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关键词： C-reactive protein   gastrointestinal cancer   interleukin 10   interleukin 6  

摘要： Gastrointestinal (GI) cancers represent a major global health burden, significantly impacts the digestive system. Recent research has focused on the relationship between interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) to deepen understanding of GI cancer-including esophageal, gastric, pancreatic, hepatobiliary, and colorectal cancers-pathogenesis and to enhance diagnostic and therapeutic strategies. Elevated levels of IL-6, IL-10, and CRP have been associated with advanced disease stages and poor prognosis, underscoring their potential utility as biomarkers for disease progression and outcome prediction. Moreover, these markers appear to modulate the sensitivity of GI cancer cells to chemotherapy, suggesting that their assessment in serum and tissue samples could aid therapeutic decision-making and predict treatment responses. In addition to their diagnostic and prognostic value, IL-6, IL-10, and CRP are being investigated as targets for preventive strategies. These findings highlight the potential role of anti-inflammatory interventions in chemoprevention. Overall, studying the interplay among IL-6, IL-10, and CRP has yielded valuable insights into the molecular mechanisms driving GI cancer development and progression. Continued research is essential to fully elucidate these complex interactions and to translate these findings into effective clinical applications for the management of GI malignancies.

关键词： Methicillin-resistant Staphylococcus aureus   Community-associated methicillin-resistant   Staphylococcus aureus   Social determinants of infectious disease   Bayesian hierarchical modeling   Counterfactual simulation   Mediation analysis   Incarceration   Health disparities   Racial disparities  

摘要： Purpose: Describe inequities in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections and identify social factors contributing to these disparities. Methods: We characterized census tract-level risk factors for CA-MRSA infections in the Cook County Health (CCH) catchment population in Cook County, IL from 2009 to 2022 using hierarchical Poisson regression models. We conducted mediation analyses to estimate a) the total risk attributable to and b) proportion of between-tract disparities in CA-MRSA accounted for by census tract-level inequities in risk factors. Results: CCH patients living in majority Black census tracts in Cook County had double the rate of CA-MRSA infections as compared to CCH patients living in majority white census tracts. Socio-economic indicators such as public transportation use and the presence of homeless shelters in a census tract were associated with CA-MRSA rates in multivariate analyses. However, jail admission rates explained the largest proportion of CA-MRSA burden (30 %) and racial inequities in CA-MRSA incidence (69 %). Discussion: High risks of MRSA infection and colonization have consistently been documented among incarcerated and recently incarcerated individuals. Our results suggest that incarceration may also drive infections among non-incarcerated individuals living in communities with high levels of indirect exposure to jails, especially in majority Black census tracts.

关键词： ADRs   adverse drug reactions   AEDs   antiepileptic drugs   AERD   aspirin-exacerbated respiratory disease   AGEP   acute generalized exanthematous pustulosis   BAT   basophil activation test   BLs   beta-lactam antibiotics   BSA   body surface area   CBZ   carbamazepine   CF   cystic fibrosis   CFTR   cystic fibrosis transmembrane conductance regulator   COX   cyclooxygenase   CR   cross-reactivity   DHR   drug hypersensitivity reactions   DIA   drug-induced anaphylaxis   DIES   drug-induced enterocolitis syndrome   DIHS   drug-indued hypersensitivity syndrome   DILI   drug-induced liver injury   DPT   drug provocation test   DRESS   drug reaction with eosinophilia and systemic symptoms   EBV   Epstein-Barr virus   EAACI   European Academy of Allergy and Clinical Immunology   ELISpot   Ennzyme-linked Immunosorbent Spot   ENDA   European Network on Drug Allergy   FPIES   food protein induced enterocolitis syndrome   GBCM   gadolinium-based contrast media   GVHD   graft-versus-host disease   HLA   human leukocyte antigen   HS   hypersensitivity   IDHRs   immediate drug hypersensitivity reactions   IDT   intradermal test   LEV   levetiracetam   LTG   lamotrigine   LTT   lymphocyte transformation test   MHC   major histocompatibility complex   MPE   maculopapular exanthema   MRGPRX2   mas-related G-protein-coupled receptor member X2   NECD   NSAID-exacerbated cutaneous disease   N-ERD   NSAID-exacerbated respiratory disease   NSAIDs   non-steroidal anti-inflammatory drugs   NIDHRs   non-immediate reactions   NIUAAA   NSAID -induced urticaria   angioedema   and anaphylaxis   NBLA   non-betalactam antibiotic   NMBA   neuromuscular blocking agents   NPV   negative predictive value   nsLTP   non-specific lipid transfer protein   PEG   polyethylene glycol   POH   peri-operative drug allergy   PS80   polysorbate 80   PI   pharmacological interaction   PT   patch test   RCM   Radio contract media   RDD   rapid drug desensitization   RIME   reactive infectious mucocutaneous eruption   sIgE   serum specific IgE   SCARs   severe cutaneous adverse reactions   STs   skin tests   SJS   Stevens-Johnson Syndrome   SPT   skin prick test   SSLR   serum sickness-like reactions   TCR   T-cell receptors   TEN   toxic epidermal necrolysis   TMP-SMX   trimethoprim-sulfamethoxazole  

