had the highest total nitrogen (TN) removal efficiency, which reached 89.0%. Even though it was inhibited under 2000 mg L-1 of HCO3 - concentration, the reactor was able to recover within one week by reducing the substrate concentration. In addition, the HCO3 - inhibition mechanism was independent of pH, which resulted in high FA content.

[Analysis of tobacco style features using near-infrared spectroscopy and projection model].

In the present paper, a total of 4,733 flue-cured tobacco samples collected from 2003 to 2012 in 17 provincial origins and 5 ecological areas were tested by near infrared spectroscopy, including the NONG(Luzhou) flavor 1,580 cartons, QING (Fen) flavor 2004 cartons and Intermediate flavor 1 149 cartons. Using projection model based on principal component and Fisher criterion (PPF), Projection analysis models of tobacco ecological regions and style characteristics were established. Reasonableness of style flavor division is illustrated by the model results of tobacco ecological areas. With the Euclidean distance between the predicted sample projection values and the mean projection values of each class in style characteristics model, a description is given for the prediction samples to quantify the extent of the style features, and their first and second close categories. Using the dispersion of projected values in model and the given threshold value, prediction results can be refined into typical NONG, NONG to Intermediate, Intermediate to NONG, typical Intermediate, Intermediate to QING, QING to Intermediate, typical QING, QING to NONG, NONG to QING, or super-model range. The model was validated by 35 tobacco samples obtained from the re-dryingprocess in 2012 with different origins and parts. This kind of analysis methods not only can achieve discriminant analysis, but also can get richer feature attribute information and provide guidance to raw tobacco processing and formulations.