BACKGROUND:Antimicrobial resistance (AMR) is one of the most pressing global health problems, resulting from the misuse and overuse of antibiotics across various sectors, which has led to the emergence and spread of resistant microorganisms. AMR occurs when microorganisms no longer respond to antibiotics. In Italy alone, AMR is responsible for over 10,000 deaths each year, exceeding 40% of all AMR, attributable deaths in the EU/EEA. This alarming trend highlights the urgent need to preserve effective treatment options and to re-evaluate the role of well-established oral antibiotics with a favourable pharmacological and microbiological profile. SUMMARY:Ceftibuten is an oral third-generation cephalosporin with potent activity against many Gram-negative and some Gram-positive pathogens, including several Gram-negative pathogens. It is approved for the treatment of respiratory and urinary tract infections, both uncomplicated and complicated, in adults as well as in children. This review discusses clinical and pharmacological data supporting ceftibuten's efficacy, safety, pharmacokinetics, and microbiological spectrum. Moreover, the paper discusses its potential role in contemporary clinical practice, especially considering recent supply interruptions and increasing resistance patterns. KEY MESSAGES:Ceftibuten represents an oral treatment option for respiratory and urinary tract infections, particularly where resistance to other agents limits therapeutic choices. Its favourable pharmacokinetic profile, safety both in paediatric and adult populations, and efficacy against key resistant pathogens support use within approved indications. Finally, this antibiotic offers a favourable safety profile for both patients allergic to penicillin and cephalosporins, particularly third- and fourth-generation cephalosporins. Ensuring continued access to this antibiotic may contribute to appropriate management of infections in both community and hospital settings.
PURPOSE:This study aimed to elucidate the clinical attributes of vancomycin-induced linear IgA bullous dermatosis (LABD) to enhance diagnostic, therapeutic, and preventive approaches. METHODS:We conducted a retrospective analysis of vancomycin-induced LABD cases by reviewing the literature in Chinese and English databases up to July 31, 2025. RESULTS:A total of 104 patients were identified, with a median age of 70 years (range 29, 92). The median time to onset of LABD was 9 days (range 0.5, 20), with 80.7% of patients presenting symptoms within two weeks. The predominant clinical manifestations included blisters (87.1%), vesicles (41.3%), erythema (52.9%), and papules (19.2%), frequently accompanied by pruritus (18.3%). Mucosal involvement was noted in 26.9% of cases. Histopathological examination typically demonstrated inflammatory cell infiltration (79.8%). Direct immunofluorescence assays revealed linear IgA deposition along the basement membrane zone. After stopping vancomycin and receiving treatment, all patients exhibited significant improvement in their skin lesions. CONCLUSION:Clinicians should recognize LABD as a serious but infrequent adverse reaction to vancomycin. Increased vigilance is crucial during the initial two weeks of vancomycin treatment, especially in elderly patients over 60 years of age. LABD recovered completely after withdrawal of vancomycin and other treatments.
BACKGROUND:Research on the therapeutic benefits of psychedelics, particularly psilocybin, is becoming increasingly popular. Unfortunately, most psychedelic research overlooks the menstrual cycle as a biological variable, raising concerns about the safety and efficacy of findings for individuals who menstruate. Given the established effects of estradiol and progesterone (and metabolites) on serotonin receptor density and function, it is plausible that the subjective experience, efficacy, and side effect profile of psychedelics may vary significantly across the different phases of the menstrual cycle. Furthermore, the tolerance effects of psilocybin when taken on consecutive days are unknown. AIMS:The PsiMenis trial will comprises two sub-studies: PsiMen-M, which will assess the potential for the menstrual cycle to affect the response to low-dose psilocybin in healthy menstruating persons, and PsiMen-T, which will test for potential tolerance effects. METHODOLOGY:Psilocybin (5 mg) will be administered during different menstrual cycle phases in 21 healthy participants for PsiMen-M, and 12 for PsiMen-T. Effects on subjective experience, brain/cognitive function, and pharmacokinetics will be measured by the Drug Effects Questionnaire, exploratory task-based electroencephalography (EEG), and blood plasma sampling. Safety and any clinically significant modifications of psilocybin will be monitored by laboratory and vital signs tests. Tolerance to psilocybin will be assessed by administering the drug for three consecutive days. CONCLUSIONS/SIGNIFICANCE:This study will determine whether low-dose psilocybin effects vary across the menstrual cycle, addressing a key gap in psychedelic research. Findings may inform the development of serotonergic treatments for menstrual-cycle-related mood disorders and improve the design of future psychedelic trials by accounting for hormonal fluctuations.