摘要： Drug hypersensitivity reactions (DHRs) in children and adolescents are less common than in adults but can have serious consequences if mismanaged. Mislabeling children as drug-allergic due to incomplete diagnostic evaluations leads to unnecessary medication restrictions, increased healthcare costs, and suboptimal treatment choices. This Statement from the World Allergy Organization (WAO) provides evidence-based recommendations for evaluating and managing pediatric DHRs, emphasizing accurate diagnosis through in vivo and in vitro testing, risk stratification, and personalized approaches. Antibiotics, particularly b-lactams, and non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently implicated drugs, with non-immediate reactions, such as maculopapular exanthema, being the most common presentation. The document also addresses emerging concerns, including monoclonal antibody-induced anaphylaxis and drug-induced enterocolitis syndrome. It underscores the need for specialized care in allergy centers with expertise in pediatric populations and advocates for multidisciplinary programs to manage complex cases, such as chemotherapy hypersensitivity and perioperative drug allergy. By addressing diagnostic challenges and clinical uncertainties, this document aims to improve the management of DHRs in children, reduce mislabeling, and enhance patient outcomes worldwide.

关键词： berberine   pancreatic beta-cells   hormesis   p53 mediated apoptosis pathways   mitochondrial membrane potential  

摘要： Damage to pancreatic beta-cells serves as a critical pathological basis in the progression of diabetes. Berberine (BBR), an isoquinoline alkaloid, potentially protects pancreatic beta-cells, exerting hypoglycemic effects. However, the dose-response relationship and the specific protective mechanism are still unclear. Hormesis is a self-protective response triggered by mild stimuli and has been reported to determine the extent to which phytochemicals can combat diabetes. In this study, we found that BBR exhibited a typical hormetic effect in IL-1 beta-induced damage to pancreatic beta-cells, where low doses of BBR protect cells while high doses aggravate the damage. A model-based approach was used to describe dose-response relationships, as well as to detect and estimate hormetic effects. In addition, the regulatory effect of BBR in preventing apoptosis in pancreatic beta-cells was confirmed, and an appropriate dose of BBR stabilized the mitochondrial membrane potential and prevented DNA damage. Moreover, the results showed that the hormetic effect of BBR was closely related to p53 and apoptosis pathways. To further investigate the role of the p53-mediated apoptosis pathways, our study interfered with the p53 pathway, resulting in the attenuation of the hormetic effect of BBR. These results introduce the concept of hormesis to study the biphasic effects of berberine on damaged pancreatic beta-cells, while also exploring the relationship between the hormetic mechanism of BBR and the p53-mediated apoptosis pathway. These findings provide clues to explore the potential application of BBR in treating diabetes.

