Insulin alleviates murine colitis through microbiome alterations and bile acid metabolism.

BACKGROUND: Insulin has been reported to exhibit anti-inflammatory activities in the context of bowel inflammation. However, the role of the interaction between insulin and the microbiota in gut health is unclear. Our goal was to investigate the mechanism of action of insulin in bowel inflammation and the relationship between insulin and the gut microbiota. METHODS: We used acute and chronic murine models of inflammatory bowel disease (IBD) to evaluate whether insulin influences the progression of colitis. Colonic tissues, the host metabolome and the gut microbiome were analyzed to investigate the relationship among insulin treatment, the microbiome, and disease. Experiments involving antibiotic (Abx) treatment and fecal microbiota transplantation (FMT) confirmed the association among the gut microbiota, insulin and IBD. In a series of experiments, we further defined the mechanisms underlying the anti-inflammatory effects of insulin. RESULTS: We found that low-dose insulin treatment alleviated intestinal inflammation but did not cause death. These effects were dependent on the gut microbiota, as confirmed by experiments involving Abx treatment and FMT. Using untargeted metabolomic profiling and 16S rRNA sequencing, we discovered that the level of the secondary bile acid lithocholic acid (LCA) was notably increased and the LCA levels were significantly associated with the abundance of Blautia, Enterorhadus and Rumi-NK4A214_group. Furthermore, LCA exerted anti-inflammatory effects by activating a G-protein-coupled bile acid receptor (TGR5), which inhibited the polarization of classically activated (M1) macrophages. CONCLUSION: Together, these data suggest that insulin alters the gut microbiota and affects LCA production, ultimately delaying the progression of IBD.

Polydatin alleviates mycoplasma pneumoniae-induced injury via inhibition of Caspase-1/GSDMD-dependent pyroptosis.

Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS-2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.

Correlation of R2* with fat fraction and bone mineral density and its role in quantitative assessment of osteoporosis.

OBJECTIVES: To investigate the correlation of R2* with vertebral fat fraction (FF) and bone mineral density (BMD), and to explore its role in the quantitative assessment of osteoporosis (OP). METHODS: A total of 83 patients with low back pain (59.77 ± 7.46 years, 30 males) were enrolled, which underwent lumbar MRI in IDEAL-IQ sequences and quantitative computed tomography (QCT) scanning within 48h. The FF, R2*, and BMD of all 415 lumbar vertebrae were respectively measured. According to BMD, all vertebrae were divided into BMD normal, osteopenia, and OP groups, and the difference of FF and R2* among groups was analyzed by one-way ANOVA. The correlation between R2*, FF, and BMD was analyzed by Pearson's test. Taking BMD as the gold standard, the efficacies for FF and R2* in diagnosis of OP and osteopenia were assessed by receiver operating characteristic curve, and their area under the curve (AUC) was compared with DeLong's test. RESULTS: The FF and R2* were statistically different among groups (F values of 102.521 and 11.323, both p < 0.05), and R2* were significantly correlated with FF and BMD, respectively (r values of -0.219 and 0.290, both p < 0.05). In diagnosis of OP and osteopenia, the AUCs were 0.776 and 0.778 for FF and 0.638 and 0.560 for R2*, and the AUCs of R2* were lower than those of FF, with Z values of 4.030 and 4.087, both p < 0.001. CONCLUSION: R2* is significantly correlated with FF and BMD and can be used as a complement to FF and BMD for quantitative assessment of OP. KEY POINTS: • R2* based on IDEAL-IQ sequences has a definite but weak linear relationship with FF and BMD. • FF is significantly correlated with BMD and can effectively evaluate BMAT. • R2* can be used as a complement to FF and BMD for fine quantification of bone mineral loss and bone marrow fat conversion.

Quantitative Study of Vertebral Body and Paravertebral Muscle Degeneration Based on Dual-Energy Computed Tomography: Correlation With Bone Mineral Density.

