Development and validation of a risk prediction model for the recurrence of foot ulcer in type 2 diabetes in China: A longitudinal cohort study based on a systematic review and meta-analysis.

AIMS: To develop and validate a risk prediction model for Chinese patients with type 2 diabetes with the recurrence of diabetic foot ulcers (DFUs) based on a systematic review and meta-analysis. METHODS: A prospective analysis was performed with 1333 participants and followed up for 60 months. Three models were analysed using a derived cohort. The risk factors were screened using meta-analysis and logistic regression, and the missing variables were interpolated by multiple imputation. The internal validation was performed using the bootstrap procedure, and the validation cohort was applied to the external validation. The performance of the model was evaluated in the area under the discrimination Receiver Operating Characteristic Curve (ROC). Calibration and discrimination methods were used for the validation cohort. The variables were selected according to their clinical and statistical importance to construct the nomograms. RESULTS: Three models were developed and validated. Model 1 included seven social and clinical indicators like sex, diabetes mellitus duration, previous DFU, location of ulcer, smoking, history of amputation, and foot deformity. Model 2 included four more indicators besides those in Model 1, which were statin agents used, antiplatelet agents used, systolic blood pressure, and body mass index. Model 3 added further laboratory indicators to Model 2, such as LDL-C, HbA1C, fibrinogen, and blood urea nitrogen. In the derivation cohort, 20.1% (206/1027) participants with DFU recurred as compared to the validation cohort, which was 38.2% (117/306). The areas under the curve in the derivation cohort for Models 1-3 were 0.781 (0.744-0.817), 0.843 (0.813-0.873), and 0.899 (0.876-0.922), respectively. The Youden indexes for Models 1-3 were 0.430, 0.559, and 0.653, respectively. Model 3 showed the highest sensitivity and specificity. All models performed well for both discrimination and calibration. CONCLUSIONS: Models 1-2 were non-invasive, which indicate their role in general screening for patients at a high risk of recurrence of DFU. However, Model 3 offers a more specific screening due to its best performance in predicting the risk of DFU recurrence amongst the three models.

Integrating scRNA-seq to explore novel macrophage infiltration-associated biomarkers for diagnosis of heart failure.

OBJECTIVE: Inflammation and immune cells are closely intertwined mechanisms that contribute to the progression of heart failure (HF). Nonetheless, there is a paucity of information regarding the distinct features of dysregulated immune cells and efficient diagnostic biomarkers linked with HF. This study aims to explore diagnostic biomarkers related to immune cells in HF to gain new insights into the underlying molecular mechanisms of HF and to provide novel perspectives for the detection and treatment of HF. METHOD: The CIBERSORT method was employed to quantify 22 types of immune cells in HF and normal subjects from publicly available GEO databases (GSE3586, GSE42955, GSE57338, and GSE79962). Machine learning methods were utilized to screen for important cell types. Single-cell RNA sequencing (GSE145154) was further utilized to identify important cell types and hub genes. WGCNA was employed to screen for immune cell-related genes and ultimately diagnostic models were constructed and evaluated. To validate these predictive results, blood samples were collected from 40 normal controls and 40 HF patients for RT-qPCR analysis. Lastly, key cell clusters were divided into high and low biomarker expression groups to identify transcription factors that may affect biomarkers. RESULTS: The study found a noticeable difference in immune environment between HF and normal subjects. Macrophages were identified as key immune cells by machine learning. Single-cell analysis further showed that macrophages differed dramatically between HF and normal subjects. This study revealed the existence of five subsets of macrophages that have different differentiation states. Based on module genes most relevant to macrophages, macrophage differentiation-related genes (MDRGs), and DEGs in HF and normal subjects from GEO datasets, four genes (CD163, RNASE2, LYVE1, and VSIG4) were identified as valid diagnostic markers for HF. Ultimately, a diagnostic model containing two hub genes was constructed and then validated with a validation dataset and clinical samples. In addition, key transcription factors driving or maintaining the biomarkers expression programs were identified. CONCLUSION: The analytical results and diagnostic model of this study can assist clinicians in identifying high-risk individuals, thereby aiding in guiding treatment decisions for patients with HF.

Synergistic anti-inflammatory effect of gut microbiota and lithocholic acid on liver fibrosis.

