The GGCT and REST positive feedback loop promotes tumor growth in Glioma.

BACKGROUND: γ-Glutamylcyclotransferase (GGCT), an enzyme crucial in glutathione metabolism, has emerged as a participant in tumorigenesis. The present study is designed to elucidate the biological role and molecular mechanisms underlying GGCT in glioma. METHODS: Gene Expression Profiling Interactive Analysis (GEPIA), Chinese Glioma Genome Atlas (CGGA), and PrognoScan online databases were utilized to examine the expressions and clinical prognosis of GGCT and REST in glioma. Cell Counting Kit-8 (CCK-8), Transwell, Wound healing, and Flow cytometric assays, and RNA-sequencing analysis were employed to uncover the molecular role of GGCT and REST. Prediction of Differentially expressed microRNA (DE-miRNAs) and miRNAs targeting GGCT 3' Untranslated Region (UTR) was performed using miRanda online datasets. Finally, Real time-quantitative Polymerase Chain Reaction (RT-qPCR), western blot and dual luciferase reporter gene activity analysis were employed to confirm a positive feedback loop involving GGCT/REST/miR-34a-5p in glioma cells. RESULTS: High expression of GGCT was correlated with poor prognosis in glioma. GGCT silencing demonstrated inhibitory effects on the proliferation, migration, and induction of apoptosis in T98G and U251 cells. Mechanistically, GGCT downregulated REST expression and modulated cancer-associated pathways in glioma cells. High expression of REST was associated with poor prognosis in glioma. In vitro and in vivo experiments showed that REST overexpression restored the repression of proliferation, invasion, migration, and xenograft tumor formation induced by GGCT knockdown. Furthermore, the study uncovered that REST inhibited miR-34a-5p mRNA expression, and miR-34a-5p suppressed GGCT expression by targeting its 3'UTR, forming a positive regulatory loop in glioma. Notably, the inhibitor of miR-34a-5p restored the role of REST silencing in decreasing GGCT expression in glioma cells. CONCLUSIONS: GGCT/REST/miR-34a-5p axis holds promising potential as a therapeutic target, offering a potential breakthrough in the treatment of glioma.

Qualitative study on the problems and potential solution strategies for part-time clinical pharmacists' clinical services work in a tertiary hospital in China.

OBJECTIVE: To provide an initial understanding of problems and potential solution strategies for part-time clinical pharmacist work in China, and provide references for the training of part-time clinical pharmacists. METHODS: The study was conducted in a tertiary teaching hospital in China, and the project lasted 6 months. Phenomenological methods were used to guide the research design. Research data were obtained by conducting one-to-one semistructured interviews with part-time clinical pharmacists, and interview data were coded and analysed through thematic analysis. RESULTS: A total of 21 pharmacists were interviewed in a semistructured manner, and the results showed that following problems exist in the work of part-time clinical pharmacists: the existing professional knowledge is not adequate to meet the demands of clinical service; the career orientation of part-time clinical pharmacists is not clear; lack of professional self-confidence in clinical pharmacy practice; there is no suitable entry point to carry out pharmacy service work; it is difficult to communicate effectively, and for in addition, 17 potential solution strategies are proposed for the current problems, which can provide reference for the development of part-time clinical pharmacists' work. CONCLUSIONS: The work performed by part-time clinical pharmacists is currently immature and the strategies derived from this study may serve as potential solutions to resolve the part-time clinical pharmacy practice challenges.

The neuroimmune pathway of high-altitude adaptation: influence of erythrocytes on attention networks through inflammation and the autonomic nervous system.

Introduction: Many studies have shown that the functional adaptation of immigrants to high-altitude is closely related to oxygen transport, inflammatory response and autonomic nervous system. However, it remains unclear how human attention changes in response to hypoxia-induced neurophysiological activity during high-altitude exposure. Methods: In the present study, we analyzed the relationship between hypoxic-induced neurophysiological responses and attention networks in 116 immigrants (3,680 m) using an attention network test to simultaneously record electroencephalogram and electrocardiogram in combination with specific routine blood markers. Results: Our analysis revealed that red blood cells exert an indirect influence on the three attention networks, mediated through inflammatory processes and heart rate variability. Discussion: The present study provides experimental evidence for the role of a neuroimmune pathway in determining human attention performance at high- altitude. Our findings have implications for understanding the complex interactions between physiological and neurocognitive processes in immigrants adapting to hypoxic environments.

