Objective　A predictive model should be established during the early stages of dengue progression to evaluate the likelihood of severe dengue and dengue with warning signs, thereby preventing delayed clinical management and reducing dengue-related mortality. Methods　Clinical and laboratory examination data of 831 patients admitted to Ruili People's Hospital of Yunnan Province during 2019-2023 were retrospectively collected. The dataset was divided into a training set and a validation set in a 7∶3 ratio. Statistical description and univariate analysis were performed on the training set, with LASSO regression employed to screen variables, followed by logistic regression to develop a risk prediction model for severe dengue. Model performance was validated using ROC curves on both the training set and validation set. Results　A total of 831 dengue patients were included in the study, with a mean age of (44.20±15.02) years. Among them, 52.59% were male and 5.42% were Myanmar nationality. In total, 122 cases (14.68%) exhibited severe dengue or dengue with warning signs, predominantly female (58.20%). LASSO regression was used in the training set to screen 11 variables related to the risk of severe dengue and dengue with warning signs: Age, dizziness, vomiting, prothrombin time, partial activated thromboplastin time, hematocrit, platelet, monocyte percentage, absolute value of monocytes, hemoglobin, C-reactive protein (λmin= 0.011 59); Logistic regression identified statistically significant variables for the risk model of severe dengue and dengue with warning signs as follows: age [OR=1.034 (95%CI: 1.016-1.053)], red blood cells deposited [OR=1.258 (95%CI: 1.143-1.519)], platelet [OR=0.991 (95%CI: 0.985-0.997)], hemoglobin (OR=0.919 (95%CI: 0.873-0.950)], C-reactive protein [OR=1.019 (95%CI:1.004-1.034)]. The model achieved an AUC of 0.894 (95%CI: 0.796-0.867) in the training set and 0.862 (95%CI: 0.709-0.827) in the validation set. At a cut-off threshold of 0.197, sensitivity and specificity were 0.850 and 0.743, respectively. Conclusion　This study established a LASSO-logistic regression model, which can predict the risk of severe dengue and dengue with warning signs. The model enhances the capability of hospitals to prevent and manage severe dengue and provides valuable guidance for clinical decision-making.

BACKGROUND: Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style. METHODS: We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases. RESULTS: The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals. CONCLUSIONS The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans ; Colonoscopy/methods* ; Deep Learning ; Decision Support Systems, Clinical ; Female ; Male

Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, the surgical risk and unclear mechanism hamper the clinical application. Numerous evidences support macrophages as the key immune cells during bone remodeling. Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1^CreERT2; R26^GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, and western blot determined the significantly enhanced expression of binding immunoglobulin protein (BiP) and emphasized the activation of sensor activating transcription factor 6 (ATF6) in macrophages. Then, we verified that macrophage specific ATF6 deletion (ATF6^f/f; CX3CR1^CreERT2 mice) decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy. In contrast, macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement. In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6. At the mechanism level, RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfα promotor and augmenting its transcription. Additionally, molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element (ERSE). Taken together, ATF6 may aggravate orthodontic bone remodeling by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
Animals ; Mice ; Macrophages/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Tooth Movement Techniques/methods* ; Activating Transcription Factor 6/metabolism* ; Bone Remodeling ; Flow Cytometry ; Blotting, Western

Objective To investigate whether there are sex differences in inflammatory bowel disease(IBD)among the offspring of mice with IBD.Methods BALB/c female mice were randomly divided into Na?ve and DSS groups.The mice in the Na?ve group drank autoclaved water freely,and the DSS group freely drank 2％dextran sodium sulfate(DSS)for 7 days before it was replaced with autoclaved water for 10 days.A total of 3～4 cycles were applied,and the IBD female mice were paired with healthy male mice in cages.When the pups were 8 weeks old,they were divided into the Con group and IBD group.The Con group drank autoclaved water freely for 7 days,and the IBD group drank 3％DSS for 7 days.During the modeling period,disease activity index was scored by monitoring body weight,fecal consistency,and the presence of blood in stool every day.Pathological sections were taken to observe changes in goblet cells and the mucus layer of colon tissues.The concentrations of interleukin(IL)-6,IL-1β,IL-33,and IL-10 in the colon were detected by enzyme-linked immunosorbent assay.Real-time quantitative PCR was used to determine the mRNA expression levels of tight-junction proteins and MUC-2 in the colon.Results Compared with female IBD mice,male IBD mice had higher DAI scores,significantly shorter colons,larger amounts of inflammatory infiltrate,more crypt abnormalities,and a higher absence of goblet cells in the colon;their relative mRNA expression of occludin mRNA was significantly reduced,levels of IL-6 and IL-33 were significantly increased,and level of IL-10 was significantly decreased.Conclusions The symptoms of colitis in the offspring of IBD mice were more severe in male than in female mice,a result that was mainly attributed to the more severely impaired intestinal epithelial barrier function in males.

