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Background Inflammation and metabolic syndrome (MetS) may act synergistically and possibly accelerate the initiation and progression of colorectal cancer (CRC). We prospectively examined the joint effect of MetS and inflammation on the risk of CRC. Methods We studied 92,770 individuals from the Kailuan study. MetS was defined based on the presence of three or more of the following components. (1) high glucose: FPG > 5.6 mmol/L; (2) high blood pressure: SBP ≥ 130 mmHg or DBP ≥ 85 mmHg; (3) high triglycerides: triglycerides > 1.69 mmol/L; (4) low HDL-C: HDL-C Results Compared with metabolically healthy noninflammatory individuals, inflammatory participants without MetS and inflammatory participants with MetS were associated with a 1.3-fold and 4.18-fold increased risk of CRC with corresponding HRs (95% CI) of 1.34 (1.09, 1.64) and 4.18 (3.11, 5.62), respectively. The combination of MetS and inflammation was associated with the highest risk of CRC in all subgroups, especially among participants who were female, in younger age, and obese. Sensitivity analyses further validated our primary findings. Conclusions We found the combination of MetS and inflammation could significantly increase the risk of CRC. Including CRP in the diagnosis of MetS may help to identify additional high-risk participants who should be targeted for early diagnosis and prevention of CRC. Trial registration Kailuan study, ChiCTR–TNRC–11001489. Registered 24 August, 2011-Retrospectively registered, http:// www.chictr.org.cn/showprojen.aspx?proj=8050

To explore in myeloperoxidase-antineutrophil cytoplasmic autoantibody-associated vasculitis (MPO-AAV) the value of circulating oncomarkers in identifying interstitial lung disease (ILD) and predicting prognosis.Newly diagnosed MPO-AAV patients were evaluated retrospectively at a single center. The serum levels of carbohydrate antigen (CA) 19-9, CA125, cytokeratin fraction 21-1 (CYFRA21-1), carcinoembryonic antigen, squamous cell carcinoma antigen, and neuron-specific enolase were compared between patients with and without ILD. The strength of the oncomarkers in identifying ILD was assessed through logistic regression and receiver operating characteristic (ROC) curves. Correlation analysis was applied to detect the associations between oncomarkers and ILD severity. The significance of serum oncomarkers as prognosis predictors for MPO-AAV associated ILD was evaluated by survival analysis.169 MPO-AAV patients were included and ILD was found in 101 patients. Serum CA125, CA19-9, and CYFRA21-1 were significantly higher in patients with ILD than those without ILD. The area under the ROC curve of CA19-9, CA125, and CYFRA21-1 for identifying ILD was 0.701, 0.660, and 0.711, respectively. A specificity of 98.5% for diagnosing ILD was found for CA19-9 at the recommended normal level. CA19-9 was positively correlated with HRCT fibrosis score (r = 0.498, p 0.001) and CYFRA21-1 was correlated with ground-glass score (r = 0.316, p = 0.002). Both CA19-9 and CYFRA21-1 were independent risk factors for all-cause mortality in patients with ILD.Serum CA19-9 and CYFRA21-1 might be useful markers in the diagnosis, disease severity evaluation, and prognosis prediction of MPO-AAV-associated ILD.

Background ONC201 is a dopamine receptor D2 (DRD2) antagonist that inhibits tumor growth in preclinical models through ClpP activation to induce integrated stress response pathway and mitochondrial events related to inhibition of cell growth, which is being explored in clinical trials for solid tumors and hematological malignancies. In this study, we investigated the anti-tumorigenic effect of ONC201 in endometrial cancer cell lines and a genetically engineered mouse model of endometrial cancer. Methods Cell proliferation was assessed by MTT and colony formation assays. Cell cycle and apoptosis were evaluated by Cellometer. Invasion capacity was tested using adhesion, transwell and wound healing assays. LKB1fl/flp53fl/fl mouse model of endometrial cancer were fed a control low fat diet versus a high fat diet to mimic diet-induced obesity. Following tumor onset, mice were treated with placebo or ONC201. Metabolomics and lipidomics were used to identify the obesity-dependent effects of ONC201 in the mouse endometrial tumors. DRD2 expression was analyzed by immunohistochemistry in human endometrioid and serous carcinoma specimens. DRD2 mRNA expression from the Cancer Genome Atlas (TCGA) database was compared between the four molecular subtypes of endometrial cancer. Results Increasing DRD2 expression in endometrial cancer was significantly associated with grade, serous histology and stage, as well as worse progression free survival and overall survival. Higher expression of DRD2 mRNA was found for the Copy Number High (CNH) subtype when compared to the other subtypes. ONC201 inhibited cell proliferation, induced cell cycle G1 arrest, caused cellular stress and apoptosis and reduced invasion in endometrial cancer cells. Diet-induced obesity promoted endometrial tumor growth while ONC201 exhibited anti-tumorigenic efficacy in the obese and lean LKB1fl/fl/p53fl/fl mice. Metabolomic analysis demonstrated that ONC201 reversed the obesity-driven upregulation of lipid biosynthesis and reduced protein biosynthesis in obese and lean mice. Conclusion ONC201 has anti-tumorigenic effects in endometrial cancer cells and a transgenic mouse model of endometrial cancer, and DRD2 expression was documented in both human serous and endometrioid endometrial cancer. These studies support DRD2 antagonism via ONC201 as a promising therapeutic strategy for endometrial cancer that has already demonstrated pharmacodynamic activity and clinical benefit in both serous and endometrioid endometrial cancer patients.