Mapping the intellectual structure and landscape of colorectal cancer immunotherapy: A bibliometric analysis.

Immunotherapy, particularly immune checkpoint inhibitor (ICIs) therapy, stands as an innovative therapeutic approach currently garnering substantial attention in cancer treatment. It has become a focal point of numerous studies, showcasing significant potential in treating malignancies, including lung cancer and melanoma. The objective of this research is to analyze publications regarding immunotherapy for colorectal cancer (CRC), investigating their attributes and identifying the current areas of interest and cutting-edge advancements. We took into account the publications from 2002 to 2022 included in the Web of Science Core Collection. Bibliometric analysis and visualization were conducted using CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel. The quantity of publications associated with this domain has been steadily rising over the years, encompassing 3753 articles and 1498 reviews originating from 573 countries and regions, involving 19,166 institutions, 1011 journals, and 32,301 authors. In this field, China, the United States, and Italy are the main countries that come forward for publishing. The journal with the greatest impact factor is CA-A Cancer Journal for Clinicians. Romain Cohen leads in the number of publications, while Le Dt stands out as the most influential author. The immune microenvironment and immune infiltration are emerging as key hotspots and future research directions in this domain. This research carries out an extensive bibliometric examination of immunotherapy for colorectal cancer, aiding researchers in understanding current focal points, investigating possible avenues for research, and recognizing forthcoming development trends.

Jianpi Jiedu decoction reverses 5-fluorouracil resistance in colorectal cancer by suppressing the xCT/GSH/GPX4 axis to induce ferroptosis.

Introduction: Innate and acquired chemoresistance in colorectal cancer (CRC) often results in 5-fluorouracil (5-FU) treatment failure. This study aimed to investigate the potential of Jianpi Jiedu (JPJD) decoction to reverse 5-FU resistance in CRC and clarify its potential mechanism of action. Methods: The CCK-8 assay was employed to assess cell activity. Flow cytometry was employed to assess various parameters including cell apoptosis, cell cycle distribution, P-glycoprotein (P-gp) activity, reactive oxygen species levels, and lipid peroxidation. Metabolomics analysis was conducted to identify differentially expressed metabolites. Western blotting was utilized for protein expression analysis. Results: In this study, we demonstrated that the combined JPJD and 5-FU treatment reversed 5-FU resistance in HCT8/5-FU cells, inducing cell apoptosis, causing G2/M-phase cell cycle arrest, and reducing P-gp protein expression and activity. Metabolomics analysis revealed ferroptosis as a key pathway in the development of 5-FU resistance. Furthermore, the combination treatment reversed drug resistance primarily by impacting ferroptosis and triggering critical ferroptosis events through the suppression of the cystine/glutamate transporter (xCT)/glutathione (GSH)/glutathione peroxidase (GPX4) axis. Conclusion: JPJD decoction primarily suppressed the xCT/GSH/GPX4 axis to trigger ferroptosis, thereby effectively reversing 5-FU resistance in colorectal cancer (CRC).

Withanolides from Physalis angulata var. villosa and the Relative Configurational Revision of Some Known Analogs.

Physalis angulata var. villosa is a plant possessing abundant withanolides, but in-depth research is lacking. In our ongoing study of P. angulata var. villosa, 15 previously undescribed withanolides (1-15), along with 21 known analogs (16-36), were isolated from the whole plant. The structures of the withanolides (1-15) were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and ECD data. Additionally, the application of γ-gauche effects with the help of ROESY correlations led to the formulation of empirical rules for withanolides with 14-OH/15-OAc to rapidly determine the 14-OH orientations, making it possible to propose configurational revisions of 19 previously reported analogs (1'-19'). Withanolides 1, 4-6, and 10 showed potent cytotoxic activities against three human cancer cell lines (HCT-116, MDA-MB-231, and A549).

Association between the acceleration of access to visual awareness of grating orientation with higher heart rate at high-altitude.