INTRODUCTION:Myocardial ischemia-reperfusion (I/R) injury represents a key contributor to cardiac dysfunction and is associated with cardiomyocyte senescence. Dexmedetomidine (Dex) exhibits significant myocardial protective effects, but its molecular mechanisms in alleviating I/R-induced cardiomyocyte senescence remain unclear. METHODS:In this study, an I/R injury model was established in C57BL/6 mice. An in vitro injury model of H9C2 cardiomyocytes was constructed using the oxygen-glucose deprivation/reoxygenation method to evaluate the effects of Dex on senescence in myocardial tissue and cardiomyocytes. Histopathological changes were assessed using hematoxylin and eosin and Masson staining, while cellular senescence was evaluated through senescence-associated β-galactosidase staining. The levels of myocardial infarction-related factors were detected by ELISA. The expression of senescence-related markers (p27, p21, and p16) was measured by qRT-PCR and WB, and apoptosis was measured by TUNEL assay. Cell viability, proliferation, and oxidative stress (OS) levels were assessed by CCK-8, EDU, and DCFH-DA probes. RESULTS:In vivo and in vitro experiments showed that Dex alleviated I/R-induced myocardial histopathological damage, improved cardiomyocyte viability and proliferation, reduced OS, and suppressed cellular senescence. Mechanistic studies revealed that Dex inhibited activation of the NF-κB pathway by downregulating malate dehydrogenase 2 (MDH2), thereby attenuating cardiomyocyte senescence. CONCLUSION:Dex significantly mitigates I/R injury-driving cardiomyocyte senescence by blocking the MDH2/NF-κB signaling, providing a potential therapeutic strategy for ischemic heart disease.
Cardiovascular diseases (CVDs) represent a significant global public health challenge. Activation of the NLRP3 inflammasome contributes to CVD pathogenesis, while autophagy mitigates the condition by eliminating harmful metabolites. Furthermore, NLRP3 inflammasome and autophagy co-regulate CVDs by enhancing autophagic processes, inhibiting inflammasome activity, and reducing inflammatory responses, thus playing a pivotal role in the disease's pathophysiology. Certain pharmacological agents have been shown to inhibit NLRP3 inflammasome activity by promoting autophagy, thereby ameliorating disease pathology. This review underscores the critical roles of NLRP3 inflammasome and autophagy in CVDs and examines the regulatory effects of specific drugs on these processes.
