The oral-gut axis links the oral and gut microbiomes, both anatomically and functionally, and its dysregulation is implicated in periodontitis and inflammatory bowel disease (IBD). Bacterial extracellular vesicles (BEVs), nano-sized particles (20-250 nm) released by diverse microbes, serve as key mediators of inter-organismal communication along this axis. Carrying virulence factors, nucleic acids, and immunomodulators, BEVs influence microbial ecology and host immunity. In the oral cavity, pathogen-derived BEVs (e.g., from Porphyromonas gingivalis) promote biofilm formation, immune evasion, and tissue destruction. In the gut, BEVs from commensals (e.g., Akkermansia muciniphila) reinforce barrier function and suppress inflammation, whereas those from pathogens exacerbate dysbiosis. Critically, BEVs mediate bidirectional crosstalk: oral pathogen BEVs can translocate to the gut and worsen IBD, while beneficial gut-derived BEVs may attenuate periodontal inflammation. This review summarizes the roles of BEVs in oral-gut communication, their involvement in inflammatory disease pathogenesis, and their potential as biomarkers and therapeutics.
Oral lichen planus is a chronic disease of the oral mucosa, with pain as one of its main symptoms. This study aimed to assess the correlation between the results of four pain intensity measures-including the Visual Analog Scale (VAS), Numeric Rating Scale (NRS), Short Form McGill Pain Questionnaire (SF-MPQ), and Verbal Rating Scale (VRS)- in a population of patients diagnosed with oral lichen planus. In this prospective observational study, 66 patients with oral lichen planus participated. Four pain assessment scales were used, including VAS, NRS, VRS, and SF-MPQ. Participants completed these assessments at baseline and again after two weeks of treatment. A paired t-test, Spearman correlation, linear regression analysis, and adjusted multiple regression analysis (regarding age and level of education) were used to analyze the data. All four scales were sensitive to changes in pain after treatment and a significant reduction in pain scores was observed (p < 0.001). There was a strong positive correlation between all scales (p < 0.001). Regression analysis showed that scores on each scale could significantly predict scores on the other scales (p < 0.001). Multiple regression analysis adjusted for age and level of education, showed the correlations between the pain scales remained strong and significant (p < 0.001). These commonly used pain assessment scales showed strong correlation with each other, and it seems that the results obtained from each might be comparable with the others. However, further researches in larger studies and different populations are needed.
The regulatory mechanisms and clinical significance of long non-coding RNAs (lncRNAs) in oral squamous cell carcinoma (OSCC) have become a research hotspot in recent years. We conducted a narrative review of PubMed, CNKI, and Wanfang databases (2014-2024). Using Boolean combinations of "lncRNA," "OSCC," and "pathogenesis," we screened original studies. Selection focused on human OSCC functional mechanisms and clinical biomarkers, while excluding papers with insufficient data or irrelevant cancer types. lncRNAs regulate gene expression and signaling pathways by interacting with their targets (including nucleic acids and proteins), playing a key role in the occurrence, development, metastasis, and drug resistance of OSCC.Advances in non-invasive testing technologies such as liquid biopsy, as well as breakthroughs in lncRNA-targeting techniques based on CRISPR and antisense oligonucleotides (ASO), have provided new tools for related research and applications. This article systematically summarizes the molecular mechanisms of lncRNA in OSCC and explores its clinical application prospects, aiming to provide direction for future theoretical research and clinical translation.