Many studies have indicated a strong relationship between cardiac and brain activities, both of which are sensitive to high-altitude exposure. This study combined a consciousness access task and electrocardiograms (ECG) to uncover conscious awareness in response to high-altitude exposure and its relation to cardiac activity. When compared with the low-altitude groups, the behavioral results showed that the high-altitude participants shortened the time of access to visual awareness of grating orientation, which was accompanied by a faster heart rate, excluding the influence of pre-stimulus heart rate, extent of cardiac deceleration after presenting the stimulus, and task difficulty. Although there were post-stimulation cardiac deceleration and post-response acceleration at both high and low altitudes, a slight increase in heart rate after stimulation at high altitudes may indicate that participants at high altitudes could quickly readjust their attention to the target stimulus. More importantly, the drift diffusion model (DDM) was used to fit the access time distribution of all participants. These results suggest that shorter time at high altitudes might be due to the lower threshold, suggesting that less evidence in high-altitude participants was required to access visual consciousness. The participants' heart rates also negatively predicted the threshold through a hierarchical drift diffusion modeling (HDDM) regression. These findings imply that individuals with higher heart rates at high altitudes have a greater cognitive burden.

Neurodynamics of Awareness Detection in Tibetan Immigrants: Evidence from Electroencephalography Analysis.

The psychological effects of long-term exposure to high-altitude environments have attracted great attention. These effects are usually attributed to the diminished cognitive resources due to high-altitude exposure. This study employed electroencephalography (EEG) to investigate the effects of exposure duration on awareness detection tasks. Neither reaction time nor accuracy showed the direct effects of the exposure duration, so did the model indexes obtained from drift diffusion model analysis. However, event-related potentials (ERP) analysis revealed that exposure duration was associated with changes in the visual awareness negativity (VAN) and the late positivity (LP) components, which in turn affected reaction time. Specifically, longer exposure durations were associated with lower VAN and higher LP, resulting in shorter reaction times and greater drift rate. In contrast to previous studies, the reverse relationship between VAN and LP may reflect a compensatory response to the reduced cognitive resources caused by high-altitude exposure. Additionally, increased LP and shorter reaction times with exposure duration may reflect a resistance to the high-altitude environment. We also conducted time-frequency analysis and found that theta power did not vary with exposure duration, suggesting that the reduction in cognitive resources remains stable in these individuals over time. Overall, our study provides new insights into the dynamic effects of high-altitude environments on awareness detection in the presence of reduced cognitive resources.

New N-oxide alkaloids from the stems of Sinomenium acutum.

Six new alkaloids (1-6) and six known alkaloids (7-12) were obtained from the stems of Sinomenium acutum. Among them, compounds 1-3 and 6 were four N-oxide alkaloids. The structures and absolute configurations of these new alkaloids were elucidated through comprehensive data of 1D and 2D NMR, HRESIMS and ECD spectra. All isolated compounds were evaluated in vitro for their inhibitory activities against nitric oxide (NO) production and inhibitory effects on AChE. Among them, the sinomenine N-oxide (9) was the most potent NO production inhibitor, with an IC50 value of 23.04 µM.

Root-Associated Microbiomes of Panax notoginseng under the Combined Effect of Plant Development and Alpinia officinarum Hance Essential Oil.

Essential oils (EOs) have been proposed as an alternative to conventional pesticides to inhibit fungal pathogens. However, the application of EOs is considerably limited due to their highly volatile nature and unpredictable effects on other microbes. In our study, the composition of bacterial and fungal communities from the rhizosphere soil of P. notoginseng under four treatment levels of Alpinia officinarum Hance EO was characterized over several growth stages. Leaf weight varied dramatically among the four EO treatment levels after four months of growth, and the disease index at a low concentration (0.14 mg/g) of EO addition was the lowest among the P. notoginseng growth stages. The content of monomeric saponins was elevated when EO was added. Bacterial and fungal diversity in the absence of plants showed a decreasing trend with increasing levels of EO. Bacterial diversity recovery was more correlated with plant growth than was fungal diversity recovery. Compared with the control (no EO addition), a low concentration of EO significantly accumulated Actinomycota, including Acidothermus, Blastococcus, Catenulispora, Conexibacter, Rhodococcus, and Sinomonas, after one month of plant-microbial interaction. Overall, the results showed that both the plant growth stage and EOs drive changes in the microbial community composition in the rhizosphere of P. notoginseng. Plant development status had a stronger influence on bacterial diversity than on fungal diversity. EO had a more significant effect on fungal community composition, increasing the dominance of Ascomycota when EO concentration was increased. Under the interaction of P. notoginseng growth and EO, a large number of bacterial genera that have been described as plant growth-promoting rhizobacteria (PGPR) responded positively to low concentrations of EO application, suggesting that EO may recruit beneficial microbes in the root zone to cope with pathogens and reduce root rot disease. These results offer novel insights into the relationship between EO application, altered microbial communities in the plant roots, plant growth stage, and disease occurrence.

