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

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 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.

BACKGROUNDIt is a surgical dilemma when patients present with both severe heart disease and neoplasms. The best surgical treatment remains controversial. This study aimed to analyze the early and long-term results of simultaneous surgical treatment of severe heart disease and neoplasms.

METHODSWe reviewed the clinical records of 15 patients who underwent simultaneous neoplastic resection and cardiac surgery between September 2006 and January 2011. There were 5 male and 10 female patients. The mean age was (59.2 ± 12.5) years and the mean left ventricular ejection fraction was (57.4 ± 11.0)%. All patients were followed up completely for a period of 12 to 51 months (mean, (33.1 ± 11.2) months).

RESULTSFifteen patients underwent simultaneous cardiac surgery and neoplastic resection. Cardiac procedures consisted of off pump coronary artery bypass grafting (n = 7), aortic valve replacement (n = 3), mitral valve replacement (n = 3), mitral valve replacement with coronary artery bypass grafting (n = 1) and left atrial myxoma resection (n = 1). Neoplastic resection consisted of lung cancer resection (n = 5), colonic cancer resection (n = 3), gallbladder resection (n = 1), colonic cancer resection with gallbladder resection (n = 1), hysterectomy (n = 2), hysterectomy with bilateral salpingo-oophorectomy (n = 2) and left ovariectomy (n = 1). Pathological examination confirmed malignant disease in 10 patients and benign disease in 5 patients. There were no perioperative myocardial infarctions, stroke, pericardial tamponade, renal failure or hospital deaths. The most frequent complications were atrial fibrillation (33.3%), pneumonia (26.7%), low cardiac output syndrome (6.7%) and delayed healing of surgical wounds (6.7%). There was 1 late death 42 months after surgery for recurrent malignant disease. At 1 and 3 years, survival rates were 100% (Kaplan-Meier method).

CONCLUSIONSSimultaneous cardiac surgery and neoplastic resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not appear to adversely affect survival in patients with malignant disease. The long-term survival was determined by tumor stage.

Adult ; Aged ; Colonic Neoplasms ; surgery ; Female ; Heart Diseases ; surgery ; Humans ; Hysterectomy ; adverse effects ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Ovariectomy ; adverse effects ; Thoracic Surgery ; statistics & numerical data ; Treatment Outcome

OBJECTIVETo design ABC damage variable and positioning system for acetabular fracture and explore the feasibility and clinical practical value of the system through the multi-center analysis of 1122 acetabular fractures.

METHODSAccording to acetabular three-column conception, and pelvic ring lesions damage direction caused by acetabular fracture domino effect and injury degree of proximal femur joint, it defined class A as any column acetabular fracture; class B as any two-column acetabular fracture; class C as front, dome and posterior mixture acetabular fracture. Lower case English letters a, m, p represented front, dome, posterior fracture, respectively. Acetabular damage variables: 1 was simple displaced fractures; 2 was comminuted fractures; 3 was compression fractures. Pelvic ring lesions damage variables: alpha was sacroiliac joints or sacroiliac fracture horizontal separation deflection; beta was sacroiliac joints or sacroiliac fracture vertical separation deflection; gamma was pubic symphysis separation/superior and inferior ramus of pubis fracture deflection; alpha beta gamma delta was compound floating damage. Proximal humerus joint damage variables: I was femoral head fracture; II was femoral neck fracture; II was intertrochanteric fractures of femur; IV was I to III compound fracture. The ABC damage variable positioning system for acetabular fracture was made up by the above-mentioned variables. The statistics from March 1997 to February 2010 showed 1122 cases acetabular fractures with 18 cases of double side acetabular fracture and 1140 cases of acetabular fractures. The pelvics anterior-posterior view, ilium and obturator oblique view, and 2/3D-CT materials were analyzed and researched.

RESULTSEach damage variables distribution situation in 1140 cases of acetabular fracture involved A in 237 cases (20.8%), B in 605 cases (53.1%), C in 298 cases (26.1%);front column fracture in 808 cases(70.9%), dome fracture in 507 cases (44.5%), posterior fracture in 1026 cases (90%). Acetabular variables: variabe 1 in 203 cases of simple displaced fracture (17.8%); variabe 2 in 516 cases of comminuted fracture(45.3%); variabe 3 in 421 cases of compression fracture (36.9%); 249 cases of pelvic ring lesions damage (21.8%), 75 cases femoral head fracture (6.6%); 18 cases of double side acetabular fracture and relative pelvic ring and proximal humerus joint variables (1.58%). Key part and curative effect elements of 1140 cases acetabular fracture: 507 cases of dome or posterior acetabular fracture (44.5%); 421 cases of compression fracture (36.9%); 249 cases of pelvic ring variables (21.8%); 75 cases of proximal humerus joint variables (6.6%); 486 cases of simple Aa/pl/2,Bapl/2 acetabular fracture (42.6% ).

CONCLUSIONCompression fracture, especially defected compression fracture, takes important part in acetabular damage variables, and also presents that acetabular fracture with pelvic ring and proximal femoral damage variables are not rare at all. The relationship of the acetabular fracture damage variables, and its percentage shows the key points and elements in clinical treatment: weight-bearing to dome accounts for 44.5%; compression to defects account for 36.9%, pelvic ring to float accounts for 21.8%; dome fracture to double side fracture account for 6.6%. The system has significant guiding effects on clinic in terms of evaluation of injury severity, anatomic localization, difficulty index, alternative strategy, operative approach, effect of treatment,and prognosis. And the most important thing is that the system creates the comparison of damage variables in same type of fracture and the communication of homo-language and explores a new method.

Acetabulum ; injuries ; Adolescent ; Adult ; Aged ; Child ; Female ; Fractures, Bone ; classification ; diagnostic imaging ; Humans ; Male ; Medical Informatics ; methods ; Middle Aged ; Tomography, X-Ray Computed ; Young Adult