Objective To assess the clinical efficacy of sodium hyaluronate （0.3%） eye drops combined with herbal self-heating steam eye mask in the treatment of dry eye disease. Methods A prospective randomized controlled clinical trial was performed on 60 patients diagnosed with dry eye at the ophthalmic clinic of a Grade A, Class Ⅲ hospital in Shanghai from June 2023 to September 2024. Specifically, patients were randomly divided into control group and study group. Patients in the control group were treated with sodium hyaluronate （0.3%） eye drops for six weeks; while in the study group, patients received the eye drops combined with the herbal self-heating steam eye mask mainly containing powders of Flos Buddlejae. Subsequently, comparisons and analysis were performed before and after treatment between the two groups in the clinical symptom questionnaire score traditional Chinese medicine （TCM syndrome score），the Chinese dry eye questionnaire score and determination of tear film fluorscein breakup time （FBUT）, and curative effect. Results The quality control standard of the herbal powder in the self-heating steam eye mask was established through TLC and HPLC, and good heating behavior of the herbal self-heating steam eye mask was ascertained heating temperature （43±5）℃; heating duration （≥20 min）, meeting requirements of the product quality control. After treatment for 6 weeks, FBUT was increased, while TCM syndrome score and the Chinese dry eye questionnaire score were both decreased in the study group （P<0.001）. Besides, compared with the control group, TCM syndrome score and the Chinese dry eye questionnaire score were much lower, while the FBUT were higher in the study group （P<0.001）. Moreover, the overall response rate in the study group （81.7%） was much better than that in the control group （25.9%）. Conclusion The combination of sodium hyaluronate （0.3%） eye drops with herbal self-heating steam eye mask could be applied to the clinical treatment of dry eye disease due to its good clinical effects on relieving dry eye symptoms.

Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

Background: s/Aims: Postoperative pancreatic fistulas (POPF) remain a major cause of morbidity and mortality following pancreatoduodenectomy (PD). Pancreatogastrostomy (PG) and pancreatojejunostomy (PJ) are the two most commonly used reconstruction techniques, yet evidence favoring one over the other is inconclusive. This study evaluates postoperative outcomes following open PD at a single institution that transitioned from PG to PJ as the preferred reconstruction method. Methods: This retrospective comparative study included patients who underwent PD between April 2005 and August 2022. Of 757 patients identified, 522 met the inclusion criteria. Propensity score matching (PSM) was performed to adjust for clinically relevant covariates. Primary endpoints were clinically relevant (CR) POPF (grade B/C) and Clavien–Dindo (CD) grade ≥ 3 POPFs. Secondary outcomes included post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), systemic complications, length of hospital stay, and mortality. Results: Overall, CR-POPF and CD grade ≥ 3 POPFs occurred in 21.3% and 8.0% of patients, respectively. Thirty-day and in-hospital mortality rates were 3.1% and 4.2%. After PSM, 368 patients (184 PG and 184 PJ) were analyzed. Grade B POPFs were more frequent following PJ than PG (24.5% vs. 15.8%, p < 0.001). Although CR-POPF and CD grade ≥ 3 POPFs were numerically higher in the PJ group, differences were not statistically significant. In contrast, DGE, PPH, and in-hospital mortality were significantly higher following PG (37.0% vs. 25.0%, p = 0.025; 16.3% vs. 8.7%, p = 0.025; and 7.6% vs. 2.7%, p = 0.049, respectively). Conclusions PG was associated with a lower incidence of grade B POPFs but higher rates of DGE, PPH, and in-hospital mortality.

Introduction: The 2021 IDF-DAR risk calculator had been previously evaluated in multiple studies and subsequently widely accepted and applied in clinical practice as a practical standardized tool for patient risk stratification. Recently updated, the 2026 IDF-DAR Risk calculator enables a more individualized, evidence-related evaluation of patientrelated and disease-related risk factors, incorporating modern diabetes technologies, including continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and advanced insulin formulations to enhance risk stratification. This tool allows medical professionals to tailor Ramadan practices based on overall factors toward promoting safe fasting. Methodology: This prospective multicentre observational study recruited adults with Type 1 and Type 2 diabetes attending public hospitals nationwide. People with diabetes (PwD) intending to perform Ramadan fasting were invited to participate and assessed using the 2026 IDF-DAR Risk Calculator in the 6-week pre-Ramadan period between 30th January and 19th March 2026. Results: A total of 458 PwD were evaluated and stratified into low (15.7%), moderate (41%), and high risk (43.3%) categories. Most participants had Type 2 diabetes (83.6%), with 60.3% having a disease duration exceeding 10 years and 43% exhibiting poor glycemic control (hemoglobin A1c >9%). Insulin therapy was used by 76.4% of participants, including two individuals with Type 1 diabetes using AID systems. Most participants reported no recent hypoglycemia (76.4%), 81.0% performed glucose monitoring, and 3.3% used CGM. Severe comorbidities were uncommon, with 1.1% having unstable macrovascular disease and 4.4% advanced chronic kidney disease (estimated glomerular filtration rate <30). Notably, 72.2% received structured Ramadan education. Conclusion Majority of PwD attending tertiary diabetes clinics were in the moderate- to high-risk category and intended to fast despite medical advice against fasting in some cases. Although most participants were on insulin therapy, hypoglycemia was low in the pre-Ramadan period. Integration of modern technologies, advanced insulin therapies, and structured education may support safer fasting practices.
Risk Assessment ; Diabetes Mellitus ; Hospitals ; Fasting

Objective This study aimed to investigate the genetic diversity, differentiation, and population structure of Aedes albopictus across different geographical regions in Shandong Province, and to explore the relationship between genetic diversity and geographical distribution. Methods Between July and August 2024, ten Ae. albopictus populations were sampled from seven cities in Shandong Province. Genomic DNA was extracted from individual mosquitoes, and the mitochondrial cytochrome c oxidase subunit I(COⅠ)gene was amplified using PCR and sequenced. The obtained sequences were verified using BLAST and analyzed with MAFFT, MEGA 11, DnaSP v6.12, Arlequin 3.5, PopART 1.7, STRUCTURE 2.3.4 and the R packages adegenet and vegan to assess genetic diversity and population structure. Results A total of 229 COⅠ sequences(662 bp) was obtained, revealing ten variable sites with no insertions or deletions. The overall base composition showed an AT bias of 67.7%. Haplotype analysis identified 11 haplotypes, with Hap2 being the dominant and most widely distributed haplotype across all populations. Neutrality tests showed significant population expansion only in the Rizhao population. Mantel testing result revealed that geographical distance does not significantly impede gene flow. Overall, genetic differentiation among populations was low, indicating frequent gene flow. When combined with additional samples from Shanghai, Fujian, Guangdong, Yunnan, Hainan and Guangxi, STRUCTURE, UPGMA and DAPC analyses revealed two primary genetic clusters of Ae. albopictus. Conclusions Ae. albopictus populations in Shandong Province exhibit frequent gene flow, low genetic differentiation, and relatively low overall genetic diversity. However, the Rizhao population showed signs of recent expansion, highlighting the need for enhanced surveillance and targeted control measures in this area.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

[This corrects the article DOI: 10.1016/j.apsb.2021.08.008.].