The hedgehog (Hh) signalling pathway is aberrantly activated in solid tumours. Inhibition of Hh signalling by SMO inhibitors is effective in the treatment of basal cell carcinomas and medulloblastomas whereas combination treatments may be required in other solid tumours. When given with an SMO inhibitor in preclinical models, the efficacy of paclitaxel is enhanced and there is potential reversal of mechanisms of resistance to paclitaxel supporting clinical investigation of the combination. In this phase I trial, the safety and feasibility of the oral SMO inhibitor, taladegib, was evaluated in combination with weekly paclitaxel in patients with advanced solid tumours. This was an open-label, nonrandomised, multicentre, dose escalation trial using a standard 3 + 3 design (EudraCT: 2014-004695-37 ISRCTN15903698). Primary objectives were to determine dose-limiting toxicities and the maximum tolerated dose of the combination. Patients received up to 6 cycles of paclitaxel 80 mg/m2 (day 1, 8 and 15 of a 28-day cycle). Then, 16 patients were recruited into 3 cohorts and received taladegib at 100 mg, 200 mg and 400 mg once daily, respectively. Grade 2/3 peripheral sensory neuropathy was the dose-limiting toxicity. The maximum tolerated dose of taladegib in combination with weekly paclitaxel was 200 mg once daily. Four patients had a partial response and 4 had confirmed stable disease at 16 weeks. The combination is feasible but cumulative neuropathy may limit longer term treatment. Hh signalling may be implicated in chemotherapy-induced neuropathy.
To investigate the impact of mouth breathing (MB) on the salivary microbiome in children by comparing the differences in biochemical indicators, immune proteins and microbial community structure between mouth-breathing children and nose-breathing children, as well as among mouth-breathing children with different malocclusion types. Saliva samples were collected from 30 mouth-breathing children (MB group) and 10 nose-breathing children (control group), aged 8 to 12, between August 2023 and August 2024. The MB group was further subdivided into Angle Class I, II and III malocclusion subgroups, with 10 cases each. Ion concentrations were measured using an automatic biochemical analyser, pH was determined using a pH metre, immune protein levels were assayed by enzyme-linked immunosorbent assay and the structure and diversity of the salivary microbiota were analysed using 16S rRNA high-throughput sequencing. Compared with the control group, the MB group showed no significant difference in salivary pH (P > .05), but a significantly lower chloride ion (Cl⁻) concentration (P < .05). Conversely, the concentrations of secretory immunoglobulin A (SIgA) and peroxiredoxin-5 (PRDX5) were significantly higher in the MB group (P < .05). No statistically significant differences in these indicators were observed among the different malocclusion subgroups. Spearman correlation analysis revealed a positive correlation between PRDX5 and SIgA concentrations (rs = 0.808, P < .001) and negative correlations between both PRDX5 and SIgA concentrations and Cl⁻ concentration (rs = -0.588 and -.600, respectively; P < .001) in the MB group. Microbiota analysis indicated that the species richness (Chao1 index) of the salivary microbiota was significantly higher in the MB group. At the genus level, the relative abundances of Dialister, Streptobacillus, Anaeroglobus and Scardovia were significantly increased in the MB group (P < .05). MB alters the physicochemical properties of children's saliva, triggering an enhanced local immune response and a state of oxidative stress. This leads to dysbiosis of the salivary microbial community, characterised by a higher abundance of pathogenic bacteria associated with dental caries and periodontal disease and shows a correlation with pathogens linked to upper respiratory tract inflammation. These findings suggest that MB may impact oral and potentially systemic health by disrupting the oral microenvironment.
Investigate if choice of neck management by sentinel lymph node biopsy (SLNB) or elective lymph node dissection (ELND) affects disease specific (DSS) or overall survival (OS) in cT1-T2 N0 oral cancer patients subsequently diagnosed with occult metastasis (pN+). Retrospective study of cT1-T2 N0 OSCC upstaged pathologically (pN+) by either SLNB or ELND at three major UK head and nek surgery centres between 2006 and 2021. Univariate and multivariate Cox proportional hazard regression analysed factors influencing survival. The most influential hazard ratios were selected for matched pair analysis of 4- and 6-variables. Cases were matched by a specifically designed algorithm. OS and DSS of matched-pairs were investigated by Kaplan-Meier survival analysis. Seventy-three pN+ patients were identified in the SLNB group and 153 pN+ patients in the ELND group. Matched-pair algorithm generated 69 matches across four variables (extranodal tumour extension (ENE), depth of invasion (DOI), perineural invasion (PNI) and the absence of associated dysplasia) and 70 matches at six variables (ENE, DOI, PNI and absence of associated dysplasia, LVI, non-cohesive invasive front). Matched-pair analysis of both 4 and 6 variables found no significant difference between pN+ SLNB and pN+ ELND for both 5-year DSS (71% vs. 61%, p = 0.718) and OS (71% vs. 58%, p = 0.322) CONCLUSIONS: There is no evidence to suggest the choice of neck management influences survival outcomes in early OSCC patients harbouring occult metastasis.
