Background: Type 2 diabetes mellitus (T2DM) is a complex, multifactorial disease with a significant global burden. Although genome-wide association studies (GWAS) have identified many T2DM-associated variants, most lie in non-coding regions, making it difficult to interpret their functional roles. Methods: We aimed to identify genetically regulated Cytosine–phosphate–Guanine (CpG) sites associated with T2DM by conducting a methylome-wide association study (MWAS), followed by Mendelian randomization (MR) and functional validation using human pancreatic cells and mouse models. MWAS was performed using summary statistics from large-scale GWAS and a DNA methylation (DNAm) prediction model to test associations between genetically predicted DNAm and T2DM. Results: We identified 111 CpG sites significantly associated with T2DM in Europeans, including 8 novel sites near genes not previously linked to T2DM. These findings were replicated in independent datasets. Many CpGs also showed associations with cardiometabolic traits, highlighting shared epigenetic mechanisms. Trans-ethnic MR analysis confirmed consistent effects for six CpGs in East Asians. Functional analysis revealed that several CpGs regulate gene expression in human pancreatic α- and β-cells. Among them, 2´-5´-oligoadenylate synthetase like (OASL) expression, regulated by a significant CpG, was differentially expressed in α-cells of T2DM cases compared to controls. Supporting evidence from mouse models suggests a role for OASL in glucose regulation. Conclusion Our study identifies novel genetically regulated CpG sites associated with T2DM risk and highlights OASL as a potential epigenetic regulator of glucose metabolism in α-cells. These findings provide mechanistic insights into the epigenetic architecture of T2DM and suggest potential targets for cross-ethnic biomarker development and therapeutic intervention.

Processed electroencephalogram (EEG) indices, such as the Bispectral Index, have markedly influenced anesthesia practice as they translate brain activity into simple numerical indices. Nevertheless, as the manufacturing algorithms are not disclosed, the underlying neurophysiology remains obscured. Additionally, these indices are often affected by electromyographic contamination, pharmacological variability, and patient-specific EEG heterogeneity. In contrast, an EEG spectrogram, or density spectral array, preserves the frequency- and time-resolved structures of cortical oscillations. This information is presented in a form that is both physiologically meaningful and clinically interpretable. In this review, we trace the evolution of anesthesia from an index-based to a spectrogram-guided approach, and summarize the clinical rationale for adopting the latter. Key applications of this approach include the use of frontal alpha power as a biomarker of cortical stability and postoperative brain health, the identification of nociceptive arousal through alpha dropout and beta or delta arousal patterns, and individualized titration of multimodal or age-specific anesthetic management. Although current devices lack standardized quantitative alpha metrics and have limited sensitivity for low-frequency brain wave components, structured EEG education programs have proven to be effective in terms of fostering spectrogram literacy among anesthesiologists. By combining neurophysiological precision with bedside practicality, the EEG spectrogram represents a pivotal advance toward individualized, mechanism-based, and brain-protective anesthesia, transforming anesthetic monitoring from mere algorithmic abstraction to cortical insight.

Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.

Objective To investigate the effects of ischemia time and storage periods on RNA quality in fresh-frozen breast cancer(BC)and esophageal cancer(EC)tissue samples in order to establish evidence-based protocols for biobank sample management.Methods The tumor(T)and paired normal(N)tissue samples from 6 cases of BC and 6 cases of EC were collected and cryopreserved in Biobank,Shantou Central Hospital.Mirror paraffin-embedded tissues were simultaneously prepared into sections for morphological analysis.The samples were divided into two groups of<15 min and 15-30 min according to ischemia time,and RNA quality was analyzed at 4 storage periods of 8-10 months(T1),14-16 months(T2),26-28 months(T3)and 38-40 months(T4).Results In 96 analyzed samples,93.8%(90/96)exhibited high quality(RIN≥6),with 89.6%(43/48)in BC and 97.9%(47/48)in EC.Significant differences in RIN were observed between BC group and EC group(8.050 vs.8.600,P=0.009).In EC group,RIN value was significantly negatively correlated with RNA yield(P<0.001).Moreover,RIN values of tumor-normal pairs exhibited markedly significant differences(7.550 vs.9.000,P<0.001).In contrast,no significant difference was detected in BC group(8.200 vs.7.700,P=0.348).Statistical analysis showed that RIN value was positively correlated with 28S/18S(P<0.001),but had no correlation with tumor content(P=0.676)and necrotic content(P=0.055).Neither ischemia time(<15 min vs.15-30 min:8.200 vs.8.300,P=0.932)nor storage periods(T1-T4:8.400,7.700,8.450,8.600,P=0.163)compromised RNA quality.Conclusion Organ origin and tissue type could influence RNA quality of fresh-frozen tissue samples.However,limited ischemia time(≤30 min)and long-term storage period(38-40 months)do not adversely affect RNA quality in fresh-frozen breast cancer and esophageal cancer tissue samples.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

