Reporting adverse drug reactions (ADRs) by patients may contribute to the improvement of drug safety. However, underreporting of ADRs is estimated to be the main problem of the pharmacovigilance system. While the concern about and contribution to pharmacovigilance of Turkish health professionals is disappointing, drawing the picture of Turkish consumers' knowledge, attitude and practices is paramount to improve the contribution of this group. We evaluated the knowledge, attitude and practices regarding pharmacovigilance among Turkish inpatients in a university hospital in Turkey. An observational, cross-sectional study was performed by a face-to-face questionnaire in 260 inpatients. The questionnaire consisted of demographic data and 15 and 9 items regarding knowledge and attitude and practices, respectively. The numerical and categorical data were presented as mean ± standard error of the mean (S.E.M.) and number (percentage). Comparisons between two groups were analysed by Mann-Whitney U test and those between more than two groups by Kruskal-Wallis test and Dunn-Sidak test. The mean score of knowledge level (1.38 ± 0.12) was far below that of maximum score (15 points). Although 245 of 260 inpatients (94.62%) were aware of side effects, only 18 of them (6.92%) had heard about the pharmacovigilance term and the Turkish Pharmacovigilance Centre. Ten of 18 subjects (55.56%) knew that they could directly report ADRs via the reporting form. 42% of inpatients had experienced ADRs in the past, 69.16% of them preferred to consult the doctor of concern, stopping the drug being the most selected intervention (60.75%). Among the 18 subjects aware of the Turkish Pharmacovigilance Centre, only 11.11% reported ADRs to the center. The knowledge, attitude and practices of Turkish inpatients regarding pharmacovigilance are insufficient and should be stimulated through various means to increase the rate of spontaneous reporting of ADRs and to ensure a more proactive attitude.

Uterine fibroids involve abnormal cell proliferation and fibrosis, with epithelial-mesenchymal transition (EMT) playing a key role. Mitochondrial-endoplasmic reticulum stress and related signaling pathways are implicated in this process, but the potential of natural extracts for modulation remains underexplored. This study aimed to investigate whether Atractylodes macrocephala extract can reverse EMT progression in uterine fibroids by regulating mitochondrial-endoplasmic reticulum stress via relevant signaling pathways. A mouse model of uterine fibroids was established and divided into normal, model, and Atractylodes macrocephala extract groups. Measurements included uterine weight, organ coefficient, cell proliferation, and apoptosis rate. Caspase-4 activity analysis, Western blotting, and immunofluorescence microscopy were used to assess protein and gene expression related to EMT, apoptosis, and signaling pathways. The uterine fibroid model was successfully established. Treatment with Atractylodes macrocephala extract significantly inhibited uterine fibroid cell proliferation, promoted apoptosis, and reduced fibrosis. Mechanistically, the extract ameliorated EMT by effectively suppressing PI3K/Akt pathway activity. It concurrently exacerbated endoplasmic reticulum stress (indicated by increased Caspase-4 activity) to promote apoptosis while enhancing lysosome generation. Atractylodes macrocephala extract inhibits proliferation, promotes apoptosis, and reduces fibrosis in uterine fibroids by suppressing the PI3K/Akt pathway and enhancing endoplasmic reticulum stress. These findings provide a novel strategic basis for developing natural targeted therapies against uterine fibroids.