关键词： COVID-19   miRNA   IL-6   Diagnosis  

摘要： Background: The role of microRNAs (miRNAs) in viral diseases is well established. Due to the COVID-19 pandemic, this study analyzed the expression levels of miR200b-3p, miR34b-5p, miR203a-3p, and Let7g-5p in the blood samples of COVID-19 patients, along with the expression level of interleukin-6 (IL-6) as a biomarker. Objectives: The purpose of this study is to investigate the correlation between the expression levels of IL-6 and the mentioned miRNAs. Methods: The study included 60 COVID-19 patients confirmed by an infectious disease specialist and positive real-time PCR tests, hospitalized at Razi Hospital, Ahvaz. The control group consisted of thirty healthy people. COVID-19 disease was verified using oro-nasopharyngeal swab samples, and PBMC samples from patients were used to check the expression level of IL-6. Plasma samples were analyzed for the expression levels of miR200b-3p, miR34b-5p, miR203a-3p, and Let7g-5p. Results: All examined expression factors were markedly elevated in COVID-19 patients in comparison to the control group. Specifically, miR200b-3p (P < 0.00), Let7g-5p (P < 0.003), and miR203a-3p (P < 0.00) exhibited significantly higher levels in the infected group. MiR34b-5p (P < 0.02) also showed an increase, albeit to a lesser extent. Additionally, IL-6 expression was substantially higher in hospitalized patients. Positive correlations, though not statistically significant, were observed between miR200b-5p, miR203a-3p, miR34b-5p, and IL-6 expression. Conversely, a non-significant negative correlation was noted between Let7g and IL-6 in COVID-19 patients. Conclusions: This study establishes a relationship between the elevated expression of specific miRNAs (miR200b-3p, miR34b-5p, miR203a-3p, and Let7g-5p) and IL-6 in COVID-19 patients. The significant upregulation of these miRNAs, alongside increased IL-6 levels, underscores their potential role as biomarkers for COVID-19. These findings suggest that miRNA and IL-6 expression profiles could be instru

关键词： ginsenoside Rh2   interferon gamma   combination treatment   cancer   Rh2+IFN gamma signature genes (RISG)  

摘要： Interferon gamma (IFN gamma) can amplify immune cell-mediated anti-tumor immunity, as well as directly kill cancer cells. Ginsenoside Rh2 (Rh2), a bioactive compound in traditional Chinese medicine, exhibits anti-cancer effects such as inhibiting proliferation and metastasis. Our earlier research found that Rh2 combined with IFN gamma enhanced CXCL10 secretion in cancer cells. Here, we explored whether Rh2 and IFN gamma exerted more potent anti-cancer activity in vitro and in vivo, along with its mechanisms and clinical value. Our data showed that Rh2 in combination with IFN gamma resulted in a remarkably increased cytotoxicity in colorectal cancer cells including HT29, LoVo and T84 cell lines. Consistently, intratumoral injection with Rh2 plus IFN gamma further restricted the HT29 tumor growth in vivo, and importantly, it was demonstrated to be safe for mice. Meanwhile, the combo treatment activated the stimulator of interferon genes (STING) pathway in cancer cells, promoting the transcription of downstream type I interferon. RNA sequencing revealed a dramatically transcriptional alteration in cancer cells with combo treatment and indicated that Rh2 further augmented the activation of interferon signaling pathway, compared with the IFN gamma alone. Inhibition of janus kinase (JAK) by ruxolitinib could significantly rescue the cell death-triggered by the combo treatment. Then, a gene set named Rh2+IFN gamma signature genes (RISG) was defined, which contained top 20 significantly upregulated genes from the combo treatment. Patients who exhibited a favorable response to the immunotherapy had a higher expression of RISG in tumor compared with those who did not respond. And the high expression of RISG was correlated with better clinical outcome in patients with colorectal cancer (CRC) and skin cutaneous melanoma (SKCM). Herein, the combination of Rh2 with IFN gamma served as a promising strategy for cancer treatment, and its-derived RISG gene set also exhibited potentia