Pregnant women are at high risk of developing subclinical hypothyroidism (SCH), and anti-thyroid peroxidase antibody (TPOAb) positivity can further inhibit thyroxine synthesis. Emerging evidence indicates that intestinal flora can modulate metabolic and immune homeostasis. The characteristics of intestinal flora of TPOAb-positive women with SCH in their second trimester of pregnancy have not been reported. This single-center prospective observational cohort study investigated gut microbial composition and metabolic function using sequencing of the 16S rRNA gene in fecal samples from 75 TPOAb-positive women with SCH and 90 TPOAb-negative women with SCH during their second trimester of pregnancy. Women were treated with no levothyroxine (LT4), low-dose LT4 (≤50ug/d), or high-dose LT4 (>50ug/d). Taxonomic analysis showed Firmicutes and Bacteroidetes were the dominant phyla, followed by Actinobacteria and Proteobacteria. Faecalibacterium, Bacteroides, Prevotella 9, Bifidobacterium, Subdoligranulum, Lachnospira, and Megamonas were the predominant genera. The intestinal flora of TPOAb-positive women with SCH who received no LT4 was characterized by bacterial amplicon sequence variants (ASVs)/operational taxonomic units (OTUs) enriched in the genus Subdoligranulum. The intestinal flora of TPOAb-positive women with SCH who received low-dose or high-dose LT4 were characterized by bacterial ASVs/OTUs depleted of the species Ruminococcus sp._or Bacteroides massiliensis, respectively. A total of 19 metabolic functions of intestinal flora, mainly involving lipid and amino acid metabolism, discriminated TPOAb-positive and TPOAb-negative women with SCH. Our study suggests that there are differences in the composition and metabolic function of intestinal flora of TPOAb-positive and TPOAb-negative women with SCH treated with different doses of LT4 in the second trimester of pregnancy. The findings provide insight into intestinal flora as novel targets for the treatment of TPOAb-positive women with SCH during pregnancy.

Background Although several histological studies have documented airway inflammation and remodelling in the small airways of dust-exposed workers, little is known regarding the prevalence and risk factors of small airway dysfunction (SAD) in pneumoconiosis. The present study investigated the prevalence and characteristics of spirometry-defined SAD in pneumoconiosis and assessed the risk factors for associated with SAD. Methods A total of 1255 patients with pneumoconiosis were invited to participate, of whom 1115 patients were eligible for final analysis. Spirometry was performed to assess SAD using the following three indicators: maximal mid-expiratory flow and forced expiratory flow 50% and 75%. SAD was defined as at least two of these three indicators being less than 65% of predicted value. Logistic regression analyses were used to analyse the relationships between clinical variables and SAD. Results Overall, 66.3% of patients with pneumoconiosis had SAD, among never-smokers the prevalence of SAD was 66.7%. The proportion of SAD did not differ among the subtypes of pneumoconiosis. In addition, SAD was present across the patients with all stages of pneumoconiosis. Even among those with forced expiratory volume in 1 s (FEV1) ≥ 80% and FEV1/forced vital capacity ratio ≥ 70%, 40.8% of patients had SAD. Patients with SAD were older than patients without SAD, more likely to be women and heavy smokers. Importantly, patients with SAD had more severe airflow obstruction, air trapping, and diffusion dysfunction. All patients with both pneumoconiosis and chronic obstructive pulmonary disease had SAD. Based on multivariate analysis, overall, aged 40 years and older, female sex, heavy smoking, body mass index ≥ 25.0 kg/m2 and pneumoconiosis stage III were significantly associated with increased risk of SAD. Among the never smokers, risk factors for SAD included female sex, BMI ≥ 25.0 kg/m2, pneumoconiosis stage II and stage III Conclusion Spirometry-defined SAD is one of the common functional abnormalities caused by occupational dust exposure and should be taken into account when monitoring respiratory health of workers to guide the early precautions and management in pneumoconiosis.