INTRODUCTION:Chemotherapy-induced neutropenia (CIN) and its severe complication, febrile neutropenia, remain major challenges in oncology. Although granulocyte colony-stimulating factors (GCSFs) have reduced the incidence of these complications, limitations related to dosing schedules, polyethylene glycol (PEG)-associated concerns, and pharmacokinetic variability persist. Efbemalenograstim alfa (F-627) is a novel non-PEGylated Fc-fusion G-CSF designed for once-per-cycle administration. This systematic review and meta-analysis evaluated the efficacy and safety of efbemalenograstim alfa compared with placebo or standard G-CSFs in patients at risk of chemotherapy-induced neutropenia. METHODS:A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD42024628001). MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to 22 October 2025. Randomized controlled trials evaluating efbemalenograstim alfa in patients receiving myelotoxic chemotherapy were included. Efficacy outcomes included duration of severe neutropenia (DSN), incidence of severe neutropenia (ISN), and depth of absolute neutrophil count (ANC) nadir. Safety outcomes included adverse events, serious adverse events, and treatment discontinuations. Random-effects meta-analyses were performed. RESULTS:Five randomized controlled trials involving approximately 800 patients with breast cancer receiving myelotoxic chemotherapy were included. Compared with placebo or standard GCSFs, efbemalenograstim alfa demonstrated comparable efficacy in reducing DSN during the first chemotherapy cycle (MD -0.32 days; 95% CI -0.79 to 0.14) and ISN (RR 0.86; 95% CI 0.73-1.03). A significant improvement in ANC nadir was observed (MD +0.40 ×10⁹/L; p = 0.0002). Rates of serious adverse events (RR 0.71; 95% CI 0.29-1.70), adverse events, and treatment discontinuations were comparable between groups. Heterogeneity was primarily attributable to the inclusion of a placebo-controlled study. CONCLUSION:Efbemalenograstim alfa demonstrated efficacy and safety comparable to currently available long-acting G-CSFs for the prevention of chemotherapy-induced neutropenia. Its Fc-fusion structure enables once-per-cycle administration without PEGylation, supporting its potential as an alternative long-acting G-CSF. Further studies are needed to evaluate long-term outcomes and real-world effectiveness.
BACKGROUND:Avacopan, an oral C5a receptor antagonist, has been identified as a promising glucocorticoid-sparing agent in the management of ANCA-associated vasculitis (AAV). Although individual randomized controlled trials (RCTs) have indicated its therapeutic potential, there remains a need for comprehensive integration of efficacy and safety data to guide clinical decision-making. METHODS:We performed a meta-analysis of three pivotal RCTs-CLASSIC (n = 42), CLEAR (n = 67), and ADVOCATE (n = 331)-including a total of 440 individuals diagnosed with AAV. Primary endpoints encompassed clinical response, sustained and early remission rates, changes in renal function, as well as safety outcomes such as serious adverse events, infections, organ toxicity, hematologic complications, and glucocorticoid-related adverse effects. Summary effect estimates were derived using risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI). Study heterogeneity was quantified using the I² statistic and corresponding p-values. RESULTS:Avacopan was associated with efficacy outcomes that were equivalent to or exceeded those achieved with standard-of-care regimens. Clinical response (RR = 1.08; 95% CI: 0.98-1.19) and early remission (RR = 2.85; 95% CI: 0.95-8.54) favored avacopan. Improvements in renal parameters, including eGFR and renal response, were consistent but modest. Notably, avacopan substantially decreased glucocorticoid-related adverse events (RR = 0.78; 95% CI: 0.70-0.87; p <0.0001), particularly the incidence of diabetes, psychiatric complications, and general GC toxicity. Avacopan did not result in any significant increase in serious infections, mortality, or treatment discontinuations. CONCLUSIONS:Avacopan represents a highly effective and safer option compared to traditional glucocorticoid-based regimens for AAV. The capacity to sustain disease remission with reduced steroid-associated harm highlights its potential utility in evolving vasculitis treatment strategies.
INTRODUCTION:Atrial fibrillation is the most common sustained cardiac arrhythmia, primarily caused by arrhythmogenic activity within the pulmonary veins (PVs). Enhanced ketone body utilization can prevent heart failure by reducing inflammation and oxidative stress, factors crucial for atrial fibrillation pathogenesis. However, the role of ketone bodies in PV arrhythmogenesis remains unclear. This study investigated the effect of 3-hydroxybutyrate (3-OHB), the most abundant ketone body, on PV arrhythmogenesis and explored the underlying mechanisms. METHODS:Using conventional microelectrodes and the patch-clamp technique, we analyzed electrophysiological characteristics and ionic currents in isolated rabbit PV tissues and single PV cardiomyocytes. RESULTS:The effects of 3-OHB (10 mm) on reactive oxygen species (ROS) production, calcium homeostasis, and phosphorylated calcium/calmodulin-dependent protein kinase II (CaMKII) expression were analyzed through confocal microscopy and Western blotting. The results indicated that 3-OHB dose-dependently reduced PV spontaneous activity, contractility, and diastolic tension. However, these effects were blocked by KN93 and AIP, a CaMKII inhibitor. Moreover, 3-OHB reduced late sodium and L-type calcium currents in PV cardiomyocytes; these effects were blocked by KN93 and AIP. Furthermore, 3-OHB reduced cytosolic ROS levels and phosphorylated CaMKII expression. CONCLUSION:3-OHB prevents PV arrhythmogenesis by modulating ionic currents, reducing ROS production, and regulating CaMKII signaling. Thus, 3-OHB holds promise as an antiarrhythmic agent.