To investigate the residue depletion kinetics and establish the withdrawal period of fluralaner in chickens and eggs, a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantitative determination of fluralaner residues in edible chicken tissues and eggs. Furthere more, fifty healthy Hy-Line Brown laying hens were selected and received fluralaner solution via drinking water at a dosage of 0.5 mg/kg body weight on the 1st day and 8th day. At 7 days after the final administration, fluralaner residues in all edible tissues declined to levels below their respective maximum residue limits (MRLs). Using WT1.4 software and calculations based on the 95 % confidence interval, the withdrawal periods for fluralaner in muscle, liver, kidney, skin/fat were 12.19, 8.06 10.67 and 4.60 days, respectively. On day 7 after the final administration, the maximum observed fluralaner residue concentration in eggs was 890.72 µg/kg. This level was below the established MRL for eggs (1300 µg/kg) as stipulated by both the Ministry of Agriculture and Rural Affairs of China and the European Union. Moreover, the fluralaner concentration at each time point in eggs remained below 1300 µg/kg at 95 % confidence interval. Considering inter-individual variability, age related metabolic differences, and in reference to the approved withdrawal and egg-discard periods of the originator formulation Exzolt®, a withdrawal period of 14 days was established for the self-prepared fluralaner solution in chickens, while the egg-discard period was determined to be 0 days. Current study provides a scientific and regulatory basis for the rational use of fluralaner in laying hens and supports the establishment of an appropriate withdrawal period and egg-discard strategy in layer production systems.
Recurrent aphthous ulcers (RAU) is a common idiopathic oral mucosal disorder marked by painful, round ulcers on non-keratinized tissues such as the buccal, labial, and lingual mucosa. These recurrent lesions impair oral function and quality of life. However, systemic treatments, such as oral or injectable medications, often exhibit limited efficacy and are associated with notable adverse effects. The effectiveness of topical treatments is often limited by the barrier properties of the oral epithelium and the dynamic oral environment. Continuous salivary flow and mechanical forces from speaking and mastication dilute, remove, or prevent adequate absorption of locally applied drugs, contributing to inconsistent therapeutic outcomes. Biomedical microneedles offer a promising alternative for delivering drugs to the oral mucosa, overcoming many shortcomings of conventional topical, oral, and injectable methods. Their capacity to painlessly breach superficial barriers enhances drug bioavailability while minimizing discomfort, bleeding, and infection risk. These features collectively improve patient adherence and provide a more acceptable treatment modality for recurrent conditions such as RAU. With rapid advancements in microneedle materials, fabrication techniques, and drug-loading strategies, emerging microneedle-based delivery systems are increasingly adaptable to the unique environment of the oral cavity. These include superior mucosal adhesion to prevent detachment, sustained drug release for prolonged retention, penetration into the pseudomembrane to bypass physical barriers, and the potential for designing multifunctional and smart-responsive systems. Such characteristics render microneedle-based systems a more acceptable and effective approach for managing recurrent conditions like RAU. This review provides an updated framework for understanding the potential of innovative microneedle technologies in the management of recurrent aphthous ulcers and highlights future opportunities for clinical translation.