BACKGROUND: Bile acids can regulate liver disease progression by affecting the functions of gut microbiota and immune cells. As the most potent natural agonist of G-protein coupled bile acid receptor 5 (TGR5) (expressed in macrophages, HSCs, and monocytes), lithocholic acid (LCA) has multiple functions, such as inhibiting inflammation and regulating metabolism. Therefore, this study aims to investigate the effects of LCA on immune cells and HSCs in liver fibrosis. METHODS: A liver fibrosis mouse model was induced by carbon tetrachloride followed by gavage of LCA, and the effects of LCA were evaluated by serum biochemical analysis, liver histology, and western bolt. Plasma cytokine levels and the number of immune cells were determined by cytometric bead array and flow cytometry, respectively. RESULTS: LCA could inhibit the activation of HSCs by inducing apoptosis and reducing the activation of transforming growth factor-ß (TGF-ß) Smad-dependent and Smad-independent pathways. Meanwhile, LCA inhibited glycolysis and promoted oxidative phosphorylation, leading to the differentiation of macrophages to M2 type and inhibiting their differentiation to M1 type. Furthermore, LCA increased the recruitment of NK cells and reduced the activation of NKT cells. However, these effects of LCA were attenuated after antibiotics reduced the diversity and abundance of the gut microbiota. CONCLUSIONS: Gut microbiota and LCA exerted synergistic anti-inflammatory effects on liver fibrosis. The combined intervention of gut microbiota and LCA will be a new strategy for treating liver fibrosis.

Longitudinal associations between household solid fuel use and depression in middle-aged and older Chinese population: A cohort study.

BACKGROUND: Previous studies found that ambient air pollution was associated with a higher prevalence of depressive symptoms. However, the longitudinal associations between household solid fuel use, which is the main source of household air pollution, and depressive symptoms remain unclear. This cohort study aimed to explore the associations between household solid fuel use and incidence of depressive symptoms in China. METHODS: In total, 8637 participants were enrolled in this prospective cohort study. Depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale. The associations between baseline household solid fuel use and the incidence of depressive symptoms were examined using Cox proportional hazards regression models. RESULTS: During the 4-year of follow-up, 2074 of 8637 participants developed depressive symptoms. Compared with participants who used clean fuel for both heating and cooking, the multivariate-adjusted hazard ratio (HR) (95% confidence intervals [95% CI]) for depressive symptoms incidence in participants who used solid fuels for two purposes (cooking and heating) was 1.15 (1.01, 1.31). In the solid fuel use subgroup analysis, use of solid fuels for cooking (HR, 1.12; 95% CI, 1.02-1.24) was associated with a higher incidence of depressive symptoms after adjustments while use for heating (HR, 1.05; 95% CI, 0.93-1.18) was not. Moreover, compared with persistent solid fuel users, switching from solid to clean fuels for cooking resulted in a lower risk of depressive symptoms before adjustments (HR, 0.82; 95% CI, 0.71-0.95) and a non-significant association (HR, 0.90; 95% CI, 0.77-1.04) afterwards. CONCLUSIONS: The results suggest that household solid fuel use for cooking was associated with a higher incidence of depressive symptoms. Preventive strategies based on improving household cooking environment for depressive symptoms should be established.

Identification of biomarkers correlated with hypertrophic cardiomyopathy with co-expression analysis.

Hypertrophic cardiomyopathy (HCM) is reported to be the most common genetic heart disease. To identify key module and candidate biomarkers correlated with clinical prognosis of patients with HCM, we carried out this study with co-expression analysis. To construct a co-expression network of hub genes correlated with HCM, the Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network analysis of central genes was performed to recognize the interactions of central genes. Gene set enrichment analyses were carried out to discover the possible mechanisms involved in the pathways promoted by hub genes. To validate the hub genes, quantitative real-time polymerase chain reaction (RT-PCR) was performed. Based on the results of topological overlap measure based clustering, 2,351 differentially expressed genes (DEGs) were identified. Those genes were included in six different modules. Of these modules, the yellow and the blue modules showed a pivotal correlation with HCM. DEGs were enriched in immune system procedure associated GO terms and KEGG pathways. We identified nine hub genes (TYROBP, STAT3, CSF1R, ITGAM, SYK, ITGB2, LILRB2, LYN, and HCK) affected the immune system significantly. Among the genes we validated with RT-PCR, TYROBP, CSF1R, and SYK showed significant increasing expression levels in model HCM rats. In conclusion, we identified two modules and nine hub genes, which were prominently associated with HCM. We found that immune system may play a crucial role in the HCM. Accordingly, those genes and pathways might become therapeutic targets with clinical usefulness in the future.

