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*

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.

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.

Objective To evaluate the clinical effect of Xuefu Zhuyu decoction combined with western medicine on elderly patients with refractory hypertension.Methods A total of 120 elderly patients with refractory hypertension were randomly divided into treatment group (n =60) and control group (n =60).Control group was given propranolol 5-10 mg orally,tid or qid;captopril 12.5 mg orally bid or tid;indapamide 2.5 mg orally qd.Treatment group was given Xuefu Zhuyu decoction 100 mL · d-1,bid on the basis of control group.All patients were treated for 90 d.The clinical symptoms and blood pressure were compared before and after treatment.Results The clinical efficacy was 95.00％ (57/60 cases) and 78.33％ (47/60 cases,P ＜0.05).After treatment,the systolic blood pressure (SBP) were (130.09 ±9.95),(113.08 ±15.24) mmHg in control group and treatment group,and diastolic blood pressure (DBP) were (84.40 ±9.05),(81.02 ±6.56) mmHg (P ＜0.05).There was 1 case of dizziness in control group,and no adverse drag reaction occurred in treatment group,with no significant difference (P ＞ 0.05).Conclusion Xuefu Zhuyu decoction combined with western medicine maybe an effective treatment on elderly patients with refractory hypertension.

OBJECTIVETo establish Biological Limit Value (BLV) for N, N-dimethylacetamide (DMAC).

METHOD201 workers in 3 spandex factories exposed to DMAC were recruited. Air samples were collected using personal air samplers, and urine samples from each works were collected at the end of shift at end of workweek. The urinary metabolite NMAC and air samples of DMAC were determined by gas chromatography (GC). Percentile and relative internal exposure (RIE) were analyzed and proposed a BLV for DMAC.

RESULTSThe number of workers who exposure to DMAC below OELs were 133 (66.2%) among 201 workers monitored. Geometric mean (range) concentration of DMAC in air was 19.4 (0.40 ∼ 300.12) mg/m(3), and that of NMAC in urine was 23.7 (1.30 ∼ 189.42) mg/g Cr. A linear correlation was found between the personal air DMAC and creatinine-adjusted NMAC levels in urine collected at the end of shift at end of workweek (F = 188.872, R(2) = 0.487,P < 0.001). The relationship can be described by the equation Log (NMAC mg/g Cr) = 0.685 + 0.455 log (DMAC mg/m(3)). According to the equation the current China OELs value of 20 mg/m(3) would lead to a mean NMAC concentration of 18.92 mg/g Cr. The 90th percentile biomonitoring result below 20 mg/m(3) 8-hour TWA is 23.9 mg MMAC mg/g Cr, and that of NMAC in urine calculated by relative internal exposure (RIE) was 19.0 mg/g Cr.

CONCLUSIONA BLV of 20 mg/g Cr NMAC in urine at the end of shift at end of workweek for DMAC was recommend by reference to official values from other countries.

Acetamides ; analysis ; urine ; Adult ; Air Pollutants, Occupational ; analysis ; Chromatography, Gas ; Female ; Humans ; Male ; Occupational Exposure ; analysis ; Threshold Limit Values

Objective To determine whether the novel surface-anchored protein SasX promotes aggregation of S.aureus and adherence of S.aureus to human nasal epithelial cells.Methods MRSA ST-239 HS770 sasX gene mutant ( HS770 △sasX) and complement [ HS770 △sasX (pRBsasX) ] were gotten by gene knock-out and complement methods.The aggregation ability of S.aureus was observed through microscope.By adherence assay which was used for detection of the adherence ability of wild type and mutant to human nasal epithelial cells and blocking experiments which detected the ability of the purified recombinant SasX protein in blocking the adherence of S.aureus to human nasal epithelial cells,we investigated the influence SasX on colonization of S.aureus.Results Compared to wild type,HS770△sasX showed a reduction in cell aggregation,while the complement had no difference with wild type in aggregation. HS770 △sasX showed a significant reduction of adherence to human nasal epithelial cells compared to wild type ( P＜0.01 ),and the complement showed a very clear increasement of adherence to human nasal epithelial cells compared to wild type(P＜0.01 ).Preincubation of nasal epithelial cells with the purified recombinant SasX protein inhibited S.aureus binding significantly.Conclusion SasX had an influence in aggregation of S.aureus and its adherence to human nasal epithelial cells.By acquiring sasX,S.aureus colonized more easily to the susceptible sites of the host,and thus caused infection.

OBJECTIVETo observe the effect of Huxin Formula on expressions of the chief reverse cholesterol transport (RCT) associated genes, caveolin-1 and scavenger receptor-BI (SR-BI) in ApoE-gene knockout [ApoE (-/-)] mice.

METHODSThirty ApoE (-/-) mice of 4-6 weeks old were randomly divided into three groups (A-C). After being fed with high-fat diet for 16 weeks, they were treated with HXF (1 mL/100 g), pravachol (0.3 mg/100 g), and saline in equal volume respectively for 16 weeks successively; in addition, a blank group was set up with 10 C57BL/6J mice of 6-week old received 16-week high-fat feeding and saline treatment. Animals were sacrificed at the termination of the experiment, their paraffin sections of aortic tissue were used to measure the size of plaque, expressions of cavolin-1 and SR-BI were detected by immunological histochemical method.

