Diffuse infiltrating retinoblastoma is an extremely rare form of retinoblastoma which is characterized by its atypical growth pattern. This unusual presentation adds complexity to the diagnostic process. The purpose of this paper is to report a rare presentation of diffuse infiltrating retinoblastoma presenting after an ocular trauma. We described a 7-year-old Filipino boy presenting with total hyphema following an ocular trauma. Comprehensive ophthalmologic clinical and diagnostic evaluations were performed including visual acuity, slitlamp biomicroscopy, ocular ultrasound, neuroimaging, and histopathology post enucleation to determine diagnosis. The misleading, atypical presentation of diffuse infiltrating retinoblastoma may delay diagnosis. While this dilemma is expected in these scenarios, it should be remembered that timing of diagnosis in retinoblastoma is crucial, as this also equates to optimal management. One should remain vigilant for these uncommon presentations especially in the setting of any intraocular inflammation in children.

Human ; Male ; Child: 6-12 Yrs Old ; Wounds And Injuries ; Visual Acuity ; Retinoblastoma ; Research Report ; Neuroimaging ; Inflammation ; Hyphema ; Contusions

BACKGROUND

Perimyocarditis due to inflammation of the pericardium and myocardium results in myocellular damage. Myocarditis, or myocardial inflammation, occurs after cardiac injury. Gallbladder edema, in the absence of cholecystitis, may occur in numerous conditions including cardiac inflammation.

CASE PRESENTATION

A 28-year-old previously healthy female presented with chest pain, orthopnea, exertional dyspnea and a history of fever. She also reported intermittent right upper quadrant pain. Physical exam revealed a pericardial friction rub. Electrocardiogram (ECG) showed sinus rhythm with nonspecific ST-T changes; troponin I was elevated. Echocardiography demonstrated segmental wall motion abnormalities, pericardial thickening and preserved systolic function. Initially managed as acute coronary syndrome, she was later diagnosed with perimyocarditis. On the second hospital day, she developed recurrence of right upper quadrant abdominal pain. Abdominal ultrasound revealed gallbladder edema with pericholecystic fluid, but no stones. Liver enzymes were elevated. Acalculous cholecystitis was considered and cholecystostomy offered instead due to aspirin therapy. However, repeat imaging showed resolution of cardiac and gallbladder findings, and surgery was deferred. Cardiac MRI postdischarge was unremarkable.

CONCLUSION

Perimyocarditis may present with gallbladder edema mimicking acalculous cholecystitis, potentially leading to unnecessary surgical intervention. This case emphasizes the importance of considering cardiac etiologies in atypical abdominal presentations.

Human ; Female ; Adult: 25-44 Yrs Old ; Acalculous Cholecystitis ; Research Report ; Pericardium ; Myocardium ; Myocarditis ; Inflammation

BACKGROUND AND OBJECTIVES

A mounting evidence links dysregulated immune response to cases of fatal pneumonia seen in COVID-19 infection. We aimed to validate the COVID-19-associated Hyperinflammatory Syndrome (cHIS) score, a novel clinical tool devised to identify those at risk for adverse outcomes, in a local population and investigate the relationship of cHIS score taken at admission and the risk of mortality and the need of mechanical ventilation.

METHODS

This retrospective cohort study analyzed the sociodemographic, clinical, and laboratory data of 1,881 COVID-19 patients admitted at a tertiary hospital in Davao City, Philippines from January to December 2021. We calculated the cHIS score, composed of six clinical and laboratory criteria from admission, and used multivariate logistic regression to determine the risk of mortality and need of mechanical ventilation.

RESULTS

The cHIS score taken at admission, regardless of cut-off value, was a significant predictor of mortality (OR 0.979 [99% CI 0.894-1.064]) and need of mechanical ventilation (OR 0.586 [99% CI 0.4975-0.6745]). Using the Youden Index, a cut-off cHIS score of 3 or more was a better predictor of mortality (sensitivity, 88.59%; specificity, 71.72%), and a cut-off score of 2 or more was a better predictor of need of mechanical ventilation (sensitivity, 84.02%; specificity, 70.82%) than other cutoff cHIS scores.

CONCLUSION

Among COVID-19 patients, the cHIS score at admission correlated with the risk of mortality and the need of mechanical ventilation. Cutoff scores of 3 and 2 had the optimal sensitivities and specificities to predict the risk of mortality and the need of mechanical ventilation, respectively.