Effects of Angiotensin Receptor Neprilysin Inhibitors on Inducibility of Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy.

The aims of the present study were to investigate the effects of angiotensin receptor neprilysin inhibitors (ARNi) on the susceptibility of ventricular arrhythmias (VAs) in rats with myocardial infarction (MI) and to explore the related mechanisms.A total of 32 adult male Sprague-Dawley rats were divided into 3 groups: a control group, MI group, and MI+ARNi group. MI was generated by ligation of the left anterior descending coronary artery. ARNi was given at 68 mg/kg/day for 4 weeks after MI surgery. At 4 weeks after MI, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of VAs, and echocardiography was used to evaluate cardiac function. Indicators of sympathetic neural remodeling and cardiac remodeling were detected to further explore the related mechanisms.Four weeks after MI, rats in the ARNi group exhibited low susceptibility of VAs in comparison with that in the MI group, which was coincident with the attenuation of sympathetic nerve remodeling, amelioration of cardiac fibrosis, and regulation of Cx43 expression.ARNi is effective in reducing VAs in rats with ischemic cardiomyopathy, which is associated with attenuating sympathetic nerve remodeling and myocardial fibrosis.

Pneumonia in patients with cirrhosis: risk factors associated with mortality and predictive value of prognostic models.

BACKGROUND: Cirrhosis always goes with profound immunity compromise, and makes those patients easily be the target of pneumonia. Cirrhotic patients with pneumonia have a dramatically increased mortality. To recognize the risk factors of mortality and to optimize stratification are critical for improving survival rate. METHODS: Two hundred and three cirrhotic patients with pneumonia at a tertiary care hospital were included in this retrospective study. Demographical, clinical and laboratory parameters, severity models and prognosis were recorded. Multivariate Cox regression analysis was used to identify independent predictors of 30-day and 90-day mortality. Area under receiver operating characteristics curves (AUROC) was used to compare the predictive value of different prognostic scoring systems. RESULTS: Patients with nosocomial acquired or community acquired pneumonia indicated similar prognosis after 30- and 90-day follow-up. However, patients triggered acute-on-chronic liver failure (ACLF) highly increased mortality (46.4% vs 4.5% for 30-day, 69.6% vs 11.2% for 90-day). Age, inappropriate empirical antibiotic therapy (HR: 2.326 p = 0.018 for 30-day and HR: 3.126 p < 0.001 for 90-day), bacteremia (HR: 3.037 p = 0.002 for 30-day and HR: 2.651 p = 0.001 for 90-day), white blood cell count (WBC) (HR: 1.452 p < 0.001 for 30-day and HR: 1.551 p < 0.001 for 90-day) and total bilirubin (HR: 1.059 p = 0.002 for 90-day) were independent factors for mortality in current study. Chronic liver failure-sequential organ failure assessment (CLIF-SOFA) displayed highest AUROC (0.89 and 0.90, 95% CI: 0.83-0.95 and 0.85-0.95 for 30-day and 90-day respectively) in current study. CONCLUSIONS: This study found age, bacteremia, WBC, total bilirubin and inappropriate empirical antibiotic therapy were independently associated with increased mortality. Pneumonia triggered ACLF remarkably increased mortality. CLIF-SOFA was more accurate in predicting mortality than other five prognostic models (model for end-stage liver disease (MELD), MELD-Na, quick sequential organ failure assessment (qSOFA), pneumonia severity index (PSI), Child-Turcotte-Pugh (CTP) score).

Sediment porewaters serve as a transient organic carbon pool at the land-ocean interface.