Swallowing and diaphragmatic functions share neural regulatory pathways and require synchronous assessment. Patients who have had a stroke are susceptible to many complications, of which dysphagia and diaphragmatic dysfunction are particularly common. To compare the distribution and severity of swallowing function in stroke patients with and without diaphragmatic dysfunction, and to explore the correlation between swallowing and diaphragmatic functions. This cross-sectional observational study among 102 Chinese stroke patients with hemiplegia was conducted in August 2022 to December 2024. Data collection was completed in the first 48 h following admission, including sex, age, post-stroke duration, stroke type, stroke region, hemiplegia side, nasogastric feeding, and pneumonia. The patients were stratified into two groups by the presence or absence of diaphragmatic dysfunction, which was assessed by diaphragmatic ultrasound with a threshold of diaphragm thickening fraction (TFdi) < 20%. We compared the distribution and severity of different swallowing functions using the Modified Barium Swallow Study Impairment Profile (MBSImP) and the Penetration-Aspiration Scale (PAS) by Videofluoroscopic Swallowing Study (VFSS) between the two groups. Significant differences were found between the two groups in the oral and pharyngeal phases of the MBSImP (p < 0.003), including hold position/tongue control, bolus preparation/mastication, bolus transport/lingual motion, oral residue, initiation of the pharyngeal swallow, anterior hyoid motion, pharyngeal stripping wave, and pharyngeal residue (p < 0.003). In contrast, there were no significant differences between the two groups in some components of the MBSImP including lip closure, soft palate elevation, laryngeal elevation, epiglottic movement, laryngeal closure, pharyngeal contraction, and tongue base retraction (p > 0.003). The severity of swallowing physiological impairment by MBSImP between the two groups, including the oral phase, pharyngeal phase and total MBSImP scores showed significant differences (p < 0.003). By contrast, the distribution and severity of penetration and aspiration risk by PAS showed no statistically significant difference between the two groups (p > 0.003). TFdi was negatively correlated with grades of Water Swallowing Test, the oral phase, pharyngeal phase and total MBSImP scores (rs = -0.327 to -0.300, p < 0.003). Whereas no significant correlations were found between TFdi and pneumonia, nasogastric feeding and the PAS scores (p > 0.003). Patients with diaphragmatic dysfunction exhibited a higher proportion of swallowing physiological impairment in the oral and pharyngeal phases, along with greater severity of such impairments. Diaphragmatic function was correlated with swallowing function, but the correlation was weak and of uncertain clinical significance.
Oleanolic acid (OA) is a natural anti-inflammatory triterpenoid. This study investigates its therapeutic potential against rheumatoid arthritis (RA), a chronic autoimmune condition characterized by inflammatory activity, and explores the novel mechanism of gut microbiota modulation in a rat model. The anti-arthritic effect of OA was assessed in collagen-induced arthritis (CIA) in rats following oral or intravenous administration. Arthritis severity, joint pathology, and mesenteric Th17/Treg cell frequencies were evaluated. The role of gut microbiota was investigated using 16S rRNA sequencing and antibiotic ablation. Oral, but not intravenous, OA administration significantly alleviated arthritis and joint damage in CIA rats, indicating a gastrointestinal-dependent mechanism. Therapeutically, oral OA modulated gut microbiota by reducing Prevotella abundance and restored immune balance by decreasing Th17 and increasing Treg cell frequencies. This protective effect was abolished by co-treatment with antibiotics, confirming gut microbiota-dependency. Taken together, our findings show that the improvement in CIA after oral administration of OA is mainly due to changes in the structure and function of the gut microbiota. This study, therefore, suggests that OA is a promising therapeutic candidate for RA, based on its ability to restore the intestinal microenvironment.
Flurbiprofen axetil, an ester prodrug of flurbiprofen, undergoes premature hydrolysis in the gastrointestinal tract, which induces mucosal damage and restricts its oral application. In this study, carboxylesterase 2 (CES2) was re-identified as the primary enzyme mediating this hydrolytic process. Using glycyrrhetinic acid derivative 13 (GA13) as a selective CES2 inhibitor, we assessed its effects on flurbiprofen pharmacokinetics, tissue distribution, efficacy, and toxicity following oral co-administration with flurbiprofen axetil in rats. GA13 potently inhibited flurbiprofen axetil hydrolysis in human and rat intestinal microsomes (IC50 = 1.8 μM and 4.8 μM, respectively) and moderately suppressed CYP2C9-mediated flurbiprofen metabolism in liver microsomes (IC50 = 8.91 μM and 13.27 μM, respectively). Oral co-administration of GA13 (20 mg/kg) significantly improved the pharmacokinetic profile of product flurbiprofen: the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased by 60 % and 85 %, respectively; the time to reach Cmax was doubled; and the half-life (t1/2) was prolonged by 30 %. Tissue distribution analyses revealed a 7-fold reduction in flurbiprofen levels in gastric tissue at 0.5 h post-administration, whereas its distribution in other organs remained unaltered. In the carrageenan-induced paw edema model, combination therapy with GA13 and flurbiprofen axetil exhibited enhanced anti-inflammatory efficacy compared to flurbiprofen axetil monotherapy. Importantly, 14-day repeated dosing showed that GA13 co-administration markedly attenuated gastrointestinal injury, preserved gastric prostaglandin E2 (PGE2) levels, and prevented weight loss. These beneficial effects were attributed to the reduction in local flurbiprofen generation mediated by CES2 inhibition. Collectively, this study demonstrates that selective CES2 inhibition by GA13 facilitates the effective oral delivery of flurbiprofen axetil, with improved bioavailability, enhanced therapeutic efficacy, and reduced gastrointestinal toxicity.