Unique factors in the space environment can cause dysbiosis of astronauts' gut microbiota and its metabolites, which may exert systematic physiological effects on human body. Recent progress regarding the effect of space flight/simulated space environment (SF/SPE) on the composition of gut microbiota and its metabolites was reviewed in this paper. SF/SPE may cause the increase of invasive pathogenic bacteria and the decrease of beneficial bacteria, aggravating intestinal inflammation and increasing intestinal permeability. SF/SPE may also cause the decrease of beneficial metabolites or the increase of harmful metabolites of gut microbiota, leading to metabolism disorder in vivo, or inducing damage of other systems, thus not beneficial to the health and working efficiency of astronauts. Summarizing the effects of SF/SPE on gut microbiota may provide scientific basis for further researches in this field and the on-orbit health protection of astronauts.
Humans ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology* ; Bacteria/metabolism*

Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE^-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg^-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.
Animals ; Mice ; Atherosclerosis/drug therapy* ; Diet, High-Fat ; Endothelial Cells ; Inflammation/drug therapy* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Reactive Oxygen Species

Objective:To retrospectively analyze clinical efficacy and safety of omalizumab in the treatment of chronic urticaria (CU) in southern Zhejiang, China.Methods:A retrospective observational study was conducted on CU patients who received omalizumab treatment at the First Affiliated Hospital of Wenzhou Medical University from January 1st, 2018 to August 1st, 2021. Through the outpatient follow-up visits, the disease activity, condition control, and quality of life were evaluated using the 7-day urticaria activity score (UAS7) , urticaria control test (UCT) , and dermatology life quality index (DLQI) . In addition, changes in disease condition, recurrence after withdrawal, and adverse events were assessed. Independent-sample t test was used for intergroup comparisons of normally distributed measurement data, Wilcoxon signed-rank sum test or Kruskal-Wallis H test was used for comparisons of non-normally distributed measurement data, and chi-square test or Fisher′s exact test was used for comparisons of enumeration data. Results:A total of 252 CU patients with poor response to antihistamines were included, with a baseline UCT score of 5.0 ± 2.4 points, a UAS7 score of 25.6 ± 6.2 points, and a DLQI score of 17.5 ± 4.7 points; among them, 204 (81.0%) were treated with omalizumab at an initial dose of 300 mg, and 48 (19.0%) with omalizumab at an initial dose of 150 mg. At the end points (12.0 ± 1.4 months after the start of treatment) , an overall control rate of 90.3% (224/248) was achieved after the omalizumab treatment; concretely, 137 (55.2%) patients achieved complete control (UCT = 16 points) , 87 (35.1%) achieved partial control (12 points ≤ UCT < 16 points) , and 24 (9.7%) showed no response (UCT < 12 points) , while 10 with partial response shifted to complete control after dose increase. During the treatment period, recurrence occurred in 50 patients (36.5%) , of whom 32 patients opted for retreatment with omalizumab, and then 30 (93.8%) achieved partial or complete control. Adverse events were reported in 8 patients (3.2%) , and all were mild or moderate.Conclusion:Omalizumab was effective in the real-world treatment of CU, and could improve patients′ quality of life, with a favorable safety profile.

Objective:To investigate the role of hydrogen-rich salt water in improving depression-like symptoms and its possible molecular mechanism in rats.Methods:The experiment was divided into two stages. In the first stage, 35 healthy male SD rats were randomly divided into control group, model group, high-dose group, medium-dose group, and low-dose group ( n=7); rats in the control group and model group were gavaged with 8 mL/kg normal saline per d, and rats in the high-dose group, medium-dose group, and low-dose group were fed with 8 mL/kg hydrogen-rich saline water (containing 2, 1, and 0.5 ppm hydrogen) per d; except for the control group, the other groups were depressed with chronic unpredictable mild stimulation (CUMS) for 4 weeks. In the second stage, 30 healthy male SD rats were randomly divided into hydrogen water group, hydrogen water+fluoxetine group, and nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition group ( n=10); optimal hydrogen concentration (0.8 ppm) hydrogen-rich saline water (8 mL/kg) per d was given to rats of these 3 groups by gavage; fluoxetine (5 mg/kg) by gavage was given to the hydrogen-water+fluoxetine group, and all-transretinoic acid (10 mg/kg) by gavage was given to the Nrf2 inhibition group; CUMS was given for 4 weeks in these 3 groups. Rats were weighed at fixed times at each weekend. Four weeks after intervention, the total distance and average speed of rats in each group were determined by open field test. After open field test, blood was collected from the orbital veins from all rats; serum superoxidase dismutase (SOD) and malondialdehyde (MDA) contents were determined by ELISA. The expressions of brain-derived neurotrophic factor (BDNF), heme oxygenase-1 (HO-1), Nrf2, and phosphorylated Nrf2 (p-Nrf2) in the hippocampal CA3 region were detected by Western blotting. Results:(1) In the first stage, after 3 and 4 weeks of intervention, as compared with the model group, the body weight of the rats in the high-dose group, medium-dose group, and low-dose group increased significantly ( P<0.05). As compared with the model group, the medium-dose group, and low-dose group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, significantly increased BDNF and HO-1 expressions and decreased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). (2) In the second stage, after 3 and 4 weeks of intervention, as compared with the Nrf2 inhibition group, the body weight of the hydrogen water group and hydrogen water+fluoxetine group increased significantly ( P<0.05). As compared with the Nrf2 inhibition group, the hydrogen water group and hydrogen water+fluoxetine group had significantly increased total distance and average speed, significantly increased serum SOD content, significantly decreased serum MDA content, statistically increased BNDF and HO-1 expressions in the CA3 region of the hippocampus, and the hydrogen water+fluoxetine group had significantly increased Nrf2 and p-Nrf2 expressions in the CA3 region of the hippocampus ( P<0.05). As compared with the hydrogen water group, the hydrogen water+fluoxetine group had significantly increased BNDF and HO-1 expressions and increased p-Nrf2 expression in the CA3 region of the hippocampus ( P<0.05). Conclusion:Hydrogen-rich salt water can increase the serum SOD and reduce the serum MDA, increase the BDNF and HO-1 protein expressions in the hippocampal areas of depressed rats, thereby improving the depression-like symptoms; the synergistic effect of hydrogen-rich saline water and fluoxetine on anti-depression may be related to antioxidant effect of Nrf2 signaling.