Parkinson's disease (PD) is a common neurodegenerative disorder involving multiple pathological processes. Bergapten (BeG) exhibits various pharmacological activities, including anti-inflammatory, antioxidant and neuroprotective effects, but its mechanism of action in PD remains unclear. This study aimed to investigate the neuroprotective effects and underlying mechanisms of BeG in PD models. An in vitro neuroinflammation model was established using LPS-treated astrocytes. In-vitro studies demonstrated that BeG counteracted LPS-induced astrocyte activation by reducing the expressions of GFAP, inflammatory mediators (IL-6, TNF-α, IL-1β), and A1 polarization markers. It alleviated ERS (as indicated by reduced levels of GRP78, CHOP) and apoptosis (as shown by changes in Bax, caspase-3) while enhancing Bcl-2. Mechanistically, BeG suppressed LCN2 expression and JAK2/STAT3 phosphorylation, with LCN2 overexpression attenuating its protective effects. In MPTP-treated mice, BeG improved motor function, preserved dopaminergic neurons, and reduced astrocyte activation and A1 polarization. It increased neurotrophic factors (BDNF, GDNF) while decreasing inflammation, ER stress and apoptotic markers. The inhibition of the LCN2/JAK2/STAT3 pathway was consistently observed in both models, suggesting its central role in BeG's neuroprotective mechanism. These findings suggest that BeG exerts neuroprotective effects in PD by inhibiting the LCN2/JAK2/STAT3 signaling pathway, thereby effectively inhibiting astrocyte activation-mediated neuroinflammation and ERS.

Recurrent pneumonia in the elderly can repeatedly damage lung function and reduce quality of life, posing certain challenges to clinical treatment. To analyze the synergistic immune regulatory effects of Cistanche deserticola, Schisandra chinensis and Cornus officinalis on elderly patients with recurrent pneumonia. A total of 165 patients with recurrent pneumonia from Chengde Medical University from January 2024 to January 2025 were recruited, 158 were enrolled after exclusions, 8 lost to follow-up, and 150 finally analyzed. The 150 patients were divided into MC group (n=75) and MA group (n=75). Both groups were treated with Ma Xing Shi Gan Tang and Azithromycin, while the MC group was additionally treated with Cistanche deserticola, Schisandra chinensis and Cornus officinalis. The main evaluation includes the Traditional Chinese Medicine Syndrome Score (TCMSS), lung function indicators, inflammation indicators, immune indicator levels and clinical efficacy of two groups. Secondary outcomes include quality of life scores, incidence of complications and adverse reactions. After treatment, the lung function indicators, immune indicators and clinical efficacy in MC group were higher than in the CC group; the TCMSS and inflammatory indicators were lower in the CC group (P>0.05). No significant difference in quality of life score, incidence of complications and adverse reactions between the two groups (P<0.05). This method has a good immunomodulatory effect on elderly patients with recurrent pneumonia and is worthy of further promotion and application.

Early Alzheimer's disease (AD) treatments include donepezil, memantine and sodium oligomannate, but their comparative effects on cognitive decline and neuroinflammation are understudied. This study compares three drugs' validity in improving two aspects in early AD patients. 132 early AD patients from XX Hospital (Jan 2022-Dec 2024) were retrospectively included. After exclusion, 126 patients were divided into 3 groups (42 each): Group A (donepezil), Group B (memantine), Group C (sodium oligomannate). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale--Cognitive Subscale (ADAS-cog), the Activity of Daily Living Scale (ADL), the Montreal Cognitive Assessment Scale (MoCA), levels of inflammatory mediators, including Tumour Necrosis Factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), neuronal marker levels including β-Amyloid (1-42) (Aβ42), Total tau protein (T-tau protein) and adverse reaction incidence. After treatment, compared with Group A, Groups B/C had significantly higher MMSE, ADL, MoCA, Aβ42 (all P<0.05) and lower ADAS-cog, TNF-α, IL-6, IL-8, T-tau (all P<0.05); compared with Group B, Group C had no significant difference in MMSE, ADAS-cog, ADL, MoCA (all P>0.05), but higher Aβ42 and lower TNF-α, IL-6, IL-8, T-tau (all P<0.05); adverse reaction incidence did not differ significantly among the three groups (P>0.05). Memantine and sodium oligomannate outperform donepezil in improving cognitive function and neuroinflammation, with sodium oligomannate suggesting the best effect on neuroinflammation. This study provides a scientific basis for optimizing early AD medication.