Diabetes is associated with a number of significant long-term effects. In this study we consider that purslane which possesses numerous of pharmacological properties, and metformin, an antidiabetic drug, may have a therapeutic effects on diabetes-induced memory impairments in rats. Forty male albino rats were randomly divided into five groups. Group I served as control group. The other four groups were first fed on HFD followed by a single interpretonial (i.p.) dose of STZ at a dose of (35) mg/kg then the groups were divided as following Group II diabetic group Group III, PEE group administered with oral dose of purslane ethanolic extract (100 mg/kg) for another four weeks. Group IV, MET group administered with oral dose of metformin (100 mg/kg) for another four weeks. Group V (PEE + MET) administered with oral dose of combination of both purslane ethanolic extract (50 mg/kg) and MET (50 mg/kg) for another four weeks. During the treatment rats were tested for memory and learning abilities (Morri's water maze test). Hippocampal samples were collected for biochemical, and histological measurements. Biochemical evaluation included (NO and TBARS) as an oxidative stress marker, (GSH, GPX, SOD, Catalase) as antioxidant, and inflammatory cytokines (tumor necrosis factor-α and interleukin-1β, interleukin-IL-6). Also, P-tau protein, (dopamine and GABA) as neurotransmitters, and for cholinergic system (acetylcholinesterase) were assessed, in addition to histological examinations of hippocampus. Diabetic rats showed a marked cognitive impairment in the Morris water maze test and alteration in the other biochemical and histological features. Intrestingly, PEE and MET treatments partially dramatically enhanced antioxidant levels. Also, reduced oxidative stress, pro-inflammatory mediators, and, phosphorylated tau levels. In addition, PEE and MET treatments partially modulated neurochemical profiles associated with memory function. The combined PEE + MET treatment showed the most pronounced improvement, reflecting synergistic effects. Individual data points highlighted consistent trends across animals. Also, it exhibited a significant restoration of normal hippocampal architecture, as confirmed by hematoxylin and eosin staining. The data obtained indicated that PEE, either alone or in combination with MET, has strong neuroprotective potential against STZ/HFD-induced diabetes. These safeguarding effects are probably because of its strong anti-inflammatory and antioxidant properties.
Maternal iron deficiency anemia (iron deficiency anemia) is a persistent global health challenge with increased risk of adverse perinatal outcomes. A recent multicenter clinical trial found reduced rates of low birthweight infants in mothers treated initially (early second trimester) with IV ferric carboxymaltose compared to oral iron. Secondary findings included improved hematologic indices 4 weeks post-treatment, as well as reduced rate of stillbirth with single dose IV iron infusion. We aimed to determine if the initial response to iron therapy was associated with risk of stillbirth and other adverse perinatal outcomes in pregnant singletons with moderate iron deficiency anemia STUDY DESIGN: This is a secondary analysis of a multi-center randomized controlled trial in India that compared single dose intravenous iron to oral iron for the initial management of moderate iron deficiency anemia (Hb 7.0-9.9g/dL) at 14-17 weeks gestation. The primary outcome for this secondary analysis is stillbirth. Secondary outcomes were early preterm birth <34 weeks, small for gestational age infants (<10%ile). The predictors of interest were maternal hemoglobin, ferritin, and transferrin saturation (TSAT), measured at 20-24 weeks gestation. Longitudinal hematologic and iron indices through pregnancy and association with outcomes were also assessed. Relative risk of each outcome based on post-treatment hemoglobin, ferritin, and TSAT was assessed with Poisson regression, adjusting for maternal age, BMI, parity, treatment modality, baseline Hb, and study site. Two-sided alpha=0.05 used for all analyses. Given that most nutrients exhibit U-shaped or threshold risk curves, we also fit models allowing for a quadratic function for the relationship between hematologic parameters at all times and risk of each event RESULTS: 4252 participants were included in this analysis, 1421, 1424, 1407 received intravenous ferric derisolmaltose, ferric carboxymaltose, and oral iron respectively. In evaluating the linear relationship, each unit of increasing Hb response at 20-24 weeks was significantly associated with reduced risk of stillbirth (RR 0.74 (0.56, 0.98). In