OBJECTIVES: This study aimed to quantify the degeneration of the vertebral body and paravertebral muscles using dual-energy computed tomography (DECT) and study its relationship with osteoporosis. METHODS: A total of 130 patients with chronic low back pain were included in this study, and DECT scanning of the lumbar region was undertaken prospectively. By placing a standard quantitative computed tomography corrected phantom under the waist during the DECT procedure, bone mineral density (BMD) and the following quantitative parameters were obtained: calcium density (CaD), vertebral fat fraction (VFF), psoas major area, psoas major fat fraction, erector spinalis area, and erector spinalis fat fraction (ESFF). Independent sample t test and 1-way analysis of variance were used between different age-BMD groups. Pearson test was applied to determine correlations for all measurements, and a mathematical model of BMD was established through regression analysis. RESULTS: Calcium density, VFF, psoas major area, psoas major fat fraction, erector spinalis area, and ESFF were significantly different among the age-BMD groups (P < 0.05), and BMD was significantly correlated with these parameters (P < 0.05). Calcium density, VFF, and ESFF were included in the BMD regression equation: BMD = 69.062 + 11.637 × CaD - 1.018 × VFF - 0.726 × ESFF (R2 = 0.860, F = 125.979, P < 0.001). CONCLUSIONS: Degeneration of the vertebral body and paravertebral muscles can be quantitatively analyzed using DECT, and CaD, VFF, and ESFF were independent influencing factors of BMD.

Hepatic Steatosis: CT-Based Prevalence in Adults in China and the United States and Associations With Age, Sex, and Body Mass Index.

BACKGROUND. Calibrated CT fat fraction (FFCT) measurements derived from un-enhanced abdominal CT reliably reflect liver fat content, allowing large-scale population-level investigations of steatosis prevalence and associations. OBJECTIVE. The purpose of this study was to compare the prevalence of hepatic steatosis, as assessed by calibrated CT measurements, between population-based Chinese and U.S. cohorts, and to investigate in these populations the relationship of steatosis with age, sex, and body mass index (BMI). METHODS. This retrospective study included 3176 adults (1985 women and 1191 men) from seven Chinese provinces and 8748 adults (4834 women and 3914 men) from a single U.S. medical center, all drawn from previous studies. All participants were at least 40 years old and had undergone unenhanced abdominal CT in previous studies. Liver fat content measurements on CT were cross-calibrated to MRI proton density fat fraction measurements using phantoms and expressed as adjusted FFCT measurements. Mild, moderate, and severe steatosis were defined as adjusted FFCT of 5.0-14.9%, 15.0-24.9%, and 25.0% or more, respectively. The two cohorts were compared. RESULTS. In the Chinese and U.S. cohorts, the median adjusted FFCT for women was 4.7% and 4.8%, respectively, and that for men was 5.8% and 6.2%, respectively. In the Chinese and U.S. cohorts, steatosis prevalence for women was 46.3% and 48.7%, respectively, whereas that for men was 58.9% and 61.9%, respectively. Severe steatosis prevalence was 0.9% and 1.8% for women and 0.2% and 2.6% for men in the Chinese and U.S. cohorts, respectively. Adjusted FFCT did not vary across age decades among women or men in the Chinese cohort, although it increased across age decades among women and men in the U.S. cohort. Adjusted FFCT and BMI exhibited weak correlation (r = 0.312-0.431). Among participants with normal BMI, 36.8% and 38.5% of those in the Chinese and U.S. cohorts, respectively, had mild steatosis, and 3.0% and 1.5% of those in the Chinese and U.S. cohorts, respectively, had moderate or severe steatosis. Among U.S. participants with a BMI of 40.0 or greater, 17.7% had normal liver content. CONCLUSION. Steatosis and severe steatosis had higher prevalence in the U.S. cohort than in the Chinese cohort in both women and men. BMI did not reliably predict steatosis. CLINICAL IMPACT. The findings provide new information on the dependence of hepatic steatosis on age, sex, and BMI.

Kukoamine A inhibits C-C motif chemokine receptor 5 to attenuate lipopolysaccharide-induced lung injury.

The aim of this study was to elucidate the mechanism underlying the effects of Kukoamine A (KuA) treatment on endotoxin-induced lung injury/inflammation. The study was performed in lipopolysaccharide (LPS)-exposed mouse models of lung injury and LPS-induced alveolar epithelial cell model. Relevant kits were used to detect levels of inflammation-related indicators, oxidative stress indicators, and mitochondrial function. Hematoxylin and eosin staining was to detect lung injury. Then, C-C motif chemokine receptor 5 (CCR5) overexpression plasmid was transfected into alveolar epithelial cells to investigate the mechanism of KuA in lung injury. The results showed that LPS induction increased the expression of inflammatory factors, oxidative stress markers, and mitochondrial dysfunction in both animal and cellular models. In the mouse model, KuA treatment improved lung tissue injury, decreased wet-to-dry ratio and MPO levels, reduced the expression of inflammatory factors, and ameliorated oxidative stress and mitochondrial dysfunction. The protective effect of KuA in the cell model remained whereas was markedly reversed after CCR5 overexpression. Taken together, KuA might improve LPS-induced lung injury by inhibiting CCR5. This might also provide a novel theory for KuA in the treatment of lung injury.