Premature infants have a fragile ecology of the gut microbiota, which is associated with many health problems and may be influenced by formula versus breast feeding. The present study investigated differences in the process of gut microbiota colonisation in preterm infants fed with breastmilk or formula with or without probiotics before 12 weeks. This cohort study recruited 138 premature infants, 31 in the breastmilk (BM) group, 59 in the probiotics formula (PF) group and 48 in the non-probiotics formula (NPF) group, according to the feeding practice they received at birth. Gut bacterial composition was identified with 16S rRNA gene sequencing in faecal samples collected at 1 week, 6 weeks and 12 weeks after birth. The alpha diversity was higher in the PF group compared to the other groups at week 1 and 6 (both p &lt, 0.01) but showed no difference at week 12. The beta diversity of the three groups showed a trend towards similarity at the first two stages (p &lt, 0.001 and p = 0.009, respectively) and finally showed no difference at week 12. Canonical redundancy analysis showed that feeding type could explain the difference in gut microbiota composition at week one and six (both p &lt, 0.01). At genus level, Bifidobacterium was enriched in the PF group, while the Enterococcus and Streptococcus was enriched in the NPF group. In summary, formula with probiotics feeding after birth can affect gut microbiota colonisation and lead to a bacterial community with less potential pathogens.

Objectives To explore the circulating metabolites and related pathways in silicosis and asbestosis exposure to different mineral dusts. Methods Plasma of 30 silicosis, 30 asbestosis, and 20 healthy controls was analyzed using liquid chromatography-mass spectrometry. Metabolic networks and the relevance of the identified metabolic derangements were explored. Results Compared with healthy controls, 37 and 39 dysregulated plasma metabolites were found in silicosis and asbestosis respectively, of which the levels of 22 metabolites differed. Three major pathways were identified, among which arginine and proline metabolism was identified as the most closely related metabolic pathway. Conclusions The types and quantities of up-regulated metabolites including lipids, amino acids, and carnitines were differed between silicosis and asbestosis. Pathways inducing lung fibrosis were common to mineral dusts exposure, while pathways related to oxidative stress and tumorigenesis differed between silicosis and asbestosis.

Background Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. This study aimed to identify different metabolic features in the plasma of patients with silicosis and dust-exposed workers without silicosis in metabolomics studies. Methods Patients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case–control study. The metabolomics analyses by ultra-high performance liquid chromatography-mass spectrometry were conducted. Distinct metabolic features (DMFs) were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored. Results Twenty-nine DMFs and 9 DMFs were detected and had the same trend in the pilot study and the validation study in the plasma of the DEW and silicosis groups, respectively. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. l-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis. Conclusions Distinct metabolic features in the plasma of DEWs and the patients with silicosis were found to be different. Sphingolipid metabolism and arginine and proline metabolism were identified as the major metabolic pathway in the DEW and silicosis groups, respectively. l-arginine and kynurenine were correlated with the severity of silicosis.

ObjectivesOccupational dust exposure may induce various lung diseases, including pneumoconiosis and chronic obstructive pulmonary disease (COPD). The features of combined COPD and pneumoconiosis have not been well described, and this may hamper the management. This study aimed to describe the prevalence and characteristics as well as the risk factors of the combined diseases.DesignA cross-sectional study.Setting and participants758 patients with pneumoconiosis were recruited at a single-medical centre. Of these, 675 patients with pneumoconiosis, including asbestosis, silicosis, coal workers’ pneumoconiosis and other pneumoconiosis, was eligible for analysis.Primary outcome measuresCOPD was diagnosed based on clinical features and/or history of exposure to risk factors and post bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio ResultsCOPD prevalence overall was 32.7% (221/675) and was the highest in silicosis (84/221) and coal workers’ pneumoconiosis (100/221). COPD prevalence increased with smoking pack-years, dust exposure duration and pneumoconiosis stage. Patients with combined diseases had lower body mass index, higher smoking index and worse pulmonary function. Risk factors for combined diseases included heavy smoking, silica or coal exposure and advanced pneumoconiosis. The interaction between dust exposure and smoking in COPD was also identified. The risk of combined COPD significantly increased with heavy smoking and silica or coal exposure (OR 5.49, 95% CI 3.04 to 9.93, pConclusionsCOPD is highly prevalent in patients with pneumoconiosis, especially patients with silicosis and coal workers’ pneumoconiosis. Occupational dust exposure as well as heavy smoking is associated with an increased risk of combined COPD and pneumoconiosis, which demands an effective preventive intervention.