evaluating the quadratic relationship, we found that there was a significantly progressively increased risk of stillbirth (p<0.0001) and early preterm birth< 34 weeks (p=0.01). Although there was a significant quadratic relationship identified with small for gestational age infant and Hb (p=0.008), the relative risk of SGA and lower Hb was not statistically significant. Inadequate improvement in hemoglobin at 20-24 weeks following iron therapy in pregnancies complicated by moderate iron deficiency anemia is associated with increased risk of stillbirth and early preterm birth. Our findings highlight the potential importance of early screening and treatment of maternal anemia,. Given the association between persistent anemia at 20-24 weeks and adverse outcome, prospective trials should focus on whether early pregnancy, or even preconception, improvement in hemoglobin is an effective intervention to prevent adverse perinatal outcomes such as stillbirth and early preterm birth.
Fast-track and outpatient surgery have significantly reduced postoperative hospital stays across many surgical specialties. As a result, patients are increasingly discharged with strong opioid prescriptions, contributing to the global opioid crisis. Careful follow-up and opioid tapering are essential. While multidisciplinary Transitional Pain Services (TPS), involving pain specialists, psychologists, and physiotherapists, have shown promise, their widespread implementation is limited by costs and complexity. To address these barriers, we implemented a nurse-led TPS, supervised by a pain specialist and embedded within a multidisciplinary pain clinic. The aim of this study was to evaluate its effectiveness in clinical practice, including a mechanism-based treatment approach to postsurgical pain aimed at opioid tapering and optimizing the use of adjuvant analgesics. This observational cohort study included postoperative patients discharged with >20 mg oral oxycodone equivalents and/or those experiencing or at risk for neuropathic pain. Referred patients received telephone consultations by a nurse practitioner (NP) one to two weeks post-discharge. Each consultation included assessment of pain severity, neuropathic characteristics (using the first two items of the DN4 questionnaire), current analgesic use, and willingness to taper opioids. Patient education and motivational interviewing techniques were employed to support opioid tapering. Descriptive statistics and paired t-tests were used to analyze the data. Between June 2019 and July 2025, 243 patients were enrolled in the TPS. Following nurse-led counseling, 73 % of patients discontinued opioid use entirely, 23 % significantly tapered their dosage (from mean 101-43 mg oral oxycodone equivalent), and 4 % continued at the same dose. Anti-neuropathic medications were initiated in 22 % of patients. A nurse-led Transitional Pain Service is a feasible and effective approach to support opioid tapering in postoperative patients. In addition, early screening for neuropathic pain allows for targeted treatment. This model offers a scalable alternative to traditional multidisciplinary TPS programs.
Bone defect repair presents a significant clinical challenge in oral and maxillofacial surgery and orthopedics. Implant-associated infection and insufficient osseointegration often compromise clinical outcomes, while traditional repair materials still struggle to simultaneously provide mechanical support, antibacterial activity, and osteogenic efficacy. This study employed magnetron sputtering to fabricate high-entropy nitride (HEN) coatings with varying silver (Ag) contents. Among these, the stable single-phase solid solution (TiZrNbHfTaAg)N coating with 5.7 at. percentage (at%) Ag exhibited outstanding comprehensive properties. This coating combines favorable biocompatibility with potent antibacterial activity, exhibiting antibacterial rates of 90.6% and 97.1% against common oral pathogens F. nucleatum and P. gingivalis, respectively. It also promotes osteoblast differentiation and mineralization by activating the MAPK/ERK signaling pathway, thereby upregulating the expression of genes and proteins associated with osteogenesis. In vivo validation using a rabbit tibia defect model showed that implantation of the (TiZrNbHfTaAg)N coating significantly improved indicators of bone regeneration and osseointegration strength. This coating offers a novel surface modification approach to address bone defect repair challenges through its "antibacterial-osteogenic" synergistic effect and bone regeneration mechanism mediated by the MAPK/ERK pathway, demonstrating considerable potential for clinical translation.
