ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang （DCQD） on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins ［claudin-1， tumor necrosis factor （TNF）-α， interleukin （IL）-6， endogenous antimicrobial peptide mCRAMP， Toll-like receptor 4 （TLR4）， and myeloid differentiation primary response gene 88 （MyD88）］ in sepsis. Fifty C57BL/6 mice were randomized into sham， model， low- and high-dose （4 g∙kg^-1 and 8 g∙kg^-1） DCQD， and ulinastatin groups （n=10）. Before， during， and after the day of modeling surgery， each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay （ELISA） was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue， which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP， TLR4， and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction， on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force， hydrogen bonding， and other conjugated systems. The results of animal experiments showed that compared with the model group， low- or high-dose DCQD lowered the D-lactic acid level in the serum （P<0.01）， alleviated damage to the ileal tissue and mucosal edema， protected the small intestine villus integrity， reduced inflammatory cell infiltration， promoted the expression of claudin-1 （P<0.01）， lowered the IL-6 level （P<0.01）， up-regulated the mRNA and protein levels of mCRAMP （P<0.01）， and down-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.01） in the ileal tissue. In addition， high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue （P<0.01）， and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue （P<0.05）. ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation， repair intestinal mucosal damage， improve the tight junction protein level， and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.

Acute myocardial infarction (AMI) is a prevalent and serious cardiovascular disease characterized by a complex inflammatory response and myocardial tissue remodeling. The early inflammatory response plays a key role in the aftermath of AMI, promoting myocardial injury and repair. At the same time, ventricular remodeling, as a physiological process after AMI, involves myocardial hypertrophy, fibrosis, dilation, and remodeling, which has a profound impact on cardiac function and prognosis. Therefore, it is of great significance to understand the mechanism of action of early inflammation and ventricular remodeling after AMI. In this paper, the mechanism of early inflammation and ventricular remodeling after AMI was systematically reviewed, focusing on the dynamic changes of inflammatory mediators after AMI and the correlation between ventricular remodeling and prognosis, hoping to provide guidance and reference for the prevention, treatment, and prognosis of AMI.

Objective:To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes.Methods:A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results:Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR=4.58,95% CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR=0.90, 95% CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL ( OR=11.58, 95% CI 2.10-63.93, P=0.005) and preterm birth ( OR=4.98, 95% CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions:SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds. Photothermal therapy (PTT) emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat. However, the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues. Besides, the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation. Herein, we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds. Gelatin was used as inner layer hydrogel to reserve lysozyme (LZM) loaded mesoporous polydopamine (MPDA) (MPDA-LZM) nanoparticles, which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles. MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability, could deeply penetrate and destroy biofilms. In addition, the outer layer hydrogel consisted of gelatin methacryloyl (GelMA) and epidermal growth factor (EGF) promoted wound healing and tissue regeneration. It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo. Overall, the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds.

To further enhance the immune effect of the foot-and-mouth disease (FMD) virus-like particles (VLPs) vaccine, this study prepared FMDV VLPs-zeolitic imidazolate (framework-8, ZIF-8) complexes with different particle sizes. We used a biomimetic mineralization method with Zn²⁺ and 2-methylimidazole in different concentration ratios to investigate the effect of size on the immunization effect. The results showed that FMDV VLPs-ZIF-8 with three different sizes were successfully prepared, with an approximate size of 70 nm, 100 nm, and 1 000 nm, respectively. Cytotoxicity and animal toxicity tests showed that all three complexes exhibited excellent biological safety. Immunization tests in mice showed that all three complexes enhanced the titers of neutralizing and specific antibodies, and their immune effects improved as the size of the complexes decreased. This study showed that ZIF-8 encapsulation of FMDV VLPs significantly enhanced their immunogenic effect in a size-dependent manner.
Animals ; Mice ; Foot-and-Mouth Disease/prevention & control* ; Foot-and-Mouth Disease Virus ; Antibodies, Neutralizing ; Immunity, Humoral ; Immunization ; Vaccines, Virus-Like Particle ; Antibodies, Viral ; Viral Vaccines

Objective    To establish a machine learning model based on computed tomography (CT) radiomics for preoperatively predicting invasive degree of lung ground-glass nodules (GGNs). Methods    We retrospectively analyzed the clinical data of GGNs patients whose solid component less than 3 cm in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital from March 2021 to July 2021 and the First Hospital of Lanzhou University from January 2019 to May 2022. The lesions were divided into pre-invasiveness and invasiveness according to postoperative pathological results, and the patients were randomly divided into a training set and a test set in a ratio of 7∶3. Radiomic features (1 317) were extracted from CT images of each patient, the max-relevance and min-redundancy (mRMR) was used to screen the top 100 features with the most relevant categories, least absolute shrinkage and selection operator (LASSO) was used to select radiomic features, and the support vector machine (SVM) classifier was used to establish the prediction model. We calculated the area under the curve (AUC), sensitivity, specificity, accuracy, negative predictive value, positive predictive value to evaluate the performance of the model, drawing calibration and decision curves of the prediction model to evaluate the accuracy and clinical benefit of the model, analyzed the performance in the training set and subgroups with different nodule diameters, and compared the prediction performance of this model with Mayo and Brock models. Two primary thoracic surgeons were required to evaluate the invasiveness of GGNs to investigate the clinical utility of the mode. Results    A total of 400 patients were divided into the training set (n=280) and the test set (n=120) according to the admission criteria. There were 267 females and 133 males with an ……