RESULTSAs compared with the blank group, levels of caveolin-1 and SR-BI were increased in Groups A and B (P<0.01); but the increase in Group A was more significant than that in Group B (P<0.05). The plaque/aorta area ratio decreased significantly in Groups A and B, but showed insignificant difference between the two groups.

CONCLUSIONHXF could obviously increase the expressions of RCT associated genes, caveolin-1 and SR-BI, promote the RCT process, so as to reduce the formation of aorta atherosclerotic plaque in ApoE (-/-) mice.

Animals ; Aorta ; drug effects ; pathology ; Apolipoproteins E ; deficiency ; genetics ; Atherosclerosis ; pathology ; Biological Transport ; drug effects ; Caveolin 1 ; metabolism ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plaque, Atherosclerotic ; pathology ; Receptors, Scavenger ; metabolism

Objective To investigate the clonal types of Staphylococcus aureus collected from 2004to 2010 in patients with blood stream infection from a Grade A tertiary care hospital in Shanghai as well as the dynamic changes and to detect the variation in antimicrobial resistance and virulence-gene content in different strain types.Methods A total of 103 nonduplicate S.aureus isolates were collected from 2004 to 2010 from inpatients with S.aureus blood stream infection from Shanghai Huashan hospital.Determination of oxacillin MICs and the type of SCCmec gene were used to screen MRSA.Typing of S.aureus isolates was identified by using multilocus sequence typing(MLST) and S.aureus-specific staphylococcal protein A typing(spa typing),PCR was used to detect the antimicrobial resistance and virulence-gene.Results Sixtysix isolates(64.1%) MRSA were detected in 103 nonduplicate S.aureus isolates,and 35 isolates were MRSA with SCCmec type Ⅱ ,Twenty-nine isolates were MRSA with SCCmec type Ⅱ,two isolates were MRSA with SCCmec type Ⅳ,Thirty-seven isolates(35.9%) were MSSA.Thirty-three MRSA isolates were ST5,Twenty-nine MRSA isolates were ST239,two MRSA isolates were ST59,one MRSA isolates was ST641 and one MRSA isolates was ST6.All of the other clones belonged to MSSA.The percentage of ST5 and ST239 were decreased significantly after 2009(ST5 was decreased from 52.9% to 15.4%; ST239 was decreased from 61.1% to 15.4%),and new clonal types MSSA increased significantly(in 2009,the percentage of ST7 was 41.7%; new clonal types such as ST188 and ST15 were detected in 2010).In 2010,it was shown that 84.6% of MSSA were isolated from S.aureus blood stream infection,nineteen isolates(18.4%) harbored mupA gene and 41 isolates(39.8%) harbored qacA/B gene in 103 nonduplicate S.aureus isolates.It was shown that 70.6% ST239 harbored qacA/B gene.Four isolates of ST398 and 1 isolates of ST9were detected which were originally from animal.There was no significant difference of the virulence gene presence in the same strain types except sasX、lukSF and arcA genes,but there were a lot of genes which were restricted to different genomic background.Conclusions The percentage of ST5 and ST239 were decreased and new clonal types of MSSA were increased significantly in S.aureus blood stream infection,antimicrobial resistance and virulence-gene were restricted to different clonal types.

ObjectiveTo investigate the distribution and effect on antibiotic resistance of the novel cell wall anchored protein-encoding gene sasX.MethodsA total of 300 S.aureus isolates were randomly collected from inpatients with S.aureusinfection in ShanghaiHuashanhospitalin 2004, 2007and 2010.Meanwhile,170 S.aureus isolates from the nasal swabs of healthy people were collected as part of a population-based community prevalence study.Typing of S.aureus isolates were identified by using multilocus sequence typing (MLST) and S.aureus-specific staphylococcal protein A typing (spa typing).Determination of oxacillin MICs was used to screen MRSA.PCR and sequencing were used to analyze sasX gene.The effect on antibiotic resistance of sasX gene was detect by disc agar diffusion drug sensitive test.ResultsThe major clonal types of the 300 S.aureus isolates collected from inpatients with S.aureus infection were ST239 ( 110,36.7％) and ST5 (122,40.7％).From 2004 to 2010,the percentage of isolates from inpatients with S.aureus infection was increased from 17％ to 39％,but sasX was only found in 0.59％ of the S.aureus isolates from the nasal swabs of healthy people.The percentage of sasX positive was increased from 47.2％ to 83.8％ in ST239.The percentage of sasX positive MRSA was increased from 26.4％ to 50.8％,but the percentage of sasX positive MSSA was about 10％.Antibiotic resistance of sasX positive strains were higher than that of sasX negative strains.Conclusions SasX gene is mainly detected in nosocomial pathogenic S.aureus and it is a possible virulence factor of S.aureus in hosptal setting.The presence of sasX gene is related to antibiotic resistance.For better understanding the real function of this novel gene,further studies such as expression of the encoded protein should be carried out.