Objective To investigate the effect of Kenpaullone on memory dysfunction in Alzheimer's disease (AD) model rats and its possible mechanism.Methods Twenty healthy male SD rats were divided into control group,model group,low dose group and high-dose group by random number table method (n=5).The rats in the control group did not receive any treatment;2 μL 0.5 mol/L wortmannin was injected into the hippocampal area of rats in the later three groups via stereotaxic method;The rats in the high-dose and low-dose groups were further injected with 5 μL 1 mmol/L and 5 μL 0.5 mmol/L Kenpaullone 24 h after wortmannin injection.Three weeks after Kenpaullone injection,the memory functions of rats in each group were measured by water maze.The expressions of cyclin-dependent kinase-5 (CDK5)/p25,glycogen synthase kinase-3β (GSK3β) and phosphorylated tau (p-tau) in the hippocampal CA3 regions were determined by immunohistochemistry.Synapsin Ⅰ expression was detected by Western blotting.Results (1) In the water maze experiment:as compared with those in the model group,the incubation periods of rats in the high-dose and low-dose groups were significantly shortened (P＜0.05);as compared with those in the model group and the low-dose group,the times of crossing the platform and the retention time in the high-dose group were significantly increased (P＜0.05).(2) In immunohistochemical staining,as compared with the model group,the high-dose group had significantly decreased CDK5,GSK-3β,and p-tau expressions (P＜0.05).(3) Western blotting indicated that as compared with that in the model group,synapasin Ⅰ expression was significantly increased in the high-dose group (P＜0.05).Conclusion Kenpaullone can decrease the GSK-3β,CDK5/p25 and p-tau protein expressions and increase synapsin Ⅰ protein expression in the hippocampus CA3 region,and improve cognitive dysfunction of the rats.

Objective To explore the effects of two different methods on the blood glucose variability (BGV) of patients with traumatic brain injury (TBI) who had performed the surgery.Methods A total of 100 patients with TBI after the surgery, who were admitted at intensive care unit ( ICU) from June 2013 to July 2014, were randomly assigned to the observation group ( n=50) and the control group ( n=50) . Patients in the control group received the routine treatment to adjust the BVG. Patients in the observation group received the modified Leuven′s adjustment processes. Blood glucose was continuously monitored in 5 days and all the data include mean blood glucose, incidence of hypoglycemia (level of blood glucose≤3.2 mmol/L), blood glucose standard deviation (SD), mean amplitude of glycemic excursions (MAGE) and glucose lability index (GLI) were performed statistical analysis. Results Mean blood glucose was stable in 5 days after operation in two groups (P>0.05). The blood glucose SD, MAGE and GLI in the observation group among the first 2 days [1st day:(4.7±1.2), (0.86±0.41), (255.9±213.7);2nd day:(4.0±1.7), (0.63±0.38), (202.7±163.5)] was higher than the control group [1st day:(1.1±0.68), (0.51±0.25), (112.7±92.8); 2nd day: (1.2±0.44), (0.41±0.17), (93.1±72.7)], and the difference was statistically significant (P<0.05). In the last 3 days, these data between two groups all fallen and the difference was insignificant ( P>0. 05 ) . The incidence of hypoglycemia in the observation group was lower than that of the control group in the 1st day ( P<0.05) . In the last 4 days, the data in two groups fell (P>0.05).Conclusions The modified Leuven′s adjustment processes has characteristics of early adjustment, accessible and operate simply. It is better than the routine adjustment processes in the BGV control at the early stage.