To investigate risk factors for early childhood caries (ECC) among 1-2-year-old children in Beijing and to assess the effect modification of baseline caries experience on the associations between other risk factors and subsequent caries outcomes. A 12-24-month prospective study was conducted from 2021 to 2023, a total of 919 participants with valid data were included in this study, with a follow-up rate of 76.9%. Oral health information and related factors were collected through parent-completed questionnaires and clinical dental examinations. Univariate analyses and a zero-inflated negative binomial (ZINB) regression model were used to identify risk factors. Caries incidence during follow-up was 29.8%, and the mean increase in decayed, missing, and filled primary teeth (Δdmft) was 0.94 ± 1.94. In the full-sample ZINB model, significant predictors of caries risk were frequency of snack intake, frequency of candy consumption, frequency of bedtime tooth brushing, frequency of bottle use at bedtime, and baseline caries status. In the baseline caries-free group, additional significant predictors of incident caries risk were parents' caries status, frequency of saliva-sharing behavior, frequency of post-meal mouth rinsing, and the presence of additives in daily drinking water. Interaction analyses showed that the effects of parents' caries status, saliva-sharing frequency, post-meal mouth rinsing frequency, presence of additives in daily drinking water, bedtime brushing frequency, and history of dental attendance on caries risk differed significantly between children with and without baseline caries. The risk of early childhood caries (ECC) among 1-2-year-old children in Beijing was associated with multiple oral health-related factors. Baseline caries experience was a strong predictor of subsequent caries risk and significantly modified the effects of other risk factors.
Danshensu (DSS) is one of the water-soluble components extractable from the traditional Chinese medicine Salvia miltiorrhiza Bge., exhibiting pharmacological effects such as promoting blood circulation, dilating coronary arteries, and improving cerebral blood flow. The Danshensu derivative (OZD-1) obtained through the derivatization of DSS is a potential multi-target drug for the central nervous system, however, its mechanism of action against cerebral ischemia-reperfusion injury (CIRI) remains unclear. Systematically investigating the therapeutic potential and mechanisms of action of Danshensu derivative against cerebral ischemia-reperfusion injury. Rat brain microvascular endothelial cells (RBMVECs) were cultured in vitro to establish an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model. Groups included a control group, an OGD/R model group, and OZD-1 low-dose (12.5 μmol/L), medium-dose (25 μmol/L), and high-dose (50 μmol/L) groups. Cell viability, migration capacity, and vascular lumen formation were assessed using the CCK-8 assay, cell scratch assay, and matrigel matrix gel assay, respectively. In vivo, a transient middle cerebral artery occlusion (tMCAO) model was established in rats. Animals were randomly divided into the sham, model, OZD-1 (35, 70, 140 mg/kg), Edaravone (Eda), and DSS groups. Daily oral administration was performed post-surgery for 14 consecutive days. Tissue pathology staining, behavioral tests, and regional cerebral blood flow imaging assessed brain tissue damage, cognitive function, and ischemic side cerebral blood flow recovery, respectively. Transcriptome sequencing analyzed differential gene expression and pathway enrichment patterns. Western blot detection measured expression levels of proteins related to the PI3K-AKT-CREB signaling pathway, phosphoproteins, downstream apoptosis-related proteins, and CD31, CD34, and VEGFA proteins. In vitro experiments demonstrated that OZD-1 dose-dependently enhanced the viability of RBMVECs following OGD/R injury, significantly improving cell migration and luminal formation capabilities. In vivo studies revealed that compared to the model group, rats in all OZD-1 dosage groups exhibited markedly improved cognitive function, significantly restored cerebral blood flow in the ischemic hemisphere, and substantially reduced pathological brain tissue damage. Transcriptome sequencing results indicated significant enrichment of genes associated with the PI3K-AKT signaling pathway following OZD-1 intervention. Western blot experiments confirmed that OZD-1 significantly upregulates the phosphorylation levels of proteins related to the PI3K-AKT-CREB signaling pathway in OGD/R-injured cells and brain tissue from tMCAO rats, thereby promoting VEGFA-mediated angiogenesis and inhibiting apoptosis. To further verify pathway involvement, in vitro inhibition experiments were performed in RBMVECs using the PI3K inhibitor LY294002 and CREB inhibitor 666-15. These inhibitors abolished the OZD-1-induced upregulation of p-PI3K, p-AKT, and p-CREB, and reversed its protective effects on cell viability, migration, and tube formation. These results confirm that OZD-1 protects vascular endothelial cells directly via activating the PI3K-AKT-CREB pathway. OZD-1 exhibits significant neuroprotective effects against CIRI in rats, improving cognitive function, promoting vascular regeneration in ischemic areas, repairing damaged RBMVECs, and reducing apoptosis. Its mechanism of action is associated with the activation of the PI3K-AKT-CREB-VEGFA signaling pathway.