The organic carbon (OC) cycle at the land-ocean interface is an important component of the global carbon budget, yet the processes that control the transfer, transformation, and burial of OC in these regions remain poorly understood. In this work, we examined sedimentary OC (SOC) in short core sediments, dissolved inorganic carbon (DIC), dissolved organic carbon (DOC), and chromophoric dissolved organic matter (CDOM), as well as other solutes in sediment porewaters of the Changjiang Estuary and adjacent East China Sea (ECS) shelf. The main goal of this work is to investigate the variation of the sources and composition of different forms of carbon in estuarine sediments associated with different sedimentary regimes, to further understand the role of sediment porewater in carbon sequestration at the land-ocean interface. Concentrations of Fe2+ and Mn2+ in porewaters of the muddy sediments are much higher than those in the sandy sediments, and SO42- decreases with depth in the deep sediment layer, indicating the degradation of SOC in mobile muds is mainly driven by suboxic and/or anoxic diagenetic processes (e.g., iron-manganese reduction). The accumulation of DIC in the muddy sediment is higher compared to the sandy sediment, indicating relatively complete SOC remineralization. The DOC in porewaters of the muddy areas is mainly composed of highly degraded and low molecular weight humic-like substances (C1), whereas in the sandy area, porewater DOC is mainly composed of less degraded and high molecular weight protein-like substances (C2 and C3). The average DOC stock (28.5 t/km2) in the upper 30 cm sediment porewaters is significantly higher than that of DIC (12.5 t/km2) in sandy area, but less in muddy areas (17.0 t/km2 of DOC vs. 25.4 t/km2 of DIC). The total DOC stock in sediment porewaters of the sandy area accounted for ∼61 % of DOC stock in water column of the ECS, indicating that the porewater is an important DOC pool in the ECS. However, this DOC pool is rather transient due to its high reactivity and mobility, especially in sandy area. Nevertheless, compared with other marine environments, the carbon stock of DOC (average of 43.8 t/km2) in porewaters of stable sedimentary environments is much higher than that of DIC (average of 21.7 t/km2). This work further supports the notion that sedimentary regime plays an important role in OC cycling at the land-ocean interface and highlights the significance of sediment porewaters as a vast carbon pool in marine ecosystems.

Photodetectors Based on ZrS3/MoS2 Heterostructures.

High-performance photodetectors with the detection capability of linearly polarized light have broad applications in both military and civilian fields. Quasi-one-dimensional ZrS3 as an emerging anisotropic two-dimensional material has come under the spotlight owing to its intriguing properties. However, the performance of the ZrS3 photodetector is seriously restricted by its low responsivity. Herein, a novel high-performance photodetector based on the van der Waals ZrS3/MoS2 heterostructure is proposed. Attributed to the charge trapping-assisted photogating effect, interlayer carrier transitions, and fast spatial separation of the photogenerated electron-hole pairs, the device displays superior photoresponse characteristics ranging from the ultraviolet to the visible spectrum in terms of high responsivity up to 212 A/W, an extraordinary external quantum efficiency of 8.5 × 104%, and a prompt rise/decay time of 0.19/0.38 ms. In addition, owing to the profound birefringence and dichroism effects in ZrS3 together with strong light-matter interactions in the heterostructure, profound linear-polarization sensitivity is demonstrated with a dichroic ratio of about 2.8. Overall, this photodetector not only is integrated with the excellent properties of ZrS3 and monolayer MoS2 but also further enhances the advantages through interlayer couplings, which demonstrate the strong potential of the ZrS3-based devices for high-performance, ultrafast, and polarization-sensitive photodetection.

Automatic measurement of skin textures of the dorsal hand in evaluating skin aging.

BACKGROUND/PURPOSE: Changes in skin textures have been used to evaluate skin aging in many studies. In our previous study, we built some skin texture parameters, which can be used to evaluate skin aging of human dorsal hand. However, it will take too much time and need to work arduously to get the information from digital skin image by manual work. So, we want to build a simple and effective method to automatically count some of those skin texture parameters by using digital image-processing technology. METHODS: A total of 100 subjects aged 30 years and above were involved. Sun exposure history and demographic information were collected by using a questionnaire. The skin image of subjects' dorsal hand was obtained by using a portable skin detector. The number of grids, which is one of skin texture parameters built in our previous study, was measured manually and automatically. Automated image analysis program was developed by using Matlab 7.1 software. RESULTS: The number of grids counted automatically (NGA) was significantly correlated with the number of grids counted manually (NGM) (r = 0.9287, P < 0.0001). And in each age group, there were no significant differences between NGA and NGM. The NGA was negatively correlated with age and lifetime sun exposure, and decreased with increasing Beagley-Gibson score from 3 to 6. In addition, even after adjusting for NGA, the standard deviation of grid areas for each image was positively correlated with age, sun exposure, and Bealey-Gibson score. CONCLUSION: The method introduced in present study can be used to measure some skin aging parameters automatically and objectively. And it will save much time, reduce labor, and avoid measurement errors of deferent investigators when evaluating a great deal of skin images in a short time.