Depression is a common mental disorder. Patients with treatment-resistant depression (TRD) often experience sleep disorders (SD), which interact with each other and aggravate the deterioration of the disease. In this study, we analyzed the effect of paroxetine combined with low-dose quetiapine on patients with treatment-resistant depression complicated by sleep disorders. We divided treatment-resistant depression + sleep disorders 120 patients into a control group treated with paroxetine and a research group treated with paroxetine + low-dose-quetiapine. Hamilton Depression Scale (HAMD-17), Self-rating Anxiety and Depression Scale (SAS/SDS), Pittsburgh Sleep Quality Index (PSQI) and serum indexes (cortisol, epinephrine, thyroid hormone, etc.) were used to analyze the data. In terms of clinical efficacy, the research group demonstrated superior efficacy. Besides, the research group showed lower self-rating anxiety/depression scale scores than the control group after treatment (P<0.05). In terms of sleep quality, the Pittsburgh Sleep Quality Index of the research group also decreased more significantly compared with the control group (P<0.05). Moreover, better stress injury alleviation and endocrine function improvement were determined in the research group (P<0.05). The two groups were not statistically different in treatment compliance and adverse reactions (P>0.05). Paroxetine combined with a low dose of quetiapine is a clinically effective approach for treatment-resistant depression with sleep disorders and is recommended for clinical use.

Hypercholesterolemia is a major modifiable risk factor for cardiovascular disease, largely driven by excessive activity of 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), the rate-limiting enzyme in cholesterol biosynthesis. Although statins are effective inhibitors of this enzyme, their long-term use is often limited by their adverse effects. This has encouraged the search for safer, plant-derived alternatives. Withania coagulans, a medicinal plant rich in withanolides, has demonstrated lipid-lowering potential; however, its molecular interactions with Hmgcr remain insufficiently explored. This study aimed to identify and characterize bioactive compounds from Withania coagulans as potential natural inhibitors of Hmgcr in Mus musculus, using an integrated in silico strategy. A validated three-dimensional model of Mus musculus Hmgcr was generated using homology modeling. Twenty bioactive compounds from Withania coagulans, along with standard statins, were screened using molecular docking and ADMET profiling, following Lipinski's rule of five. High-ranking complexes were further explored using MM/PBSA and MM/GBSA binding-free energy calculations. Molecular dynamics simulations (100 ns) were performed for top-ranked selected ligand-protein complexes to assess their structural stability and interaction persistence under physiologically relevant conditions. Several Withania coagulans compounds demonstrated strong binding affinities toward the Hmgcr active site, in some cases comparable to or exceeding those of standard statins. The key interactions involved conserved catalytic residues, such as Tyr516, Met533, Ile535, Ile761, Pro812 and Gln813. Molecular dynamics analyses revealed stable complexes with low RMSD fluctuations and minimal active site flexibility, confirming sustained ligand binding. ADMET predictions suggested favorable oral absorption and acceptable drug-like properties for the leading compounds. This study highlights Withania coagulans as a promising source of natural Hmgcr inhibitors. The identified compounds exhibited stable binding, favorable pharmacokinetic profiles, and mechanistic similarity to established statins, supporting their potential for further experimental validation as cholesterol-lowering agents.

Fufang Banmao Capsule (FBC) is clinically applied in the treatment of non-small cell lung cancer (NSCLC), yet its underlying pharmacological mechanism remains to be fully elucidated. This study aimed to systematically elucidate the pharmacological actions of FBC against NSCLC by integrating network pharmacology and Mendelian randomization approaches. Active components and potential targets of FBC were retrieved from the BATMAN-TCM database, while NSCLC-related therapeutic targets were collected from OMIM, TTD, and DisGeNet. Enrichment analysis and a "Herbs-Ingredients-Targets-Pathways" network were constructed. Core targets were further identified through protein-protein interaction and Mendelian randomization analyses, followed by colocaliza tion tests and molecular docking validation. A total of 152 potential FBC targets for NSCLC were identified, with seven candidates shortlisted. Among these, TNF and PIK3CA emerged as key protective targets (P<0.0025, OR<1). Colocalization analysis suggested possible shared genetic causality of TNF and PIK3CA single nucleotide polymorphisms with increased NSCLC risk. Molecular docking confirmed strong binding interactions between these targets and active FBC compounds such as resveratrol. The findings provide a theoretical foundation and new research directions for further investigation into the anti-NSCLC mechanism of FBC, supporting future innovation in therapeutic strategies.