Gout is a prevalent inflammatory arthritic disorder affecting more than 40 million people worldwide, with incidence increasing due to aging populations, lifestyle factors, and metabolic comorbidities. Febuxostat (FEB), a xanthine oxidase inhibitor used for urate-lowering therapy, often triggers acute gout flares during treatment initiation, necessitating concurrent anti-inflammatory therapy such as aceclofenac (ACE). However, the oral administration of both drugs is associated with poor aqueous solubility, first-pass metabolism, and gastrointestinal adverse effects. The present study aimed to develop and optimize a ufasome-based transdermal gel co-loaded with FEB and ACE to provide controlled and sustained drug release for improved gout management. Ufasomes were prepared using the thin-film hydration method and optimized through a Box-Behnken design. The optimized formulation exhibited nanosized vesicles (199 nm for FEB and 365 nm for ACE), high entrapment efficiency (> 80%), and stable zeta potential values. The ufasomal gel demonstrated sustained in vitro drug release over 24 h compared with plain drug gel, while ex vivo permeation studies indicated controlled diffusion across rat skin, suggesting formation of a drug reservoir within cutaneous layers. The drug release follows 1st order model for FEB and ACE. In vivo pharmacodynamic studies showed significant reductions in serum uric acid levels (p < 0.01) and paw edema volume (p < 0.001). These findings suggest that the FEB-ACE ufasomal transdermal gel offers a sustained delivery platform that may improve therapeutic outcomes and patient compliance in gout therapy. The novelty of this work lies in the dual-drug ufasomal transdermal system integrating urate-lowering and anti-inflammatory therapy in a single formulation, offering a potential alternative to conventional oral treatment for gout management with improved therapeutic convenience.
This article  examines the sexual and reproductive health experiences of eight people who migrated to London in the late twentieth century from Kenya, Zambia, Nigeria, Sudan, and Uganda. Their experiences were captured through an oral history partnership with NAZ, a sexual health charity run by and for racialized people in London. They illuminate the informal processes of sexual and reproductive health knowledge production before migrating to London, such as jokes and gossip, in the face of minimal formal education on these topics. All of the interviewees studied in this article are living with human immunodeficiency virus (HIV)  and moved to London in their early twenties. In this article, we pay close attention to their experiences of sexual and reproductive health services and HIV and acquired immunodeficiency syndrome (AIDS), which provide novel understandings of the ways in which such services were experienced by those who migrated to London. By listening attentively to the interviews and deploying oral history theories around memory and narrative, we argue that migration and the generational shifts of the interviewees acted as major turning points in their sexual and reproductive health journeys by increasing exposure to such services. While often empowering, such encounters were, at times, also experienced as alienating or racist. In addition, the interviews reveal how British public health campaigns resonated internationally and were closely entangled in migration narratives. The interviewees' experiences of HIV/AIDS demonstrate the multiplicity of HIV/AIDS histories, offering new perspectives on HIV/AIDS experiences in Britain.