INTRODUCTION:Anaplastic lymphoma kinase (ALK) mutations are key oncogenic drivers in non-small-cell lung cancer (NSCLC). Although ALK tyrosine kinase inhibitors (TKIs) elicit high initial response rates, relapse due to acquired resistance is common. Conventional approaches fail to resolve tumor heterogeneity and epigenetic control, necessitating multi-omic integration to dissect molecular differences between ALK-mutant and wild-type (WT) tumors. METHODS:Single-cell RNA sequencing (scRNA-seq) and matched chromatin accessibility (scATAC-seq) data of 5 WT and 4 ALK-mutant NSCLC samples from GEO (GSE274934) were integrated. "Seurat" and "Harmony" packages in R were used for data preprocessing and batch correction. "Monocle" package reconstructed epithelial differentiation trajectories. "CellChat" package delineated cell-cell communication. "Signac" package integrated multiple omics data and analyzed the differentially accessible chromatin regions. Motif enrichment based on the JASPAR database identified key transcription factors. The role of CEACAM6 in the malignant progression of ALK-mutant-mutant NSCLC was assessed by qRT-PCR, CCK-8, colony formation, and wound-healing assays. RESULTS:ALK-mutant epithelial cells exhibit disrupted differentiation trajectories, characterized by loss of SPINK1 expression and pan-expression of MARCKSL1. ALK-mutant cells relied on CEACAM5/6 signaling for communication; WT cells primarily engaged in multidirectional MIF interactions. ALK-mutant cells showed increased global chromatin accessibility. Motif analysis revealed enrichment of polycomb repressive complex (PRC) pathway components and EGR1 binding sites (survival/drug resistance-associated) in ALK-mutant cells, whereas WT cells specifically enriched KLF5, ZNF148, and GLIS3 motifs. In vitro, CEACAM6 expression was significantly upregulated in ALK-mutant compared to WT cells. CEACAM6 knockdown significantly inhibited cell proliferation and migration, and reduced p-AKT and EGR1 protein levels, indicating that CEACAM6 promotes malignant progression of ALK-mutant NSCLC through the AKT-EGR1 signaling axis. CONCLUSION:ALK mutations drive tumor stemness and drug resistance by blocking epithelial cell differentiation, activating CEACAM6-mediated signaling, enhancing chromatin accessibility, and remodeling the EGR1/PRC regulatory network. Targeting CEACAM6 and its downstream effector EGR1 may represent an effective strategy to overcome ALK-TKI resistance.