Human ; Covid-19 ; Inflammation ; Mortality ; Mechanical Ventilation ; Respiration, Artificial ; Cytokine Storm ; Cytokine Release Syndrome

Cardioembolic stroke is a special type of ischemic stroke caused by cardiac diseases， and its development is closely associated with the structural and functional abnormalities of the heart. The pathophysiological mechanisms of this type of stroke are complex. It is often induced by thrombosis due to cardiac diseases， followed by thrombus detachment and entry into cerebral vessels， leading to ischemic injury and subsequent cascade reactions. Inflammatory response plays a crucial role in the development and progression of cardioembolic stroke， being involved in processes ranging from thrombosis to acute-phase brain injury after embolism， short-term neurological recovery， and long-term prognosis prediction， and can also be used as a biomarker and diagnostic factor. This article summarizes the mechanism by which inflammation contributes to the development and progression of cardioembolic stroke， as well as the current research advances in the etiology of cardioembolic stroke， the recovery of neurological function after stroke， and personalized treatment strategies.
Inflammation

Aging involves the accumulation of various forms of molecular and cellular damage over time. Key features of aging, such as mitochondrial dysfunction, dysbiosis, and oxidative stress, are closely linked and largely driven by inflammation. This study examines the role of succinate, a key metabolite produced and utilized by cells of both host and microbes, and its receptor, succinate receptor 1 (SUCNR1), in age-related oral dysbiosis and inflammation. We examined young and aged wild-type (WT) and SUCNR1 knockout (KO) mice for this analysis. Our findings revealed significant aging-associated alveolar bone loss and succinate elevation in aged WT mice, along with notable changes in the oral microbiome. Conversely, aged KO mice showed reduced bone loss, lower succinate levels, less inflammation, and better-maintained microbial function. These results suggest that SUCNR1 is crucial in influencing aging-related succinate elevation, oral dysbiosis, and inflammation. Analysis of gene families and pathways in the oral microbiome demonstrated distinct aging-related changes between WT and KO mice, with the functional potential being preserved in the KO-aged group. This study underscores the importance of succinate elevation and signaling through SUCNR1 in regulating inflammation, alveolar bone loss, and shifts in the oral microbiome, offering potential targets for therapeutic interventions in age-related oral health issues.
Animals ; Dysbiosis/metabolism* ; Mice ; Succinic Acid/metabolism* ; Mice, Knockout ; Receptors, G-Protein-Coupled/metabolism* ; Inflammation/metabolism* ; Aging ; Alveolar Bone Loss/metabolism* ; Mouth/microbiology* ; Mice, Inbred C57BL ; Male ; Microbiota

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Activating transcription factor 5 (ATF5) is a member of the activating transcription factor/cyclic adenosine monophosphate response element binding protein (ATF/CREB) family. As a stress-induced transcription factor, ATF5 plays a crucial role in cellular inflammatory stress responses. Under cellular inflammatory stress conditions, ATF5 maintains cell homeostasis and survival by regulating key genes in the mitochondrial unfolded protein response (UPR^mt) and endoplasmic reticulum stress (ERS). As a key regulator in UPR^mt, ATF5 senses mitochondrial stress and translocate to the nucleus to activate the transcription of UPR^mt-related genes, thereby promoting mitochondrial function recovery. Meanwhile, in ERS, ATF5 maintains endoplasmic reticulum homeostasis by regulating the expression of genes related to protein folding, degradation, and apoptosis, determining cell survival or death. ATF5 plays a vital role in various cellular inflammatory stress responses. In infectious inflammation, ATF5 plays an important role in alleviating neuroinflammation and maintaining intestinal barrier function by regulating UPR^mt. In inflammation related to degenerative diseases, ATF5 improves intervertebral disc degeneration and delays the progression of osteoarthritis by regulating UPR^mt. In metabolic inflammation such as diabetes and obesity, ATF5 regulates UPR^mt and ERS to maintain the function of pancreatic β-cells, controlling their survival or inducing apoptosis, thus influencing the progression of diabetes. ATF5 protects mitochondria in the kidneys, adipose tissue, and pancreas, slows the progression of diabetic nephropathy, and improves insulin sensitivity. Furthermore, in immune-related inflammation, ATF5 alleviates glomerulonephritis and promotes tissue repair by enhancing immune tolerance in dendritic cells. In summary, ATF5, as a key regulator in cellular inflammatory stress responses, maintains cell homeostasis through regulating UPR^mt and ERS and determines cell fate. Its critical regulatory role in cellular inflammatory stress responses makes ATF5 a potential clinical therapeutic target. This article summarizes the structural features and translational regulatory mechanisms of ATF5, focusing on its role in cellular inflammatory stress responses, particularly its regulatory mechanisms in UPR^mt and ERS, aiming to provide a theoretical basis for understanding ATF5's role in cell and organ protection and to offer new insights into the treatment of related inflammatory diseases.
Humans ; Endoplasmic Reticulum Stress ; Inflammation/metabolism* ; Activating Transcription Factors/metabolism* ; Unfolded Protein Response ; Mitochondria/metabolism* ; Apoptosis ; Animals

