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.

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

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.

Objective To observe the clinical efficacy of Yinlian Gargle in the treatment of acute radiation-induced oropharyngeal mucositis after nasopharyngeal carcinoma radiotherapy.Methods Thirty-two patients with nasopharyngeal carcinoma,who had received first radiation,were randomly split into two groups:the trial group(19 cases)and the control group(13 cases).After all groups were treated with radiotherapy and chemotherapy,the control group was given rinse treatment with saline whereas the trial group was given Yinlian Gargle.The incidence of severe acute radiation-induced oropharyngeal mucositis,the duration and intensity of oropharyngeal discomfort and pain(NRS score),quality of life(QOL-NPC score),duration and intensity of radiation-induced side effects(SE-QOL-NPC score)and symptoms of dry mouth(SE1 score)were monitored before and after intervention in two groups.Results The incidence of grade Ⅲ or above radiation-induced oropharyngeal mucositis until the sixth week of radiotherapy in the trial group was considerably lower than that in the control group(P＜0.001),while the incidence of grade I or above radiation-induced oropharyngeal mucositis at 1 month after radiotherapy in the trial group was obviously lower than that in the control group(P＜0.001).The NRS score of pharyngeal discomfort of the trial group was lower than that of the control group starting from the second week of radiotherapy(P＜0.05).The NRS score of oral and oropharyngeal pain was lower than that of the control group starting from the fourth week of radiotherapy(P＜0.05).The SE1 score of the trial group was higher than that of the control group starting from the fifth week of radiotherapy(P＜0.05).After one month of the completion of the radiotherapy,the NRS score of pharyngeal discomfort and the NRS score of oral and oropharyngeal pain in the trial group were lower than those of the control group(P＜0.001).The QOL-NPC score,SE-QOL-NPC score,and SE1 score were all higher than those in the control group(P = 0.05 or P＜0.05).Conclusion Patients with nasopharyngeal cancer can greatly reduce their risk of developing severe acute radiation-induced oropharyngeal mucositis,effectively delay and relieve related symptoms,and enhance quality of life by consistently using Yinlian Gargle during radiotherapy.Additionally,a month after the completion of radiotherapy,it still has positive therapeutic effects on acute radiation-induced oropharyngeal mucositis.

Objective To investigate the serum levels of C-C motif chemokine ligand 25(CCL25)and human Parkinson's disease protein 7(PARK7)in patients with sepsis and their relationship with acute lung injury(ALI).Methods 138 sepsis patients diagnosed and treated in Hefei Jingdongfang Hospital from February 2019 to February 2023 were selected as sepsis group.They were divided into ALI group(n=40)and non-ALI group(n=98)based on whether ALI occurred.70 healthy individuals who underwent physical examinations at the same time were taken as a control group.Enzyme linked immunosorbent assay was used to detect serum levels of CCL25 and PARK7.The correlation between serum CCL25,PARK7 and clinical indicators were analyzed by Pearson correlation analysis.Risk factors for secondary ALI in sepsis were conducted by multivariate logistic regression analysis.The value of serum CCL25 and PARK7 levels in predicting secondary ALI in sepsis were conducted by the receiver operating characteristic curve.Results Serum CCL25(367.52±46.87ng/L)and PARK7(54.26±17.45μg/L)in patients with sepsis was higher than that of the control group(48.17±5.26ng/L,12.31±4.12 μg/L),and the differences were statistically significant(t=46.825,19.813,all P＜0.05).ALI group patients CCL25(434.65±52.87ng/L vs 340.12±42.64ng/L),PARK7(103.47±22.51μg/L vs 34.18±7.46 μg/L),respiratory index(1.58±0.48 vs 0.88±0.07),PaCO2(50.11±6.27mmHg vs 40.42±5.20mmHg),APACHE Ⅱ score(23.37±3.82 point vs 17.15±3.41 point)and SOFA score(13.56±2.93 point vs 10.18±2.81 point)were all higher in the non-ALI group,while oxygenation index(237.14±23.56 point vs 341.14±21.37 point)and PaO2(55.87±8.03mmHg vs 63.11±7.14mmHg)were lower in the non-ALI group,and the differences were statistically significant(t=10.998,27.151,14.145,9.342,9.385,6.332,25.172,5.210,all P＜0.05).The serum levels of CCL25 and PARK7 in ALI patients were positively correlated with APACHE II score,SOFA score,respiratory index and PaCO2(r=0.579～0.801,all P＜0.05),while negatively correlated with oxygenation index and PaO2(r=-0.687,-0.643;-0.654,-0.712,all P＜0.05).Serum CCL25(OR=1.309,95%CI:1.040～1.646),PARK7(OR=1.288,95%CI:1.016～1.633),APACHE II score(OR=1.188,95%CI:1.019～1.384)and SOFA score(OR=1.197,95%CI:1.006～1.425)were independent risk factors for secondary ALI in sepsis patients.The area under the curve(95%CI)of the combination of serum CCL25 and PARK7 for predicting secondary ALI in sepsis was 0.833(0.784～0.872),which was greater than the individual indicators 0.770(0.725～0.835)and 0.741(0.691～0.790),and the differences were statistically significant(Z=4.602,4.318,P＜0.05).Conclusion Elevated serum levels of CCL25 and PARK7 in patients with sepsis are independent risk factors affecting the occurrence of secondary ALI in sepsis.The combination of the two has high predictive value for secondary ALI in sepsis.