INTRODUCTION:A serious complication of sepsis that directly impacts patient outcomes is intestinal barrier disruption. Although the polyphenolic molecule resveratrol (RE) is well known for its anti-inflammatory and antioxidant properties, its specific role in targeting the NADPH oxidase 1 (NOX1)/sirtuin 1 (SIRT1) pathway to protect against sepsis-induced intestinal barrier failure remains unexplored. Therefore, this study aimed to comprehensively investigate this novel mechanism. METHODS:The lipopolysaccharide (LPS)-treated Caco-2 cells and sepsis mouse models (cecal ligation and puncture) were utilized to assess the protective effects of RE. Quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, histological analysis, immunohistochemistry, and Western blot were employed to examine inflammatory cytokine levels, autophagy markers, and intestinal barrier function. The roles of NOX1 and SIRT1 in RE-mediated protection were explored through NOX1 overexpression and related molecular analyses. RESULTS:RE significantly improved survival rates in sepsis mice, reduced inflammatory cytokines, and restored intestinal barrier function. RE reversed the increase of NOX1 and the decrease of SIRT1 in sepsis. Histological analysis data showed that RE protected the intestinal structure, maintained the expressions of tight junction proteins, and alleviated intestinal damage. In LPS-treated Caco-2 cells, RE inhibited inflammation, promoted autophagy, and suppressed reactive oxygen species production. NOX1 overexpression partially offset the protective effects of RE. CONCLUSION:By modifying the NOX1/SIRT1 signaling pathway, RE protects against sepsis-induced intestinal barrier failure. These results underline that the NOX1/SIRT1 pathway is instrumental in autophagy and inflammation control and that RE may be a viable treatment approach for sepsis-related intestinal damage.
BACKGROUND:Wedelolactone (WED) is a polyphenolic compound with a coumarin skeleton isolated from marigold. Despite its wide application in traditional medicine, its mechanisms of action and safety profile require further investigation. SUMMARY:The key contributions of this review lie in: (1) the first systematic integration of WED's multi-target mechanisms across diseases through the AMPK/NF-κB/NLRP3 network; (2) clarification of its dose-effect relationship (effective therapeutic window: 5-100 mg/kg) and toxicity thresholds; (3) proposal of clinical translation strategies, including nanodelivery systems to address bioavailability issues. Recent studies revealed novel mechanisms such as WED's inhibition of ferroptosis via GPX4 and modulation of the FXR-bile acid axis, demonstrating efficacy in acute lung injury and liver fibrosis. KEY MESSAGES:This article provides a comprehensive framework integrating mechanistic insights and translational research for WED's clinical development.
INTRODUCTION:Escitalopram oxalate (ESC) was extensively reported to improve insomnia in patients with depression/anxiety. The serotonin transporter gene (SLC6A4) was involved in regulating insomnia. However, it is still unclear whether ESC improves insomnia by regulating SLC6A4 expression. Therefore, this study aimed to investigate whether ESC improves insomnia by regulating SLC6A4 based on clinical and animal experiments. METHODS:The clinical and animal experiments were involved in this study. For clinical experiments, after all 110 participants were divided into four groups, the portable sleep electroencephalogram monitor, HAMA14 scale, and HAMD24 scale were used to evaluate patients' sleep quality, anxiety, and depression. For animal experiments, after all 18 ICR male mice were randomly divided into three groups (n = 6), the sodium pentobarbital-induced sleeping test, locomotor activity test, elevated plus maze, and open field test were used to evaluate mice's sleep quality and anxiety- and depression-like behaviors. The H&E staining was used to determine pathological injuries in mice's hippocampal tissues. The ELISA kits were adopted to detect the 5-HT, norepinephrine (NE), gamma-aminobutyric acid (GABA), and glutamate (Glu) levels in the hypothalamus tissue and the corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) levels in the serum. The PubChem, DrugBank, and Therapeutic Target Database were employed to predict the potential targets of ESC. The immunohistochemical staining and Western blot were applied to assay the SLC6A4, 5-HTR1A, and 5-HTR2A expression levels in the hippocampal tissues of mice. RESULTS:ESC shortened the sleep latency, extended the sleep time, enhanced the sleep efficiency, and improved anxiety and depression in patients and mice. ESC mitigated the pathological injuries in mice's hippocampal tissues. ESC effectively regulated mice's neurotransmitter levels and hypothalamic-pituitary-adrenal (HPA) axis homeostasis, including upregulating 5-HT and GABA and downregulating NE, Glu, CRH, ACTH, and CORT. Moreover, SLC6A4 was predicted as the potential target of ESC. ESC prominently inhibited SLC6A4 expression (p < 0.001) and regulated 5-HTR1A and 5-HTR2A expression (p < 0.001) in hippocampal tissues. CONCLUSION:Taken together, ESC was suitable for treating insomnia in the clinic and improved insomnia by targeting SLC6A4 to regulate the HPA axis in mice.