Microplastics are widely present in various environments such as water bodies,land,and atmosphere,which pose threats to the ecological environment and human health through transmission and accumulation in the food chain.The existing detection techniques for microplastics face challenges such as complex preparation procedure of samples,low efficiency in processing large batches of samples,and difficulties in handling complex samples.Therefore,there is an urgent need for rapid and efficient detection techniques suitable for complex microplastics samples in the field of environmental monitoring.Raman spectroscopy,known for its advantages such as rapidity,accuracy,high sensitivity,non-destructiveness,and non-contact,demonstrates great application potential in detection of microplastics.Deep learning,an artificial intelligence method known for its large-scale data processing,nonlinear modeling and automatic feature extraction capabilities,is receiving increasing attention in the analysis of Raman spectroscopy signals.The application of deep learning-based Raman spectroscopy has significantly improved performance indicators such as detection efficiency and accuracy.This article introduced the existing Raman enhancement techniques,summarized the deep learning methods applied in Raman spectroscopy signal analysis,reviewed the recent research and application progress of deep learning-based Raman spectroscopy in detection of microplastics,and finally discussed the challenges and future prospects of deep learning-based Raman spectroscopy in detection of microplastics.

Objective: To retrospectively compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) with parotidectomy for superficial pleomorphic adenoma (PA). Materials and Methods: From March 2022 to October 2023, 88 patients diagnosed with superficial parotid PA underwent either RFA (n = 12; mean age, 47.1 years) or parotidectomy (n = 76; mean age, 47.8 years). Patients in the RFA group were matched to those in the surgery group in a 1:1 ratio using propensity scores based on age, sex, tumor volume, diameter, location, and comorbidities. Ultrasound characteristics, cosmetic scores (0–4), numerical rating scale scores (0–10), and complications were assessed before the procedures and at 1-, 3-, and 6-month follow-ups. Outcomes were compared between baseline and follow-up in the RFA group and between the RFA and surgery groups. Results: In the RFA group, significant reductions in tumor volume were observed between baseline (median, 2.02 cm 3 ) and the 1-month follow-up (median, 1.21 cm 3 ; P = 0.015), between the 1-month and 3-month follow-ups (median, 0.53 cm 3 ; P= 0.002), and between the 3- and 6-month follow-ups (median, 0.23 cm 3 ; P = 0.003). The volume reduction ratios at 1, 3, and 6 months were 39.7%, 79.9%, and 88.0%, respectively. The cosmetic score was significantly lower at 3- and 6-month followup compared to baseline (median 1 and 1 vs. 4, P = 0.04). The numerical rating scale scores did not differ significantly from baseline throughout follow-up. In the propensity score-matched analysis (12 patients per group), RFA was associated with a shorter median procedure time (61.5 vs. 253.3 minutes; P < 0.001), shorter hospital stay (0 vs. 4 days; P < 0.001), and lower cost (1859.9 vs. 3512.4 USD; P < 0.001) than parotidectomy, with no significant difference in overall complication rates (33.3% [4/12] vs. 41.7% [5/12]; P = 1.000). Conclusion RFA may be a safe and effective alternative to surgery for superficial parotid PA, offering a shorter median procedure time, shorter hospital stay, and lower costs.