Dual-Energy Computed Tomography Virtual Noncalcium Technique in Diagnosing Osteoporosis: Correlation With Quantitative Computed Tomography.

OBJECTIVE: The aim of this study was to evaluate dual-energy computed tomography (CT) virtual noncalcium (VNCa) technique as a means of quantifying osteoporosis. METHODS: Dual-energy CT scans were obtained prospectively, targeting lumbar regions of 55 patients with chronic low back pain. A standard quantitative CT (QCT) phantom was positioned at the waist during each procedure, using proprietary software (QCT Pro; Mindways, Tex) to measure bone mineral density (BMD) in each vertebral body. Vendor dual-energy analytic software was altered with a specially modified configuration file to produce a "Virtual Non Calcium" or "VNCa" output, as such output variables were remapped to produce the following calcium values rather than iodine, yielding the following QCT parameters: CT value of calcium (originally "contrast media" [CM]), CT value of mixed energy imaging (regular CT value [rCT]), calcium density (originally "contrast agent density" [CaD]), and fat fraction (FF). Pearson test served to assess correlations between BMD and these parameters. Multiple linear regression analysis was applied to construct an equation for generating regressive BMD (rBMD) values. In gauging diagnostic accuracies, the criterion-standard BMD cutoff point (<80 mg/cm3) was adopted for QCT, whereas the rBMD threshold was defined by receiver operating characteristic curve. RESULTS: Contrast media, rCT, CaD, and FF values (reflecting CT value of calcium, regular CT value, calcium density, and fat fraction, respectively) significantly correlated with BMD (r values: 0.885, 0.947, 0.877, and 0.492, respectively; all P < 0.01). Contrast media, CaD, and FF showed independent associations with BMD; the regressive equation was formulated as follows: rBMD = 54.82 - 0.19 × CM + 20.03 × CaD - 1.24 × FF. The area under the curve of rBMD in diagnosing osteoporosis was 0.966 ± 0.009 (P < 0.01). At an rBMD threshold of less than 81.94 mg/cm3, sensitivity and specificity were 90.0% and 92.0%, respectively. CONCLUSIONS: Dual-energy CT VNCa technique may constitute a valid alternative method for quantifying the mineral content and marrow fat composition of bone in diagnostic assessments of osteoporosis.

Percentage fat fraction in magnetic resonance imaging: upgrading the osteoporosis-detecting parameter.

BACKGROUND: Osteoporosis (OP) is a systemic metabolic bone disorder identified as an essential health issue worldwide. Orthopedic imaging approaches were commonly used with some limitations. Thus, our study aimed to investigate the diagnostic value of magnetic resonance spectroscopy (1-H MRS) and m-Dixon-Quant in OP. METHODS: A total of 76 subjects were enrolled in the study and bone mineral density (BMD) was measured using quantitative computed tomography (QCT). Then, the subjects were divided into three groups according to BMD: normal control group, osteopenia group and OP group. The following parameters were recorded for each patient: gender, age, height, body weight, waist circumference, and hip circumference. Further, the fat fraction percentage (FF%) values were determined by 1-H MRS and m-Dixon-Quant methods. RESULTS: In both 1-H MRS and magnetic resonance Imaging (MRI) m-Dixon-Quant, the FF% exhibited a negative correlation with BMD (P < 0.05). The FF% value of the OP group was significantly higher than that of the control group (P < 0.05). In addition, the FF% value in the m-Dixon scans was positively related to age, while BMD showed a negative linear relationship with age (P < 0.0001). Further, females had a significantly higher FF% value compared to males (P < 0.01), and height was correlated with BMD (P < 0.05) but not with FF% (P > 0.05). CONCLUSIONS: MRI investigations especially FF% value in the m-Dixon-Quant imaging system is correlated with OP. Its diagnostic value remains to be demonstrated on a large prospective cohort of patients. Besides, parameters such as age, gender, and height are important factors for predicting and diagnosing OP.