INTRODUCTION:High-risk neuroblastoma is a difficult-to-treat cancer with high rates of recurrence and treatment resistance, likely driven by a population of cancer stem cells. Multiple previous studies have suggested that the use of mevalonate pathway inhibitors, such as statins and bisphosphonates, may have anticancer activity against high-risk tumors. METHODS:We aimed to observe the use of mevalonate pathway inhibitors against the cancer stem cell population of high-risk neuroblastoma cell lines SH-SY5Y, SK-N-AS, and SK-N-BE(2)-C using spheroid-based assays. RESULTS:We observed significant reductions in spheroid formation capability, stem cell frequency, and stemness properties of these neuroblastoma cancer stem cells with fluvastatin and zoledronate treatment. CONCLUSION:Treatment with mevalonate pathway inhibitors leads to reduced neuroblastoma cancer stem cell function through reductions in protein geranylgeranylation.
Background: Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies beyond conventional treatments. The increasing interest in natural and synthetic antiproliferative compounds is driven by their ability to target oncogenic pathways implicated in tumor progression, metastasis, and drug resistance. This review explores the potential of bioactive phytochemicals and molecularly targeted therapies, particularly epidermal growth factor receptor (EGFR) inhibitors, in modulating cancer cell survival, proliferation, and immune evasion. A central focus is placed on the phosphoinositide 3-kinases (PI3Ks)/protein kinase B (AKT), JAK/STAT, and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways, which are frequently dysregulated in therapy-resistant cancers, particularly head and neck cancer. Summary: Emerging evidence suggests that phytochemicals such as curcumin, resveratrol, and flavonoids not only suppress oncogenic signaling but also enhance apoptosis, inhibit epithelial-mesenchymal transition, and regulate oxidative stress responses. Additionally, recent preclinical and clinical studies indicate that combinatorial applications of phytochemicals with targeted agents can sensitize resistant tumors to chemotherapy and immunotherapy, thereby improving therapeutic efficacy. However, a major challenge limiting the clinical translation of phytochemicals is their low bioavailability and rapid metabolism. Advances in nanoparticle-based drug delivery, synthetic derivatives, and CRISPR-mediated genome editing offer promising solutions to overcome these limitations, ensuring optimal stability, targeted delivery, and enhanced anticancer activity. Key Messages: By integrating traditional phytotherapy with modern molecular oncology, this review highlights novel synergistic strategies that may revolutionize cancer treatment, paving the way for personalized anticancer therapeutics. DBCs and herbal medicine influence key oncogenic pathways, including EGFR, PI3K/AKT, and MEK/ERK. Human papillomavirus (HPV)-positive and HPV-negative tumors exhibit distinct molecular profiles, affecting their response to conventional treatments and adjunctive therapies. Polyphenols such as curcumin, resveratrol, and quercetin, along with herbal extracts including Scutellaria baicalensis and Camellia sinensis, demonstrate the ability to modulate oxidative stress, apoptosis, and immune responses while reducing therapy resistance. Nanoparticle-based formulations improve the bioavailability of these compounds, enhancing their anticancer effects. However, their effectiveness varies based on the HPV status of the tumor, with HPV-positive cancers showing greater sensitivity to immune-modulating compounds. .