Objective: To retrospectively compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) with parotidectomy for superficial pleomorphic adenoma (PA). Materials and Methods: From March 2022 to October 2023, 88 patients diagnosed with superficial parotid PA underwent either RFA (n = 12; mean age, 47.1 years) or parotidectomy (n = 76; mean age, 47.8 years). Patients in the RFA group were matched to those in the surgery group in a 1:1 ratio using propensity scores based on age, sex, tumor volume, diameter, location, and comorbidities. Ultrasound characteristics, cosmetic scores (0–4), numerical rating scale scores (0–10), and complications were assessed before the procedures and at 1-, 3-, and 6-month follow-ups. Outcomes were compared between baseline and follow-up in the RFA group and between the RFA and surgery groups. Results: In the RFA group, significant reductions in tumor volume were observed between baseline (median, 2.02 cm 3 ) and the 1-month follow-up (median, 1.21 cm 3 ; P = 0.015), between the 1-month and 3-month follow-ups (median, 0.53 cm 3 ; P= 0.002), and between the 3- and 6-month follow-ups (median, 0.23 cm 3 ; P = 0.003). The volume reduction ratios at 1, 3, and 6 months were 39.7%, 79.9%, and 88.0%, respectively. The cosmetic score was significantly lower at 3- and 6-month followup compared to baseline (median 1 and 1 vs. 4, P = 0.04). The numerical rating scale scores did not differ significantly from baseline throughout follow-up. In the propensity score-matched analysis (12 patients per group), RFA was associated with a shorter median procedure time (61.5 vs. 253.3 minutes; P < 0.001), shorter hospital stay (0 vs. 4 days; P < 0.001), and lower cost (1859.9 vs. 3512.4 USD; P < 0.001) than parotidectomy, with no significant difference in overall complication rates (33.3% [4/12] vs. 41.7% [5/12]; P = 1.000). Conclusion RFA may be a safe and effective alternative to surgery for superficial parotid PA, offering a shorter median procedure time, shorter hospital stay, and lower costs.

Objective: To retrospectively compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) with parotidectomy for superficial pleomorphic adenoma (PA). Materials and Methods: From March 2022 to October 2023, 88 patients diagnosed with superficial parotid PA underwent either RFA (n = 12; mean age, 47.1 years) or parotidectomy (n = 76; mean age, 47.8 years). Patients in the RFA group were matched to those in the surgery group in a 1:1 ratio using propensity scores based on age, sex, tumor volume, diameter, location, and comorbidities. Ultrasound characteristics, cosmetic scores (0–4), numerical rating scale scores (0–10), and complications were assessed before the procedures and at 1-, 3-, and 6-month follow-ups. Outcomes were compared between baseline and follow-up in the RFA group and between the RFA and surgery groups. Results: In the RFA group, significant reductions in tumor volume were observed between baseline (median, 2.02 cm 3 ) and the 1-month follow-up (median, 1.21 cm 3 ; P = 0.015), between the 1-month and 3-month follow-ups (median, 0.53 cm 3 ; P= 0.002), and between the 3- and 6-month follow-ups (median, 0.23 cm 3 ; P = 0.003). The volume reduction ratios at 1, 3, and 6 months were 39.7%, 79.9%, and 88.0%, respectively. The cosmetic score was significantly lower at 3- and 6-month followup compared to baseline (median 1 and 1 vs. 4, P = 0.04). The numerical rating scale scores did not differ significantly from baseline throughout follow-up. In the propensity score-matched analysis (12 patients per group), RFA was associated with a shorter median procedure time (61.5 vs. 253.3 minutes; P < 0.001), shorter hospital stay (0 vs. 4 days; P < 0.001), and lower cost (1859.9 vs. 3512.4 USD; P < 0.001) than parotidectomy, with no significant difference in overall complication rates (33.3% [4/12] vs. 41.7% [5/12]; P = 1.000). Conclusion RFA may be a safe and effective alternative to surgery for superficial parotid PA, offering a shorter median procedure time, shorter hospital stay, and lower costs.