Bacillus-Secreted Oxalic Acid Induces Tomato Resistance Against Gray Mold Disease Caused by Botrytis cinerea by Activating the JA/ET Pathway.

Bacillus spp. are known for their ability to control plant diseases; however, the mechanism of disease control by Bacillus spp. is still unclear. Previously, bacterial organic acids have been implicated in the process of disease suppression. We extracted the total organic acid from Bacillus cereus AR156 culture filtrate and identified oxalic acid (OA) as the programmed cell death-inducing factor. OA strongly suppressed the lesion caused by Botrytis cinerea without significant antagonism against the fungus. Low concentration of OA produced by Bacillus spp. inhibited cell death caused by high concentrations of OA in a concentration- and time-dependent manner. Pretreatment with a low concentration of OA led to higher accumulation of active oxygen-scavenging enzymes in tomato leaves and provoked the expression of defense-related genes. The activation of gene expression relied on the jasmonic acid (JA) signaling pathway but not the salicylic acid (SA) pathway. The disease suppression capacity of OA was confirmed on wild-type tomato and its SA accumulation-deficient line, while the control effect was diminished in JA synthesis-deficient mutant, suggesting that the OA-triggered resistance relied on JA and ethylene (ET) signaling transduction. OA secretion ability was widely distributed among the tested Bacillus strains and the final environmental OA concentration was under strict regulation by a pH-sensitive degradation mechanism. This study provides the first systematic analysis on the role of low-concentration OA secreted and maintained by Bacillus spp. in suppression of gray mold disease and determines the dependence of OA-mediated resistance on the JA/ET signaling pathway. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention / 神经科学通报·英文版

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention.

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Mechanism of Anti-tuberculosis Particles （Kanglao Granule） Based on Network Pharmacology and Experimental Research / 中国实验方剂学杂志

ObjectiveTo explore the potential anti-tuberculosis mechanism of Kanglao granule through network pharmacology. MethodThe active components of Kanglao granule were retrieved from related databases and the potential targets of the components from SwissTargetPrediction. Targets of the tuberculosis were screened from GeneCards and National Center for Biotechnology Information （NCBI）， and the anti-tuberculosis targets of the prescription were further identified. STRING and Cytoscape 3.8.0 were employed to construct the Chinese medicinal-disease target-signaling pathway network and screen core targets. Then gene ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed. Finally， AutoDock Vina was used for molecular docking between the active components of the prescription and key proteins and Western blotting for verifying the interaction between them. ResultA total of 29 important chemical components in the prescription were screened out， including β-sitosterol， sesamin， and kaempferol. A total of 28 key anti-tuberculosis targets were retrieved， such as protein kinase B1 （Akt1）， epidermal growth factor receptor （EGFR）， hypoxia inducible factor-1A （HIF-1A）， proto-oncogene tyrosine-protein kinase （SRC）， and matrix metalloproteinase-9 （MMP-9）. Bioinformatics analysis showed the 28 targets were involved in 41 GO terms such as oxygen metabolism， nucleic acid transcription， and metabolic enzyme pathway， and 28 key KEGG pathways， including Mycobacterium tuberculosis signaling pathway and phosphatidylinositol 3 kinase/protein kinase B pathway. Molecular docking results showed that Akt1 had the strongest binding affinity to sesamin. In vitro experiment indicated that sesamin inhibited the growth of M. tuberculosis by suppressing the phosphorylation of Akt1. ConclusionKanglao granule improved the sterilization level and immune response through multi-component， multi-target， and multi-pathway interactions， thereby achieving therapeutic effect on tuberculosis. Akt1 is one of the important targets involved in the treatment of tuberculosis.

Electroencephalogram-Based Motor Imagery Classification Using Deep Residual Convolutional Networks.

The classification of electroencephalogram (EEG) signals is of significant importance in brain-computer interface (BCI) systems. Aiming to achieve intelligent classification of motor imagery EEG types with high accuracy, a classification methodology using the wavelet packet decomposition (WPD) and the proposed deep residual convolutional networks (DRes-CNN) is proposed. Firstly, EEG waveforms are segmented into sub-signals. Then the EEG signal features are obtained through the WPD algorithm, and some selected wavelet coefficients are retained and reconstructed into EEG signals in their respective frequency bands. Subsequently, the reconstructed EEG signals were utilized as input of the proposed deep residual convolutional networks to classify EEG signals. Finally, EEG types of motor imagination are classified by the DRes-CNN classifier intelligently. The datasets from BCI Competition were used to test the performance of the proposed deep learning classifier. Classification experiments show that the average recognition accuracy of this method reaches 98.76%. The proposed method can be further applied to the BCI system of motor imagination control.