Objective:To determine the correlation between the radiologic magnetic resonance imaging(MRI)depth of invasion(MRI-DOI)and pathologic depth of invasion(p-DOI)in oral cavity primary tongue squamous cell carcinoma(TSCC).Methods:Fifty-two cases of patho-logically proven primary TSCC were selected from patients admitted to The Ninth People's Hospital Affiliated to Shanghai Jiao Tong Uni-versity School of Medicine between January 2015 and December 2018.The p-DOI was measured,and the relationship between p-DOI and patients'clinicopathological parameters and prognosis were analyzed.The MRI-DOI was retrospectively measured,and the correlation between MRI-DOI and p-DOI was investigated.Results:Among the 52 patients,the average p-DOI was(8.5±5.5)(1-30)mm.p-DOI was signi-ficantly correlated with tumor size(P=0.021)and tumor site(P=0.047)when p-DOI was>5 mm,and significantly correlated with level Ⅲ lymph node metastasis(P=0.01)when p-DOI was≥10 mm.A close relationship between p-DOI>7 mm and the patient 5-year survival was also demonstrated(P=0.048).The average MRI-DOI was(10.3±4.3)mm,with a maximum of 19.9 mm and a minimum of 3.1 mm.The MRI-DOI≥10 mm also predicted poor survival in patients with TSCC(P=0.043).The MRI-DOI measured was generally slightly higher than p-DOI,with an average difference of 1.94 mm,and a strong correlation was found between MRI-DOI and p-DOI(r=0.831,P<0.001).Conclusions:MRI-based radiologic DOI measurement was useful in estimating postoperative p-DOI,and may help predict the depth of invasion of tumors preoperatively,which has important reference value for treating primary TSCC.

Objective:To investigate the effect of GRIM-19 on the resistance of carcinoma cells to the chemotherapeutic agent docetaxel in the treatment of PCa.Methods:Using siRNA technology to interfere with the gene expression in PCa cells,we estab-lished a model of GRIM-19 overexpression/knockdown in PCa cells.We investigated the effect of different expression levels of GRIM-19 on docetaxel-induced death of the PCa cells by qPCR,Western blot and flow cytometry,and assessed the value of GRIM-19 in re-ducing the chemotherapy-resistance of PCa cells.Results:GRIM-19 was down-regulated in PCa tissues and cells.Knockout of GRIM-19 significantly decreased the expression of siGRIM19 in the PC-3 and LNCaP cells,and reduced their death rate when treated with docetaxel compared with the control group.The expressions of GRIM-19 mRNA and protein were remarkably upregulated after transfection with GRIM-19,and the overexpressed GRIM-19 promoted the death of the PC-3 and LNCaP cells treated with docetaxel in a dose-dependent manner.Flow cytometry analysis showed a lower apoptosis rate of PC-3-R cells than that of PC-3 cells at different time points of docetaxel-induction at different doses.Conclusion:GRIM-19 is a PCa suppressor gene with a significant facilitating effect on the apoptosis of PCa cells,and the overexpression of GRIM-19 promotes docetaxel-induced PCa cell death and improves the sensitivity of chemotherapy.

A 49-year-old female examinee, employed at a paper company in Guigang, Guangxi (engaged in the production of napkins), visited the Qintang District People′s Hospital in Guigang on June 11, 2023, to apply for a health certificate. Salmonella was isolated during a physical examination screening for enteric pathogens ( Salmonella, Shigella), and repeated use of empirical antibacterial drugs failed to eradicate the pathogen. A reference laboratory identified the two isolates as S. Kentucky ST198 by performing serotyping, drug resistance phenotyping, and whole genome sequencing. Based on the regional serotype database of Salmonella in China, a phylogenetic tree of S. Kentucky ST198 resistance genotypes was constructed, defining both isolated strains as high-level drug-resistant ST198.2-1 subclade clones. Following a multidisciplinary consultation and based on antimicrobial susceptibility test results, the treatment was adjusted to amoxicillin/clavulanate and azithromycin. On August 19, three consecutive negative test results confirmed the eradication of Salmonella Kentucky.

The methanol extract of Huperzia serrata was separated and purified by ODS, AB-8 macroporous adsorption resin, dextran gel Sephadex LH-20 and silica gel column chromatography combined with the semi-pre HPLC. The chemical structures of the isolated compounds were identified by MS, IR, NMR, etc. Four compounds were isolated from Huperzia serrata and identified, named as serratinine C (1), lycobeline C (2), diphaladin A (3) and crenatine (4). Compound 1 is a new alkaloid, compounds 2-4 were isolated for the first time. In vitro biological activity experiments showed that compound 1 could significantly reduce the levels of nitric oxide and reactive oxygen species in glial cells induced by lipopolysaccharide and had significant antioxidant biological activity.

Curettage is the main treatment method for oral maxillofacial cystic lesions,but simple curettage may easily damage surrounding structures such as adjacent teeth and nerves,leading to incomplete removal of the cyst and large jaw defects.The curettage assisted by endoscopy can provide a good surgical field for the surgeons,can clearly identify the important anatomical structure during the operation and can remove the cyst wall tissue as much as possible,thereby reducing the damage and reducing the recurrence rate of the lesion.This article combines the characteristics of maxillofacial surgery with clinical treatment experience,summarizes relevant literature from both domestic and international sources,and engages in discussions with experts in order to provide reference for the clinical treatment of jaw cystic lesions with endo-scope assisted curettage.