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.

AIM: To investigate the mechanism of Hexue Mingmu Tablets(HXMMT)in improving diabetic retinopathy(DR)based on transcriptomics.METHODS: Zebrafish DR models were established by 3-day glucose induction(130 mmol/L)starting at 3 days post-fertilization(dpf). Larvae were randomized into four groups: control group(CG; aquaculture water), model group(MG; 130 mmol/L glucose), low-dose HXMMT treatment group(L-HX; 130 mmol/L glucose +7.5 mg/L HXMMT), and high-dose HXMMT treatment group(H-HX; 130 mmol/L glucose +75 mg/L HXMMT), with a 3-day intervention period until 6 dpf. The area and length of eyes, and body length of zebrafish were observed by stereomicroscopy, retinal morphology was observed by hematoxylin-eosin staining(HE), and retinal vessel diameter was observed under fluorescence microscope. Differentially expressed genes(DEGs)were identified by RNA-sequencing(RNA-seq)technology to further elucidate the molecular mechanism of HXMMT in improving DR in zebrafish, and the sequencing accuracy was validated through quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS: HE staining demonstrated that the intervention with HXMMT significantly improved the disordered cell arrangement, widened gaps, and thickened inner nuclear layer(INL)in ganglion cell layer GCL); retinal vascular diameter quantification revealed that the retinal vessel diameter of the MG significantly increased compared with the CG, and it was significantly changed after the intervention of HXMMT, with significant efficacy in the H-HX(P<0.05); transcriptomics profiling identified 1 470 reversed DEGs, predominantly enriched in the AMPK signaling pathway, FoxO signaling pathway, retinal developmental processes, and tight junction regulation. Technical validation confirmed strong correlation between qRT-PCR and RNA-seq data(R2=0.8571, P<0.05).CONCLUSION: HXMMT may improve retinal vascular microcirculation disorders in DR by regulating core targets including vsx1, pde6c, arr3a, plk1, fbp1b, foxo1a, pcna, and cdk1, as well as synergistically modulating processes such as retinal development in camera-type eyes, visual perception, microtubule cytoskeletal organization, tight junctions, and the AMPK signaling pathway, Foxo signaling pathway.

OBJECTIVE: To observe the effect of Guilu Taohong Formula on semen quality in varicocele (VC) models of rats, and to explore its possible mechanism. METHODS: Forty-eight male SD rats were randomly divided into four groups (sham group, model group, Guilu Taohong Formula group and L-carnitine group). After the establishment of models, the rats were treated with intragastric administration for eight consecutive weeks. The general condition of the rats was observed. After the gavage, the testicular and epididymal indices were calculated. Semen quality was assessed using an automatic semen analyzer. Apoptosis of testicular cells was assessed by TUNEL staining. And the expression levels of B-cell lymphocytoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine aspartate protease-3 (caspase-3) in testicular tissue were detected by Western blot. RESULTS: Compared with the sham group, testicular index, epididymal index, sperm concentration, the percentage of progressive motility of sperm (PR%) and the expression level of Bcl-2 decreased in model group(P<0.01). An increased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were observed in model group as well(P<0.01). Compared with the model group, the testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 in Guilu Taohong Formula group increased significantly (P<0.05, P<0.01). A decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were detected in Guilu Taohong Formula group as well(P<0.01). Similarly, the L-carnitine group showed increased testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 protein (P<0.05, P<0.01), where showed decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins compared with model group (P<0.01, P<0.05). CONCLUSION Guilu Taohong Formula improves semen quality in VC model rats and reduces the apoptosis rate of spermatogenic cells in testicular tissue, which may be related to the promotion of Bcl-2 protein expression and the inhibition of Bax and caspase-3 protein expression levels.
Male ; Animals ; Varicocele/drug therapy* ; Rats ; Apoptosis/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Semen Analysis ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal ; Spermatozoa/drug effects* ; Testis/drug effects*

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

Objective:To explore the feasibility of endoscopic-assisted resection of congenital first and second branchial cleft malformations in children via the external fistula incision approach. Methods:A retrospective analysis was conducted on 20 children with congenital first and second branchial cleft malformations who were admitted to the Department of Otolaryngology Head and Neck Surgery of Hu'nan Children's Hospital from January 2020 to January 2024 and whose families voluntarily consented to endoscopic surgery. Clinical data were collected. There were 12 males and 8 females, aged from 10 months to 12 years. The surgical methods and experiences of endoscopic-assisted resection of congenital first and second branchial cleft malformations in children via the external fistula incision approach were summarized. Results:All 20 children underwent endoscopic-assisted resection of congenital first and second branchial cleft malformations via the external fistula incision approach. For children with second branchial cleft malformations whose internal fistula openings were located on the pharyngeal arch mucosa or palatine tonsils, the tonsils were preserved, the internal fistula openings were ligated at a high position, the fistula tubes were removed, and the residual ends were cauterized with bipolar electrocoagulation to destroy the residual fistula epithelial cells. There were no obvious complications after the operation. During the 12-month follow-up, no recurrence of the fistula tubeswas observed, and the recovery was good. Conclusion:Congenital first and second branchial cleft fistulas in children are rare, and surgical resection is the preferred treatment method. The endoscopic-assisted resection of congenital first and second branchial cleft malformations in children via the fistula incision approach offers a clear surgical field, an ideal cosmetic effect, and a satisfactory curative effect.
Humans ; Female ; Male ; Branchial Region/surgery* ; Retrospective Studies ; Child ; Infant ; Child, Preschool ; Endoscopy/methods* ; Fistula/surgery* ; Craniofacial Abnormalities/surgery* ; Treatment Outcome ; Pharyngeal Diseases

ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

Objective: To investigate the relationship between serum alanine transaminase (ALT) and carotid intima media thickness (cIMT) in adolescents, providing evidence for early prevention and control strategies for cardiovascular structural abnormalities in adolescents. Methods: Data were obtained from the third follow up survey (from October to November 2023) of the "Huantai Children Cardiovascular Health Cohort", including 1 153 healthy adolescents with complete information. Analysis of variance (ANOVA) was used to compare cIMT across different ALT level groups, and multiple linear regression was employed to analyze the relationship between serum ALT levels and cIMT. Results: Significant differences in cIMT were observed among Q 1, Q 2, and Q 3 ALT level groups [(0.56±0.04) (0.57±0.04) (0.59±0.04)mm, respectively; F=3.61, P <0.01]. After adjusting for covariates, multiple linear regression revealed a positive correlation between ALT levels and cIMT ( β=0.18, P <0.01). Gender subgroup analysis showed similar results in males ( β=0.19, P <0.01), but no statistically significant association was found in females ( β=0.07, P = 0.54). Conclusions Elevated serum ALT levels are associated with an increased risk of vascular structural damage in adolescents, especially in boys. Early detection and control of abnormal serum ALT levels can help to reduce early vascular structural damage and further reduce the risk of adverse cardiovascular events.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.