INTRODUCTION:Proton-pump inhibitor (PPI) monotherapy is standard for artificial ulcer healing after gastric endoscopic submucosal dissection, but evidence on the efficacy of PPI combined with gastric mucosal protectants remains inconclusive. This network meta-analysis aimed to compare the efficacy of 10 mucosal protectants combined with PPIs. METHODS:We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until January 2025. Included were 20 randomized controlled trials (n = 2,000) comparing PPI monotherapy versus PPI combined with protectants (e.g., rebamipide, ecabet, polaprezinc) or active controls. Primary outcomes included ulcer area reduction, healing rates (4/8 weeks), longest ulcer diameter, and bleeding risk. Frequentist random-effects models synthesized risk ratios (RRs) and MDs with 95% CIs. Consistency was evaluated using design-by-treatment interaction and node splitting. Risk of bias (RoB 2.0) was assessed at the outcome level. Certainty of evidence was graded with GRADE. RESULTS:Bismuth subcitrate-magnesium granules (BMG) + PPI most effectively reduced 4-week ulcer area (MD: -62.50 mm2, 95% CI: -87.25 to -37.75 vs. PPI; SUCRA = 94%). Ecabet sodium (EB) + PPI achieved the highest 8-week healing rate (RR: 7.71, 95% CI: 5.52-9.91). Hydrotalcite (HT) + PPI best reduced ulcer diameter (MD: -1.87 mm), while teprenone (TN) + PPI optimally prevented bleeding (RR: -3.41, 95% CI: -5.43 to -1.38). Rebamipide + PPI showed efficacy heterogeneity, particularly in large ulcers (>40 mm). CONCLUSIONS:PPI-based combinations likely accelerate healing versus PPI alone, but conclusions are hypothesis generating given indirect evidence and regional concentration of trials. Combination therapy outperforms PPI monotherapy. BMG + PPI is optimal for early ulcer healing, EB + PPI for long-term healing, HT + PPI for diameter reduction, and TN + PPI for bleeding prevention. Stratified regimens by ulcer characteristics are recommended.
Introduction: The administration of medication through feeding tubes (FTs) represents a critical aspect of routine nursing practice. Although guidelines recommend the separate administration of medications to minimize potential interactions, it is common practice in the clinical settings for medications to be combined and administered simultaneously. Since there is a lack of data on this topic, this study assesses the stability of drugs crushed and mixed in water solution concurrently for administration through FT. Methods: The drug compatibility was evaluated in vitro by monitoring the changes in drug content in water solution over time and identifying potential degradation products using a high-performance liquid chromatography system. Results: The majority of drugs (acetylsalicylic acid, clopidogrel, atorvastatin, furosemide, and prasugrel) maintained their stability during the entire preparation process. The only medication that showed degradation over time was pantoprazole (especially when combined with acetylsalicylic acid and clopidogrel), which was attributed to the acidic environment. The remaining drugs (acetylsalicylic acid, clopidogrel, atorvastatin, furosemide, and prasugrel) maintained their stability during the entire preparation process. Conclusion: This study proves that most drugs can be prepared and administered simultaneously, with the exception of acid-labile drugs, which undergo significant degradation in acidic solutions.
BACKGROUND:Colorectal cancer (CRC) is one of the most common malignancies worldwide, and the liver is its main site of distant metastasis. Colorectal cancer liver metastasis (CRLM) is a major cause of CRC-related death. Current treatments, including surgery, chemotherapy, and immunotherapy, have limited efficacy and often cause substantial side effects. SUMMARY:This review examines the emerging role of traditional Chinese medicine (TCM) in managing CRLM, focusing on its ability to modulate the tumor microenvironment (TME) by inhibiting epithelial-mesenchymal transition, suppressing angiogenesis, and reversing immune evasion. TCM provides a holistic, multi-targeted approach, but most supporting evidence comes from preclinical studies in cell and animal models, with limited clinical validation. KEY MESSAGES:TCM shows promise for targeting the CRLM-related TME. Most evidence is preclinical; well-designed clinical trials are urgently needed. Standardization, pharmacokinetics, and regulatory issues remain major barriers to clinical application.