Meta-analysis of Chinese medicine in the treatment of adenoidal hypertrophy in children.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine in the treatment of adenoid hypertrophy in children. METHOD: Screening standard articles, extracting relevant data from meta-analysis, were analyzed by Revman5.1 software, by searching PubMed, Medline, VIP, Wan Fang and Chinese HowNet database 2006-2016 in traditional Chinese medicine treatment of children with adenoid literature. RESULTS: 206 articles met the inclusion criteria, of which ten were selected and included in the meta-analysis, and there were 803 patients. The results showed that the remission rate of the Chinese medicine treatment group was better than that of the Western medicine group. The combined effect of the amount of OR 2.06, 95% Cl (1.45, 2.96) and the combined effect of the amount of the test Z = 4.12, P < 0.00001 showed the recurrence of the disease was lower in traditional Chinese medicine treatment group than the Western medicine group. The combined effect of the amount of OR 3.05, 95% Cl (2.11, 4.56) and the combined effect of the amount of the test Z = 5.86, P < 0.00001 showed the total effective rate is high in the traditional Chinese medicine treatment group than the Western medicine group. The difference between the combined effect of the amount of OR 2.79, 95% Cl (1.78, 5.03) and the combined effect of the amount of the test of Z = 4.54, P < 0.00001 was statistically significant, which showed the treatment effect of Chinese medicine group is obviously better than the Western medicine group. CONCLUSION: The use of Chinese medicine for the treatment of children with adenoid hypertrophy has good clinical efficacy.

[Idiopathic mesenteric phlebosclerosis: one case report and literature review].

Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease and it is easy to be misdiagnosed, which is characterized by intestinal obstruction symptoms, such as abdominal pain, bloating and vomiting. In this study, a case of IMP was observed and the literatures were reviewed. Computed tomography shows funicular high-density shadow and vascular calcification shadow along the vessels around the bowels. Narrow band imaging (M-NBI) endoscopy revealed the disappeared honeycomb capillary, the disordered microvascular structure and the increased density of blood vessels.

Morphological studies of cartilage endplates in subaxial cervical region.

PURPOSE: The aim of this study was to provide morphological data of endplates for the redesign of cervical artificial disc for use in the middle and lower cervical spine (C3-C7). METHODS: Reformatted CT scans of 73 individuals were analysed. The shapes of superior endplates (SEPs) and inferior endplates (IEPs) were classified as either flat or arced. The curvature radius of the IEP and sagittal disc angle were measured in the mid-sagittal plane. The maximum transverse diameter (MTD) of the SEPs and IEP was measured in the coronal plane. RESULTS: The majority of SEPs were flat (79.5 % at C7 and 91.8-95.9 % at C3-C6). Almost all (98.6-100 %) IEPs were arced. The curvature radius has a gradually increasing trend from C3 to C6 (P < 0.05, mean 29.26 mm). There were significant differences at C3-C7 in the average sagittal disc angles (5.80°, 6.92°, 7.51°, and 8.82°, respectively; P < 0.05; mean 7.26°), the average MTDs of the SEPs (13.64, 14.42, 15.03, and 16.74 mm, respectively, P < 0.05; mean 14.96 mm) and the average MTD of the IEPs (16.77, 17.67, 19.15, and 21.66 mm, respectively; P < 0.05; mean 18.81 mm). CONCLUSION: The majority of SEPs were flat, while almost all IEPs were curved. The curvature radius of IEPs has a gradually increasing trend from C3 to C6. The average sagittal disc angles, MTDs of the SEPs and IEPs significantly increased from C3 to C7. Based on the above, the current cervical artificial disc design does not sufficiently match the morphology of cervical endplates (CEPs). This mismatch may lead to some postoperative complications of cervical disc arthroplasty.

Effect of inhibiting malonyl-CoA decarboxylase on cardiac remodeling after myocardial infarction in rats.