Serum levels of carbohydrate antigen 125 in patients with heart failure and obstructive sleep apnea syndrome: a retrospective analysis.

Background: Obstructive sleep apnea syndrome (OSAS) combined with heart failure (HF) has become a serious disease that threatens human health. Therapeutic interventions targeting OSAS have been shown to improve outcomes in patients with HF, so the identification of severe OSAS in HF is critical. Carbohydrate antigen 125 (CA125) is associated with inflammation and volume overload. The levels of CA125 are elevated in the serum of patients with HF and might be further elevated in patients with HF and OSAS. The aim of this study was to measure CA125 levels in patients with HF with and without OSAS and to analyze affecting factors. Methods: In this single-center retrospective cohort study, a total of 95 patients diagnosed with HF hospitalized in Zhongda Hospital from April 2021 to April 2022 were recruited, including 55 patients with OSAS and 40 patients without OSAS. Participants with a history of central sleep apnea syndrome, severe chronic obstructive pulmonary disease, tumors, severe infection, or who were pregnant were excluded. The histories of the participants were recorded, and laboratory examinations were performed. Binary logistic regression analysis was performed to determine the relationship between serum CA125 levels and OSAS in patients with HF. Results: The serum CA125 levels were higher in the HF + OSAS group than in the HF group (29.60 vs. 9.68 U/mL, P<0.001). According to the univariate analysis, CA125 (>35 U/mL) was significantly related to pleural effusion, acute HF, apnea-hypopnea index (AHI), left ventricular ejection fraction (LVEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Finally, the AHI demonstrated statistical significance in multiple analyses (OR 1.070, 95% CI: 1.019-1.124, P=0.006). Spearman rank correlation coefficient analysis showed that CA125 was positively correlated with AHI, and Ln(CA125) (Ln is the natural logarithm based on e) gradually increased with increasing AHI (r=0.551, P<0.0001). Conclusions: The levels of CA125 were further increased in patients with HF and OSAS, and CA125 (>35 U/mL) was positively correlated with AHI. As a biomarker associated with inflammation and congestion, serum CA125 may have certain value in the diagnosis of patients with HF combined with OSAS.

Automatic Gray Image Coloring Method Based on Convolutional Network.

Image coloring is a time-consuming and laborious work. For a work, color collocation is an important factor to determine its quality. Therefore, automatic image coloring is a topic with great research significance and application value. With the development of computer hardware, deep learning technology has achieved satisfactory results in the field of automatic coloring. According to the source of color information, this paper can divide automatic coloring methods into three types: image coloring based on prior knowledge, image coloring based on reference pictures, and interactive coloring. The coloring method can meet the needs of most users, but there are disadvantages such as users cannot get the multiple objects in a picture of different reference graph coloring. Aiming at this problem, based on the instance of color image segmentation and image fusion technology, the use of deep learning is proposed to implement regional mixed color more and master the method. It can be divided into foreground color based on reference picture and background color based on prior knowledge. In order to identify multiple objects and background areas in the image and fuse the final coloring results together, a method of image coloring based on CNN is proposed in this paper. Firstly, CNN is used to extract their semantic information, respectively. According to the extractive semantic information, the color of the designated area of the reference image is transferred to the designated area of the grayscale image. During the transformation, images combined with semantic information are input into CNN model to obtain the content feature map of grayscale image and the style feature map of reference image. Then, a random noise map is iterated to make the noise map approach the content feature map as a whole and the specific target region approach the designated area of the style feature map. Experimental results show that the proposed method has good effect on image coloring and has great advantages in network volume and coloring effect.

Co-interventions with Clostridium butyricum and soluble dietary fiber targeting the gut microbiota improve MAFLD via the Acly/Nrf2/NF-κB signaling pathway.