OBJECTIVE:This study aimed to unveil the impact of optimal pulse technology (OPT) combined with tobramycin and dexamethasone eye ointment on the ocular surface disease index (OSDI) and related outcomes in patients with blepharokeratoconjunctivitis (BKC). METHODS:Ninety-six BKC patients treated at our hospital from September 2022 to September 2023 were divided into a control group (n = 48) and an observation group (n = 48) by a random number table. Both groups received fluorometholone and sodium hyaluronate eye drops. The control group additionally applied tobramycin and dexamethasone eye ointment to the lid margin twice daily, while the observation group underwent OPT on this basis. The clinical efficacy and safety, OSDI, conjunctival hyperemia score, lid margin alteration score, meibomian gland yield secretory score (MGYSS), Demodex mite count, and tear break-up time (TBUT) were compared between the two groups before treatment and at 4 and 8 weeks post-treatment. Additionally, the National Eye Institute Visual Function Questionnaire-25 (NEIVFQ-25) scores were assessed before and after treatment. RESULTS:The total effective rate in the observation group was 100.00% (48/48) at 8 weeks post-treatment, higher than 89.58% (43/48) in the control group (P < 0.05). The OSDI, conjunctival hyperemia score, lid margin alteration scores, MGYSS, and Demodex mite count all decreased in both groups at 4 and 8 weeks post-treatment compared to baseline, with greater improvements in the observation group(P < 0.05). TBUT and NEIVFQ-25 scores increased in both groups at 8 weeks post-treatment compared to baseline, with the observation group achieving better outcomes than the control group (P < 0.05). CONCLUSION:The addition of OPT to standard therapy for BKC is safe and provides superior short-term efficacy. It can alleviate lid margin inflammation, improve ocular surface symptoms, and enhance visual-related quality of life.
INTRODUCTION:Alpha-linolenic acid (ALA) is a well-known n-3 polyunsaturated fatty acid. Our previous study showed that ALA inhibits coronary contractions induced by U46619 (a thromboxane A2 analog) and prostaglandin F2α (PGF2α) in pigs by antagonizing prostanoid TP receptors. In this study, we investigated the inhibitory effects of ALA on pig basilar artery contractions and explored the underlying mechanisms. METHODS:The effects of ALA on contractions of pig basilar arteries were assessed. The effects of K+ channel inhibitors on ALA-mediated attenuation were also evaluated. RESULTS:ALA inhibited TP receptor-mediated contractions induced by U46619 and PGF2α in a concentration-dependent manner. It shifted the U46619 concentration-response curve to the right and reduced the maximal contraction. The slope of the regression line in the Schild plot analysis exceeded unity, although the difference was not statistically significant. ALA also inhibited PGF2α-induced contractions (in the presence of SQ 29,548, a TP receptor antagonist) and endothelin-1-induced contractions, without affecting those induced by high-KCl. Among the tested K+ channel inhibitors, Ba2+, an inhibitor of inwardly rectifying K+ (Kir) channels, most potently attenuated ALA's inhibitory effect on PGF2α-induced contractions in the presence of SQ 29,548. CONCLUSION:These findings indicate that ALA potently inhibits contractions induced by potentially spasmogenic substances in the pig cerebral artery. The inhibitory mechanisms likely involve both antagonism of prostanoid TP receptors and activation of Kir channels.
The article "Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer Patients: What Is the Better Choice?" [Oncology 2021; https://doi.org/10.1159/000521252] by Alessandra Fabi, Mariangela Ciccarese, Sinome Scagnoli, Michelangelo Russillo, Francesco Schettini, Giuseppe Buono, Vito Lorusso, Katia Cannita, Grazia Arpino, Simonetta Stani, Michela Palleschi, Rosalba Rossello, Giuseppina Sarobba, Agnese Fabbri, Marianna Giampaglia, Patrizia Pellegrini, Vincenzo Adamo, Francesca Morelli, Vittoria Barberi, Gianluigi Ferretti, Giovanna Catania, Simona Pisegna, Francesco Cognetti and Diana Giannarelli has been retracted by the Publisher and the Editor.After peer review, the accepted, unedited manuscript was published online as Early View. The authors did not respond to our requests and communication regarding the production process of their article despite extensive attempts at contact. As the article has not been approved by the authors for publication, we cannot publish the final version. To avoid confusion for readers we are retracting the Early View accepted, unedited manuscript.The authors did not respond to correspondence about the retraction.