OBJECTIVES: The objective of this study was to determine the effect of inhibiting malonyl-CoA decarboxylase (MCD) on cardiac remodeling following myocardial infarction (MI) in rats. We used an ultrasound (US)-mediated microbubble (MB) approach for targeted delivery of a microRNA (miRNA) interference plasmid to the myocardium to silence MCD expression. METHODS: Five pairs of RNA interference sequences were screened and ranked according to their highest inhibition rates in HEK293 cells. The plasmid with the highest inhibition rate was transfected by US into the rat myocardium after mixing with lipid MB. Twelve and 16 weeks after MI, cardiac function was measured by echocardiography, and glucose transporter-4 (GLUT-4) and high-energy phosphate levels were monitored in the myocardium before and after transfection. RESULTS: Ejection fraction (EF) decreased by 16% in the control MI group, while it decreased by 8% in the MCD inhibition group that utilized the US-mediated MB approach. Concomitant with the improved EF, high-energy phosphates were increased and lactic acid was decreased in the left ventricle (LV), with no changes in triglyceride or GLUT-4 levels. CONCLUSIONS: Inhibiting MCD by an US-mediated injection of miRNA into the rat myocardium increased energy reserves in the LV after MI, most likely by limiting lactic acidosis and improving cardiac function without increasing lipid toxicity.

The height for screw index (HSI) predicts the development of C2 nerve dysfunction associated with C1 lateral mass screw fixation for atlantoaxial instability.

PURPOSE: To propose a new measure, the height for screw index (HSI), as a predictor of C2 nerve dysfunction in patients who have received posterior C1 lateral mass screw (C1LMS) fixation for atlantoaxial instability and to examine whether the HSI scores correlated with the development of C2 nerve dysfunction through retrospective analysis of 104 C1LMS inserted in 52 patients with atlantoaxial instability. METHODS: The medical records of patients who underwent C1LMS fixation were retrospectively reviewed. C1LMS, 3.5 mm in diameter, was inserted for atlantoaxial stabilization. The sagittal plane of the planned C1LMS trajectory was reconstructed from CT images. The HSI was defined as the difference in height between C2 ganglion and its corresponding foramen. C2 nerve function was assessed using a validated visual analog scale questionnaire. Each foramen receiving C1LMS was considered as a single unit and patients were categorized to group 1, HSI ≥4.0 mm; group 2, HSI <4.0 mm. RESULTS: The mean HSI score was 4.7 ± 0.8 mm (range 3.1-6.5 mm) with 85 (81.7 %) units in group 1, and 19 (18.3 %) units in group 2. Fourteen (13.5 %, 14/104) units developed C2 nerve dysfunction. C2 nerve dysfunction was reported in 4 units in group 1, and 10 units in group 2, respectively. The percentage of C2 nerve dysfunction was significantly higher in group 2 than that in group 1 (P < 0.001, Pearson Chi-square test). CONCLUSIONS: The HSI score correlates with the development of C2 nerve dysfunction in patients receiving C1LMS fixation for atlantoaxial instability and may be a useful predictor of C2 nerve dysfunction.

Morphology of the atlas pedicle revisited: a morphometric CT-based study on 120 patients.

PURPOSE: To quantify the dimensions of the atlas pedicles and to analyze the relationship between extra medullary height (EMH) with intra medullary height (IMH) of the atlas pedicle. METHODS: The images of the patients who had CT scanning and three-dimensional (3D) reconstruction involving atlantoaxial complex between June 2011 and April 2012 and meet our inclusion criteria were studied retrospectively. After reformatting the original images, the EMH and IMH of the atlas pedicles were measured. RESULTS: Extra medullary height and IMH were, respectively, 4.83 ± 1.13 and 1.29 ± 1.10 mm for males and 3.75 ± 0.93 and 0.60 ± 0.83 mm for females, with statistical difference (P < 0.05). EMH and IMH had some correlation (correlation coefficient r = 0.804) but showed a large variability. Of 240 pedicles of 120 cases, 47.92% (115 pedicles) were ≥1 mm; 12.08% (29 pedicles) were between 0 and 1 mm; and 40% (96 pedicles) were 0. CONCLUSION: The EMH and the IMH of the atlas pedicles were measured by using CT images of the atlas, providing anatomic parameters for surgery. They showed a certain correlation but with a high variability. C1 pedicle screw fixation was well performed when the medullary canal was ≥1 mm, but the surgical procedure should be careful when it was between 0 and 1 mm, and avoided when there was no medullary canal in the atlas pedicle! So 3D CT reconstruction should be conducted to obtain data and establish individualized fixation strategy preoperatively.

A cross-sectional study of the clinical characteristics of hospitalized children with community-acquired pneumonia in eight eastern cities in China.