Increased risk of cerebrovascular mortality in head and neck cancer survivors aged ≥ 65 years treated with definitive radiotherapy: a population-based cohort study.

BACKGROUND: To investigate the relationship between radiotherapy (RT) and the risk of cerebrovascular mortality (CVM) in head and neck cancer (HNC) survivors aged ≥ 65 years. METHODS: Patients with HNC survivors aged ≥ 65 years diagnosed between 2000 and 2012 were included from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis, Log-rank tests, and Cox proportional-hazards regression models were performed for statistical analyses. RESULTS: We included 16,923 patients in this study. Of these patients, 7110 (42.0%) patients received surgery alone, 5041 (29.8%) patients underwent RT alone, and 4772 (28.2%) patients were treated with surgery and RT. With a median follow-up time of 87 months, 1005 patients died with cerebrovascular disease. The 10-years CVM were 13.3%, 10.8%, and 11.2% in those treated with RT alone, surgery alone, and surgery plus RT, respectively (P < 0.001). The mean time for CVM was shorter in RT alone compared to surgery alone and surgery plus RT (52 months vs. 56-60 months). After adjusting for covariates, patients receiving RT alone had a significantly higher risk of developing CVM compared to those receiving surgery alone (hazard ratio [HR] 1.703, 95% confidence interval [CI] 1.398-2.075, P < 0.001), while a comparable risk of CVM was found between those treated with surgery alone and surgery plus RT (HR 1.106, 95% CI 0.923-1.325, P = 0.274). Similar trends were found after stratification age at diagnosis, gender, tumor location, and marital status. CONCLUSIONS: Definitive RT but not postoperative RT can increase the risk of CVM among older HNC survivors. Long-term follow-up and regular screening for CVD are required for HNC patients who received definitive RT to decrease the risk of CVM.

Contribution of mulch film to microplastics in agricultural soil and surface water in China.

Agricultural mulch film (AMF) is deemed an important source of microplastics (MPs) in agricultural soil (AS). However, quantitating the contribution of AMFs to MPs in farmland soil and surface water remains a considerable challenge to date. In the present study, a basic framework was developed to address these concerns. First, the concentrations of MPs in soil derived from AMF abrasion (CMP) and the total MPs from all sources in AS (CTMP) were measured. Then, the ratios of CMP to CTMP, i.e., the contribution of AMFs to MPs in AS, were calculated. The contribution of AMFs to MPs in surface water via soil erosion was calculated based on CTMP values, the ratios of CMP to CTMP, soil erosion intensities (SEIs), and farmland areas. Furthermore, the potential contribution of soil erosion to MPs in the ocean was estimated. In China, the inventory of MPs in surface AS in 2018 ranged from 4.9 × 106 to 1.0 × 107 tons according to our results. AMFs contributed 10%-30% of the CTMP with certainties of 60-95%. Assuming that all MPs in AS can be exhaustively transferred to surface water via soil erosion, the national mass transfer amount of MPs (MTTMP) from AS to surface water reached 1.2 × 105-2.2 × 105 tons (∼2% of the inventory of MPs in the AS of China); the fluxes of MPs into the ocean from AS were 3.4 × 104-6.6 × 104 tons, assuming that all MPs in the AS of coastal provinces enter the ocean. It is likely that AMFs contributed 10%-30% MTTMP and fluxes of MPs to the ocean according to the ratios of CMP to CTMP. Apparently, approximately 30% of the national MTTMP (i.e., the rate of MP flux to the ocean to MTTMP) was input to the ocean.