OBJECTIVE: To investigate the interaction between α-amylase (α-AMS) and inflammatory response in patients with ventilator-associated pneumonia (VAP) and their predictive value for prognosis. METHODS: A prospective cohort study was conducted. Patients with mechanical ventilation who were treated in the intensive care unit (ICU) of the Second Hospital of Hebei Medical University from June 2020 to June 2023 were enrolled, and the patients were divided into VAP group and non-VAP group according to whether VAP occurred. VAP patients were stratified into mild [acute physiology and chronic health evaluation II (APACHE II) < 10 scores], moderate (APACHE II were 10-20 scores), and severe (APACHE II > 20 scores) groups based on the APACHE II. All patients were followed up for 28 days. In addition, healthy subjects who underwent health examination in our hospital at the same time were selected as the healthy control group. Baseline data including gender, age, mechanical ventilation mode, mechanical ventilation time, underlying diseases, drug use, and laboratory test indicators were collected. The serum levels of α-AMS, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and other inflammatory factors were analyzed and compared. Pearson correlation analysis was performed to analyze the correlation between serum α-AMS and inflammatory factors. Logistic regression was used to analyze the influencing factors of poor prognosis in patients with VAP. The receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive value of α-AMS on the poor prognosis of patients with VAP. RESULTS: A total of 100 mechanically ventilated patients were enrolled, including 60 cases in the VAP group and 40 cases in the non-VAP group. Among the patients with VAP, there were 24 cases in the mild group, 20 cases in the moderate group, and 16 cases in the severe group. A total of 44 patients survived at 28 days, while 16 died. Additionally, 100 healthy individuals were included as the healthy control group. Serum levels of α-AMS, IL-6, TNF-α and CRP in the VAP group were significantly higher than those in the non-VAP group and the healthy control group, while the levels of α-AMS, IL-6, TNF-α and CRP in the non-VAP group were significantly higher than those in the healthy control group. There were statistically significant differences in serum α-AMS, IL-6, TNF-α, CRP levels and APACHE II scores among VAP patients with different disease severities, and the levels of the above indicators in the severe group were significantly higher than those in the moderate group and mild group, and the levels of the above indicators in the moderate VAP group were significantly higher than those in the mild group. Pearson correlation analysis showed that serum α-AMS was positively correlated with IL-6, TNF-α, CRP, and APACHE II scores (r values were 0.404, 0.392 and 0.493, 0.493, all P < 0.01). Univariate analysis showed that age, mechanical ventilation, diabetes mellitus, ventilation time, ventilation position, prophylactic use of antimicrobial drugs, and serum α-AMS, IL-6, TNF-α, CRP, and APACHE II scores were correlated with the prognosis of VAP patients (all P < 0.05). Multivariate Logistic regression analysis identified age [odds ratio (OR) = 1.340, 95% confidence interval (95%CI) was 1.119-1.605], tracheostomy (OR = 3.050, 95%CI was 1.016-9.157), diabetes mellitus (OR = 1.379, 95%CI was 1.102-1.724), and ventilation time ≥ 7 days (OR = 2.557, 95%CI was 1.163-5.623) and serum α-AMS (OR = 1.428, 95%CI was 1.098-1.856), IL-6 (OR = 1.543, 95%CI was 1.005-2.371), TNF-α (OR = 2.228, 95%CI was 1.107-4.485), CRP (OR = 1.252, 95%CI was 1.131-1.387), APACHE II scores (OR = 1.422, 95%CI was 1.033-1.957) were independent influencing factors for the 28-day prognosis of patients with VAP (all P < 0.05). ROC curve analysis demonstrated that serum α-AMS, IL-6, TNF-α and CRP exhibited significant predictive performance on the prognosis of patients with VAP. The best cut-off value for α-AMS had a sensitivity of 81.3%, specificity of 75.0%, and an area under the ROC curve (AUC) of 0.791, which was significantly higher than those of inflammatory markers IL-6, TNF-α, and CRP (P < 0.05). The combined parameter diagnostic performance was significantly better than those of individual parameters (P < 0.05), with the highest diagnostic performance when combined, corresponding to an AUC of 0.868 (95%CI was 0.798-0.938), sensitivity of 87.5%, and specificity of 79.5%. CONCLUSIONS VAP in mechanically ventilated patients can lead to an increase in the levels of peripheral blood α-AMS and inflammatory factors, and there is an interaction between α-AMS and inflammatory markers in severe VAP patients. These markers are closely related to the severity of the disease and prognosis and have significant implications for predicting patient outcomes.
Humans ; Pneumonia, Ventilator-Associated/diagnosis* ; Prognosis ; Prospective Studies ; Respiration, Artificial ; alpha-Amylases/blood* ; Interleukin-6/blood* ; Male ; Female ; C-Reactive Protein/metabolism* ; APACHE ; Inflammation ; Middle Aged ; Intensive Care Units ; Tumor Necrosis Factor-alpha/blood* ; Aged

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*