BACKGROUND: Community-acquired pneumonia in children is common in China. To understand current clinical characteristics and practice, we conducted a cross-sectional study to analyze quality of care on childhood pneumonia in eight eastern cities in China. METHODS: Consecutive hospital records between January 1, 2010 and December 31, 2010 were collected from 13 traditional Chinese medicine (TCM) and western medicine (WM) hospitals in February, May, August, and November (25 cases per season, 100 cases over the year), respectively. A predesigned case report form was used to extract data from the hospital medical records. RESULTS: A total of 1298 cases were collected and analyzed. Symptoms and signs upon admission at TCM and WM hospitals were cough (99.3% vs. 98.6%), rales (84.8% vs. 75.0%), phlegm (83.3% vs. 49.1%), and fever (74.9% vs. 84.0%) in frequency. Patients admitted to WM hospitals had symptoms and signs for a longer period prior to admission than patients admitted to TCM hospitals. Testing to identify etiologic agents was performed in 1140 cases (88.4%). Intravenous antibiotics were administered in 99.3% (595/598) of cases in TCM hospitals and in 98.6% (699/700) of cases in WM hospitals. Besides, Chinese herbal extract injection was used more frequently in TCM hospitals (491 cases, 82.1%) than in WM hospitals (212 cases, 30.3%) (p < 0.01). At discharge, 818 cases (63.0%) were clinically cured, with a significant difference between the cure rates in TCM (87.6%) and WM hospitals (42.0%) (OR = 9.8, 95% confidence interval (CI): 7.3 ~ 12.9, p < 0.01). Pathogen and previous medical history were more likely associated with the disappearance of rales (OR = 7.2, 95% CI: 4.8 ~ 10.9). Adverse effects were not reported from the medical records. CONCLUSIONS: Intravenous use of antibiotics is highly prevalent in children with community-acquired pneumonia regardless of aetiology. There was difference between TCM and WM hospitals with regard to symptom profile and the use of antibiotics. Intravenous use of herbal injection was higher in TCM hospitals than in WM hospitals. Most of the cases were diagnosed based on clinical signs and symptoms without sufficient confirmation of aetiology. Audit of current practice is urgently needed to improve care.

Short working hours and perceived stress: Findings from a population-based nationwide study.

Background: Evidence on the potential negative health effects of short working hours remains limited. This study aimed to investigate the association between short working hours and perceived stress in a population-based sample from China. Methods: This cross-sectional study included 4368 participants aged 18-65 years from the China Health and Nutrition Surveys (CHNS) 2015. Working hours were categorized into <35, 35-40, 41-54, and ≥55 h/week. Perceived stress was assessed using the Perceived Stress Scale-14 (PSS-14). Results: Of the 4368 participants, 817 (18.7 %) reported short working hours (<35 h/week) and 1817 (41.6 %) reported perceived stress. Short working hours were associated with higher perceived stress compared to standard working hours (35-40 h/week) (Adjusted odds ratios (AOR) = 1.25, 95 % confidential intervals (CI): 1.04-1.51). Stratified analysis showed that short working hours were significantly associated with more perceived stress in subjects aged 36-50 years (AOR = 1.43, 95 % CI: 1.16-1.70), while long working hours (≥55 h/week) were significantly related to less perceived stress among low-income subjects (AOR = 0.56, 95 % CI: 0.33-0.94). Reduced income partially mediated the effects of short working hours on perceived stress (indirect effects = -0.002, 95 % CI: -0.007∼-0.001). Conclusion: Reduced working hours may be associated with increased risk of perceived stress in China, particularly among people aged 36-50 years and those with low income. Reduced income may be a possible reason for the increased perceived stress caused by short working hours. Future longitudinal studies are needed to examine these relationships and to explore mechanisms.

Modulation of miR-146b by N6-methyladenosine modification remodels tumor-associated macrophages and enhances anti-PD-1 therapy in colorectal cancer.