There was limited evidence regarding the association between short-term exposure to ambient particulate matter (PM) and respiratory outpatient visits among children at a multicity level. In this study, a time-series study was conducted among children aged 0–14 years in five Chinese cities from 2013 to 2018. City-specific effects of fine particles (PM2.5), inhalable particles (PM10) and coarse particles (PM10-2.5) were estimated for time lags of zero up to seven previous days using the overdispersed generalized additive models after adjusting for time trends, meteorological variables, day of the week and holidays. Meta-analyses were applied to pool the overall effects, while the exposure-response (E-R) curves were evaluated using a cubic regression spline. The overall effects of PM were significantly associated with total and cause-specific respiratory outpatients among children, even at PM2.5 and PM10 levels below the current Chinese Ambient Air Quality Standards (CAAQS) Grade II. Each 10 μg/m3 increment in PM2.5, PM10 and PM10-2.5 at lag 07 was associated with a 1.39% (95% CI: 0.38%, 2.40%), 1.10% (95% CI: 0.38%, 1.83%) and 2.93% (95% CI: 1.05%, 4.84%) increase in total respiratory outpatients, respectively. An E-R relationship was observed except for PM2.5 in Beijing and PM10 and PM10-2.5 in Shanghai. The effects of PM were stronger in cold season in 3 southern cities, while it was stronger in transition season in 2 northern cities. In conclusion, short-term PM exposures were dose-responsive associated with increased respiratory outpatient visits among children, even for PM2.5 and PM10 levels below current CAAQS II in certain cities.

Background The traditional rehabilitation for neurological diseases lacks the active participation of patients, its process is monotonous and tedious, and the effects need to be improved. Therefore, a new type of rehabilitation technology with more active participation combining brain–computer interface (BCI) with virtual reality (VR) has developed rapidly in recent years and has been used in rehabilitation in neurological diseases. Objectives This narrative review analyzed and characterized the development and application of the new training system (BCI-VR) in rehabilitation of neurological diseases from the perspective of the BCI paradigm, to provide a pathway for future research in this field. Methods The review involved a search of the Web of Science-Science Citation Index/Social Sciences Citation Index and the China National Knowledge Infrastructure databases; 39 papers were selected. Advantages and challenges of BCI-VR – based neurological rehabilitation were analyzed in detail. Results Most BCI-VR studies included could be classified by 3 major BCI paradigms: motor imagery, P300, and steady-state visual-evoked potential. Integrating VR scenes into BCI systems could effectively promote the recovery process from nervous system injuries as compared with traditional methods. Conclusion As compared with rehabilitation based on traditional BCI, rehabilitation based on BCI-VR can provide better feedback information for patients and promote the recovery of brain function. By solving the challenges and continual development, the BCI-VR system can be broadly applied to the clinical treatment of various neurological diseases.

Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan–Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment.

To observe the clinical efficacy differences between acupuncture combined with 40-min penetration moxibustion and 60-min penetration moxibustion at back-Sixty patients of insomnia with insufficiency of heart and spleen type were randomly assigned into a 40-min group and a 60-min group. The two groups were treated with acupuncture at Jueyinshu (BL 14), Xinshu (BL 15), Geshu (BL 17), Pishu (BL 20), Shendao (GV 11) and Zhiyang (GV 9). With moxibustion box, the penetration moxibustion was applied at the back until sweating and redness on the back. The moxibustion was given for 40 min in the 40-min group and 60 min in the 60-min group. The treatment was given once a day, five days per week. Each session was consisted of 5 treatments, with an interval of 2 days between session and totally 4 consecutive weeks were provided. The Pittsburgh sleep quality index (PSQI), TCM symptom scale were observed and recorded before and after treatment in the two groups. The even temperature at raising period, effective period, reducing period, as well as minimum high temperature, comfortable temperature, minimum cold temperature and medication status were compared; also the effect was compared between the two groups.The total effective rate was 96.6% (28/29) in the 60-min group, which was higher than 89.3% (25/28) in the 40-min group (Acupuncture combined with penetration moxibustion can improve the symptomsof insomnia with insufficiency of heart and spleen type, which is more significant in the 60-min group, indicating prolonged time of penetration moxibustion can improve sleep latency.