Early identification of high-risk individuals is essential to guide infection-prevention strategies and optimize antibiotic stewardship in this vulnerable population. To identify independent risk factors associated with hospital-acquired infections in elderly ICU patients following antibiotic use and to develop and internally validate a clinical risk prediction model for early infection detection. A retrospective cohort study was conducted in the ICU of Nanjing First Hospital, Nanjing Medical University. A total of 120 patients aged ≥65 years, with ICU stay >48 hours, no documented infection at ICU admission and antibiotic exposure within 48 hours before or at ICU admission were included. Demographic data, comorbidities, Sequential Organ Failure Assessment (SOFA) scores, antibiotic exposure characteristics, invasive device use and nutritional support were collected from electronic health records. Hospital-acquired infections occurred in 46 patients (38.3%). Independent predictors included advanced age (odds ratio [OR] 1.08 per year), higher SOFA score (OR 1.25 per point), diabetes mellitus (OR 1.45), chronic kidney disease (OR 1.65), use of central venous catheters (OR 1.75), mechanical ventilation (OR 1.85), Foley catheterization (OR 1.55), broad-spectrum antibiotic use (OR 1.50), longer antibiotic duration (OR 1.20 per day) and prolonged ICU stay (all p<0.05). The prediction model demonstrated good discrimination (AUC-ROC = 0.82), which improved slightly after variable refinement (AUC-ROC = 0.83). Cross-validated performance remained robust (AUC = 0.80). A multivariable risk prediction model using routinely available clinical parameters demonstrated good internal validity and may assist clinicians in early identification of high-risk patients, enabling targeted infection prevention and improved antibiotic stewardship.

Tryptophan 2,3-dioxygenase (TDO) is a haem-containing enzyme of the kynurenine pathway, which is imperative for tryptophan metabolism. Primarily found in the liver, TDO facilitates the breakdown of TRP into N-formyl kynurenine. TDO is regarded as a promising target for antidepressant therapies. As an enzyme responsible for tryptophan degradation, its inhibition may enhance serotonin availability, which plays a key role in mood regulation. This study identifies TDO as a potential target for central nervous system drugs (acamprosate, roxindole, and L-ascorbic acid) that may alter brain activity and potentially impact mood and behavior. The study involved male Albino Wistar rats, each weighing between 150 and 200 grams. The rats were decapitated, the livers were promptly excised within 10 seconds, and perfused in situ with ice-cold saline. The perfused livers were then immediately frozen at -80°C for subsequent analysis. In vitro TDO enzyme activity was assessed in frozen liver homogenates. Enzymatic activity was measured for both the holoenzyme and total enzyme spectrophotometrically. Molecular docking of the selected compounds with TDO was conducted using AutoDock Vina. The crystal structure of TDO was retrieved from the Protein Data Bank (PDB), while ligand structures were obtained from PubChem. In vitro experiments revealed that these drugs inhibited apoenzyme activity by 68-85%, while total enzyme activity was reduced by 34%, 38% and 37% for acamprosate, roxindole, and L-ascorbic acid, respectively. Further validation through molecular docking analysis confirmed their strong binding affinity to the TDO active site, with l-ascorbic acid showing the highest binding energy (-7.2 kcal/mol), followed by acamprosate (-6.7 kcal/mol) and roxindole (-6.4 kcal/mol). These findings suggest that acamprosate, roxindole, and L-ascorbic acid act as competitive TDO inhibitors, potentially enhancing serotonin synthesis and mitigating depressive symptoms.