PURPOSE: MicroRNA-146b (miR-146b) alleviates experimental colitis in mice by mediating macrophage polarization and the release of inflammatory factors. Our goals were to evaluate the antitumor efficacy of miR-146b in colorectal cancer (CRC) and to investigate the underlying mechanisms. METHODS: We used murine models of CRC to evaluate whether miR-146b influenced the progression of tumors independent of tumor-associated macrophages (TAMs). RNA immunoprecipitation, N6-methyladenosine (m6A) RNA immunoprecipitation and in vitro pri-miRNA processing assays were conducted to examine whether m6A mediates the maturation of pri-miR-146b/miR-146b. In a series of in vitro and in vivo experiments, we further defined the molecular mechanisms of methyltransferase-like 3 (METTL3)/miR-146b-mediated antitumor immunity and its efficacy in combination with anti-PD-1 immunotherapy. RESULTS: We found that miR-146b deletion supported tumor progression by increasing the number of alternatively activated (M2) TAMs. Mechanistically, the m6A-related "writer" protein METTL3 and "reader" protein HNRNPA2B1 controlled miR-146b maturation by regulating the m6A modification region of pri-miR-146b. Furthermore, miR-146b deletion promoted the polarization of M2-TAMs by enhancing phosphoinositide 3-kinase (PI3K)/AKT signaling, and this effect was mediated by the class IA PI3K catalytic subunit p110ß, which reduced T cell infiltration, aggravated immunosuppression and ultimately promoted tumor progression. METTL3 knockdown or miR-146b deletion induced programmed death ligand 1 (PD-L1) production via the p110ß/PI3K/AKT pathway in TAMs and consequently augmented the antitumor activity of anti-PD-1 immunotherapy. CONCLUSIONS: The maturation of pri-miR-146b is m6A-dependent, and miR-146b deletion-mediated TAM differentiation promotes the development of CRC by activating the PI3K/AKT pathway, which induces upregulation of PD-L1 expression, inhibits T cell infiltration into the TME and enhances the antitumor activity of anti-PD-1 immunotherapy. The findings reveal that targeting miR-146b can serve as an adjuvant to anti-PD-1 immunotherapy.

Inulin intervention attenuates hepatic steatosis in rats via modulating gut microbiota and maintaining intestinal barrier function.

Increasing evidence has suggested the mitigatory efficacy of prebiotic inulin on nonalcoholic fatty liver disease (NAFLD), nevertheless, its action mechanisms remain elusive. Herein, inulin consumption effectively ameliorated high-sucrose diet-induced hepatic steatosis and inflammation, and rehabilitated liver lipogenesis regulators, including carbohydrate response element-binding protein, stearoyl-CoA desaturase-1 and peroxisome proliferator-activated receptor alpha. Furthermore, inulin supplementation restored the intestinal barrier integrity and function by up-regulating expressions of tight junction proteins (zonula occludens-1, claudin-1 and occludin). High-throughput sequencing demonstrated that inulin administration regulated the gut microbiota composition, wherein abundance of short-chain fatty acid (SCFA)-producers, including Bifidobacterium, Phascolarctobacterium and Blautia, was significantly enhanced in the inulin-treated rats, conversely, opportunistic pathogens, such as Acinetobacter and Corynebacterium_1, were suppressed. SCFA quantitative analysis showed that dietary inulin suppressed faecal acetate levels, but improved propionate and butyrate concentrations in rats with NAFLD. Functional prediction showed that tryptophan metabolism was one of the key metabolic pathways affected by gut microbiota changes. A targeted metabolomics profiling of tryptophan metabolism demonstrated that inulin intervention up-regulated faecal contents of indole-3-acetic acid and kynurenic acid, whereas down-regulated levels of kynurenine and 5-hydoxyindoleacetic acid in NAFLD rats. Therefore, this study demonstrated that inulin intake alleviated hepatic steatosis likely by regulating the gut microbiota composition and function and restoring the intestinal barrier integrity, which may provide a novel notion for the prevention and treatment of NAFLD in future.

Retraction: application of hybrid particle swarm and ant colony optimization algorithms to obtain the optimum homomorphic wavelet image fusion.

[This retracts the article DOI: 10.21037/atm-20-5997.].

Nonlinear dependence between China's carbon market and stock market: new evidence from quantile coherency and causality-in-quantiles.

This study examines the nonlinear dependence between carbon market and stock market in China under normal and extreme market conditions by employing two novel nonlinear approaches, namely, quantile coherency and causality-in-quantiles methods. Given our results on the overall and sector level of stock market, we find that there is a negative dependence between the two markets under bearish and normal market states in the short- and medium-term respectively, while the dependence becomes positive under bearish and bullish market states in the long-term. Furthermore, we also prove that the Granger causality from carbon market to stock market exists. However, no evident impacts from stock market to carbon market have been found. Additionally, at sector stock market, we discover heterogeneity across market conditions. And emission-intensive sector stock indices are more affected by carbon prices.