Objective:To compare safety and efficacy of one-stage laparoscopic common bile duct exploration plus laparoscopic cholecystectomy (LCBDE+ LC) with endoscopic retrodrade cholangiopancreatography plus laparoscopic cholecystectomy (ERCP+ LC) in elderly patients with concomitant gallbladder and common bile duct (CBD) stones.Methods:This is a two-center retrospective study with clinical data on 492 patients aged over 80 years diagnosed with concomitant gallbladder and CBD stones treated between January, 2014 and December, 2020 at The First Affiliated Hospital of Wenzhou Medical University and Quzhou Hospital Affiliated to Wenzhou Medical University. There were 254 males and 238 females, aged (83.9±3.0) years. These patients were divided into two groups based on their operative methods: the one-stage group (LCBDE+ LC, n=186) and the two-stage group (ERCP+ LC, n=306). Differences in surgery, stones and hospitalization costs were compared between the two groups. Results:When compared with the ERCP+ LC group, the LCBDE+ LC group had significantly higher incidences of previous gastrectomy [21.5%(40/186) vs 4.2%(13/306)], multiple stones [77.4%(144/186) vs 49.3%(151/306)], larger stone diameter [13.7(6.4, 18.6)mm vs 10.9(5.7, 16.1) mm], and increased hospitalization expenditure [(2.37±0.31) Wanyuan vs (3.26±0.44) Wanyuan] (all P<0.05). However, the rates of residual stone [2.7%(5/186) vs 1.3%(4/306)], stone recurrence [2.2%(4/186) vs 5.2%(16/306)], postoperatively overall complications [3.2%(6/186) vs 1.3%(4/306)], and total hospital stay [(10.7±6.2) d vs (11.3±5.4) d] were not significantly different between the two groups (all P>0.05). Conclusions:Allowing for the similar safety and effectiveness, and lower hospitalization expenditure, LCBDE+ LC was a preferred choice for patients aged over 80 year, especially in patients who had previous gastrectomy, multiple large CBD stones, or who could not accept endoscopic procedures for treatment of CBD stones.

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

Dichlorvos poisoning can cause muscarinic (M) -like symptoms, nicotinoid (N) -like symptoms and central nervous system manifestations. When severe poisoning is combined with refractory shock, the mortality rate exceeds 60%. At present, there are more and more studies on ECMO for poisoning, but there is no report on ECMO for treating refractory hypotension caused by dichlorvos poisoning. We analyzed 3 successful cases of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the treatment of refractory shock caused by acute severe dichlorvos poisoning to explore the effectiveness of VA-ECMO in patients with severe poisoning.

Objective:To use the resting state functional network connectivity (FNC) method based on independent component analysis (ICA) to analyze the characteristics of FNC changes in patients with basal ganglia aphasia (BGA) after stroke, and to explore its occurrence and recovery mechanism under the intervention of acupuncture combined with language rehabilitation training.Methods:Using a prospective observational research method, 16 right-handed BGA patients who were treated at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from July 2021 to December 2022, as well as 14 healthy subjects matched in age, gender, education level, and handedness, were included. The resting state functional magnetic resonance imaging, demographic information, and Western Aphasia Examination data of healthy subjects and BGA patients before and after intervention were collected. The GIFT toolbox based on MATLAB platform was applied for ICA and resting state brain network FNC analysis. The FNC differences between BGA patients and healthy subjects were compared horizontally, and the FNC changes in BGA patients before and after intervention were compared vertically.Results:Compared with healthy subjects, post-stroke BGA patients showed decreased connectivity between the basal ganglia network, default network, and visual network before intervention, while increased connectivity between the auditory network, right frontoparietal network, and anterior cuneiform network; After the intervention of acupuncture combined with language rehabilitation training, the connectivity between the basal ganglia network, visual network, and anterior cuneiform network decreased, while the connectivity between the anterior convex network and bilateral frontoparietal network decreased, while the connectivity between the default network, auditory network, right frontoparietal network, and visual network increased. The BGA patient group showed enhanced connectivity between the basal ganglia network and the left frontoparietal network before and after intervention.Conclusions:The FNC changes between the basal ganglia network and other brain networks are key to reflecting the mechanism of BGA occurrence and language function recovery. Acupuncture combined with language rehabilitation training may improve language function by enhancing the connectivity between the basal ganglia network and the left frontoparietal network, and the redistribution of attention resources may also be one of the reasons for promoting language function recovery in BGA patients.