Evaluating the effects of cardiometabolic exposures on circulating proteins which may contribute to SARS-CoV-2 severity

Background: Developing insight into the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to overcome the global pandemic caused by coronavirus disease 2019 (covid-19). In this study, we have applied Mendelian randomization (MR) to systematically evaluate the effect of 10 cardiometabolic risk factors and genetic liability to lifetime smoking on 97 circulating host proteins postulated to either interact or contribute to the maladaptive host response of SARS-CoV-2. Methods: We applied the inverse variance weighted (IVW) approach and several robust MR methods in a two-sample setting to systemically estimate the genetically predicted effect of each risk factor in turn on levels of each circulating protein. Multivariable MR was conducted to simultaneously evaluate the effects of multiple risk factors on the same protein. We also applied MR using cis-regulatory variants at the genomic location responsible for encoding these proteins to estimate whether their circulating levels may influence SARS-CoV-2 severity. Findings: In total, we identified evidence supporting 105 effects between risk factors and circulating proteins which were robust to multiple testing corrections and sensitivity analyses. For example, body mass index provided evidence of an effect on 23 circulating proteins with a variety of functions, such as inflammatory markers c-reactive protein (IVW Beta=0.34 per standard deviation change, 95% CI=0.26 to 0.41, P=2.19x10-16) and interleukin-1 receptor antagonist (IVW Beta=0.23, 95% CI=0.17 to 0.30, P=9.04x10-12). Further analyses using multivariable MR provided evidence that the effect of BMI on lowering immunoglobulin G, an antibody class involved in protecting the body from infection, is substantially mediated by raised triglycerides levels (IVW Beta=-0.18, 95% CI=-0.25 to -0.12, P=2.32x10-08, proportion mediated=44.1%). The strongest evidence that any of the circulating proteins highlighted by our initial analysis influence SARS-CoV-2 severity was identified for soluble glycoprotein 130 (odds ratio=1.81, 95% CI=1.25 to 2.62, P=0.002), a signal transductor for interleukin-6 type cytokines which are involved in the bodys inflammatory response. However, based on current case samples for severe SARS-CoV-2 we were unable to replicate findings in independent samples. Interpretation: Our findings highlight several key proteins which are influenced by established exposures for disease. Future research to determine whether these circulating proteins mediate environmental effects onto risk of SARS-CoV-2 are warranted to help elucidate therapeutic strategies for covid-19 disease severity.

Erratum: A Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of LiuWei DiHuang Pill in Treating Type 2 Diabetes Mellitus [Corrigendum].

[This corrects the article DOI: 10.2147/DDDT.S216644.].

[Intestinal dysfunction of spinal cord injury treated with tongdu tiaoshen moxibustion: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect on intestinal dysfunction of spinal cord injury (SCI) between the comprehensive therapy of tongdu tiaoshen moxibustion (moxibustion for opening the governor vessel and regulating the spirit) and rehabilitation training and the simple treatment with rehabilitation training. METHODS: A total of 60 patients with intestinal dysfunction of SCI were randomized into a comprehensive therapy group and a rehabilitation group, 30 cases in each one (3 cases were dropped out in each group). On the base of the routine western medicine treatment and rehabilitation training, the bowel training and rectal function training were provided, once a day in the rehabilitation group. In the comprehensive therapy group, on the base of the treatment as the rehabilitation group, the tongdu tiaoshen moxibustion was exerted at Yaoyangguan (GV 3), Mingmen (GV 4), Zhiyang (GV 9), Dazhui (GV 14) and Baihui (GV 20), etc, once a day, 30 min each time. In both groups, the treatment for 4 weeks was as one course and 3 courses of treatment were required. Separately, before treatment, after 4, 8 and 12 weeks of treatment, the scores of neurogenic bowel dysfunction (NBD) and World Health Organization quality of life scale (WHOQOL-BREF) were observed and the clinical effect was evaluated after 12 weeks of treatment. RESULTS: After treatment, the total effective rate was 88.9% (24/27) in the comprehensive therapy group, which was higher than 74.1% (20/27) in the rehabilitation group (P<0.05). After 4, 8 and 12 weeks of treatment, NBD scores were all reduced obviously as compared with those before treatment in the two groups (all P<0.01). After 8 and 12 weeks of treatment, NBD scores in the comprehensive therapy group were lower than the rehabilitation group (both P<0.05). After 4, 8 and 12 weeks of treatment, the scores of all of the domains (psychology, physiology, social relations and environment) in WHOQOL-BREF were higher than those before treatment in the two groups (all P<0.01). After 4 weeks of treatment, the scores in the psychology and physiology domains in the comprehensive therapy group were higher than the rehabilitation group (all P<0.05). After 8 and 12 weeks of treatment, the scores of all of the domains in the comprehensive therapy group were higher than the rehabilitation group (all P<0.05). CONCLUSION: The comprehensive treatment of tongdu tiaoshen moxibustion and rehabilitation training achieves the better effect on intestinal dysfunction of SCI than the simple rehabilitation training and greatly improves the quality of life in SCI patients.