Purpose: The pathogenesis of metabolic associated fatty liver disease (MAFLD) is complex. Lipid metabolic disorder, chronic inflammation, and oxidative stress are the core events for MAFLD. Dietary intervention is an important treatment strategy for preventing the onset and progression of MAFLD. Clostridium butyricum (CB) and soluble dietary fiber (SDF) are often considered beneficial for health. We explored how two microbiota-targeted interventions (SDF and CB) influence the hepatic immune system, oxidative stress, and lipid metabolism in MAFLD mice. Methods: To explore the role of SDF and CB in MAFLD, we generated MAFLD mouse models by feeding C57BL/6 mice with a high-fat diet (HFD). After 8 weeks of intervention, we measured immune cell function, lipid metabolism, and oxidative stress levels in the livers of mice. Results: Single intervention with SDF or CB was not effective in improving MAFLD; however, co-interventions with SDF and CB increased microbiota diversity and decreased inflammation, oxidative stress, and lipid synthesis. Moreover, we determined that co-intervention with SDF and CB mediated fatty acid oxidation by activating the Acly/Nrf2/NF-κB signaling pathway. Most importantly, co-intervention exerted anti-inflammatory effects by inhibiting the differentiation of macrophages into pro-inflammatory M1 macrophages. Conclusion: This study show that co-intervention with SDF and CB can improve MAFLD, and co-intervention with  SDF and CB are suggested to be potential gut microbiota modulators and therapeutic substances for MAFLD.

Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis.

Background and Aims: Patients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism. Methods: Changes in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry. Results: The proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway. Conclusions: B cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines.

Role of bile acids in liver diseases mediated by the gut microbiome.

The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host's natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

Development and validation of an incidence risk prediction model for early foot ulcer in diabetes based on a high evidence systematic review and meta-analysis.

OBJECTIVES: To develop and validate a model for predicting the risk of early diabetic foot ulcer (DFU) based on systematic review and meta-analysis. METHODS: Data were analyzed from the risk factors of DFU with their corresponding risk ratio (RR) by meta-analysis. The DFU prediction model included statistically significant risk factors from the meta-analysis, all of which were scored by its weightings, and the prediction model was externally validated using a validation cohort from China. The occurrence of early DFU was defined as patients with type 2 diabetes who were free of DFU at baseline and diagnosed with DFU at follow-up. Evaluation of model performance was based on the area under the discrimination receiver operating characteristic curve (ROC), with optimal cutoff point determined by calculation of sensitivity and specificity. Kaplan-Meier curve were performed tocompare the cumulative risk of different groups. RESULTS: Our meta-analysis confirmed a cumulative incidence of approximately 6.0% in 46,521 patients with diabetes. The final risk prediction model included Sex, BMI, HbA1c, Smoker, DN, DR, DPN, Intermittent Claudication, Foot care, and their RRs were 1.87, 1.08, 1.21, 1.77, 2.97, 2.98, 2.76, 3.77, 0.38, respectively. The total score of all risk factors was 80 points according to their weightings. The prediction model showed good discrimination with AUC = 0.798 (95 %CI 0.738-0.858). At the optimal cut-off value of 46.5 points, the sensitivity, specificity and Youden index were 0.769, 0.798 and 0.567, respectively. The final model stratified the validation cohort into low, low-intermediate, high-intermediate and high-risk groups; Compared with low-risk group, the RR with 95 %CI of developing DFU in high-intermediate and high-risk group were 17.23 (5.12-58.02), p < 0.01 and 46.11 (5.16-91.74), p < 0.01, respectively. CONCLUSION: We have developed a simple tool to facilitates early identification of patients with diabetes at high risk of developing DFU based on scores. This simple tool may improve clinical decision-making and potentially guide early intervention.

Spatiotemporal dynamics of the archaeal community in coastal sediments: assembly process and co-occurrence relationship.

Studies of marine benthic archaeal communities are updating our view of their taxonomic composition and metabolic versatility. However, large knowledge gaps remain with regard to community assembly processes and inter taxa associations. Here, using 16S rRNA gene amplicon sequencing and qPCR, we investigated the spatiotemporal dynamics, assembly processes, and co-occurrence relationships of the archaeal community in 58 surface sediment samples collected in both summer and winter from across ~1500 km of the eastern Chinese marginal seas. Clear patterns in spatiotemporal dynamics in the archaeal community structure were observed, with a more pronounced spatial rather than seasonal variation. Accompanying the geographic variation was a significant distance-decay pattern with varying contributions from different archaeal clades, determined by their relative abundance. In both seasons, dispersal limitation was the most important process, explaining ~40% of the community variation, followed by homogeneous selection and ecological drift, that made an approximately equal contribution (~30%). This meant that stochasticity rather than determinism had a greater impact on the archaeal community assembly. Furthermore, we observed seasonality in archaeal co-occurrence patterns: closer inter-taxa connections in winter than in summer, and unmatched geographic patterns between community composition and co-occurrence relationship. These results demonstrate that the benthic archaeal community was assembled under a seasonal-consistent mechanism but the co-occurrence relationships changed over the seasons, indicating complex archaeal dynamic patterns in coastal sediments of the eastern Chinese marginal seas.

Factors associated with a SARS-CoV-2 recurrence after hospital discharge among patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. METHODS: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. RESULTS: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4+ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=-1.06, range between -1.55 and -0.57, WMD=-40.39, range between -80.20 and -0.48, and WMD=-55.26, range between -105.92 and -4.60, respectively). CONCLUSIONS: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4+ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.

Association of rs10204525 genotype GG and rs2227982 CC combination in programmed cell death 1 with hepatitis B virus infection risk.

Single nuclear polymorphism (SNP) of programmed cell death 1 (PD-1) was reported associated with hepatitis B virus (HBV) infection, but the SNP sites studied were limited. Whether the combination of 2 or more SNP sites could better represent the relationship between PD-1 SNP and HBV infection was not studied.Eight hundred ninety-eight HBV-infected patients (222 asymptomatic carriers [AsC], 276 chronic hepatitis B, 105 acute-on-chronic liver failure, and 295 liver cirrhosis) and 364 health controls of South China were enrolled in this study. Four PD-1 SNPs (rs10204525, rs2227982, rs41386349, and rs36084323) were selected and detected by TaqMan probe. The frequency of allele, genotype, and combination of different SNPs were compared between different groups.For allele frequency analysis, G allele of rs10204525 was protective factor (odds ratio (OR) = 0.823, 95% confidence interval (CI) = 0.679-0.997, P = .046) and T allele of rs2227982 was predisposing factor (OR = 1.231, 95% CI = 1.036-1.463, P = .018) in HBV infection. When analyzed in genotype frequency, the genotype GG of rs10204525 and CC of rs2227982 were protective factor of HBV infection. Combination of rs10204525 GG and rs2227982 CC was potent protective factor of HBV infection (OR = 0.552, 95% CI = 0.356-0.857, P = .007) and was also associated with lower HBV load (OR = 0.201, 95% CI = 0.056-0.728, P = .008) in AsC. The 4 SNP sites were not associated with progression of HBV-related liver disease.Rs10204525 and rs2227982 of PD-1 associate with HBV infection and combination of the 2 SNP sites can better predict host susceptibility in HBV infection.

Risk factors, clinical features, and short-term prognosis of spontaneous fungal peritonitis in cirrhosis: A matched case-control study.

BACKGROUND: Spontaneous peritonitis is one of the most common infectious complications in cirrhotic patients with ascites. Spontaneous fungal peritonitis (SFP) is a type of spontaneous peritonitis that is a less recognized but devastating complication in end-stage cirrhosis. Although high mortality was previously noted, scant data are available to fully define the factors responsible for the occurrence of SFP and its mortality. AIM: To illustrate the differences between SFP and spontaneous bacterial peritonitis (SBP) and discuss the risk factors for the occurrence of SFP and its short-term mortality. METHODS: We performed a matched case-control study between January 1, 2007 and December 30, 2018. Patients with SFP were included in a case group. Sex-, age-, and time-matched patients with SBP were included in a control group and were further divided into control-1 group (positive bacterial culture) and control-2 group (negative bacterial culture). The clinical features and laboratory parameters, severity models, and prognosis were compared between the case and control groups. Logistic regression analysis was used to determine the risk factors for occurrence, and the Cox regression model was used to identify the predictive factors for short-term mortality of SFP. RESULTS: Patients with SFP exhibited more severe systemic inflammation, higher ascites albumin and polymorphonuclear neutrophils, and a worsened 15-d mortality than patients in the control groups. Antibiotic administration (case vs control-1: OR = 1.063, 95%CI: 1.012-1.115, P = 0.014; case vs control-2: OR = 1.054, 95%CI: 1.014-1.095, P = 0.008) remarkably increased the occurrence of SFP or fungiascites. Hepatorenal syndrome (HR = 5.328, 95%CI: 1.050-18.900) and total bilirubin (µmol/L; HR = 1.005, 95%CI: 1.002-1.008) represented independent predictors of SFP-related early mortality. CONCLUSION: Long-term antibiotic administration increases the incidence of SFP, and hepatorenal syndrome and total bilirubin are closely related to short-term mortality.