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.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

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*

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective To study the expression levels of serum complement C1q/tumor necrosis factor-related protein 6(CTRP6)in women in early pregnancy and to explore its relationship with gestational diabetes mellitus(GDM).Methods Women at the Second Affiliated Hospital of Zhengzhou University from March 2021 to March 2022 were prospectively and consecutively selected from 10 to 13 weeks gestation for outpatient obstetric check-ups.The age,height,weight,and time of last menstruation of pregnant women were collected,and the levels of total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL),low density lipoprotein(LDL),fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS)and CTRP6 were measured in early pregnancy,and the pre-pregnancy body mass index(BMI),baseline BMI,prenatal BMI,and homeostatic model assessment of insulin resistance(HOMA-IR)were calculated.All pregnant women underwent a 75g oral glucose tolerance test at 24-28 weeks of gestation and were divided into GDM group and normal glucose tolerance(NGT)group according to the test results.The clinical data and laboratory indexes of the two groups in early pregnancy were compared,and the correlation between serum CTRP6 and various indexes in early pregnancy and its relationship with GDM were analyzed.Results A total of 213 maternal cases were enrolled,and 203 cases were completed for follow-up.Among them,52 mothers were diagnosed with GDM,with a GDM prevalence rate of 25.62%.Serum CTRP6,age,pre-pregnancy BMI,baseline BMI,antenatal BMI,TC,LDL,FPG,HbA1c,FINS,and HOMA-IR were higher in GDM group compared to NGT group,with a statistically significant difference(P<0.05).CTRP6 in early pregnancy was positively correlated with age,pre-pregnancy BMI,baseline BMI,prenatal BMI,TG,LDL,FPG,HbA1c,FINS,HOMA-IR,and negatively correlated with HDL(P<0.05).After correcting for age,BMI,glycolipid metabolism index and HOMA-IR,CTRP6 in early pregnancy remained an independent factor in the development of GDM.Conclusion Elevated serum CTRP6 in early pregnancy is associated with GDM and is an independent risk factor for GDM.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

Objective:To compare the image quality and the diagnostic efficiency for breast malignant lesions using simultaneous multi-slice single shot echo planar imaging (SMS+SS-EPI) and readout segment of long variable echo trains (RESOLVE) for breast diffusion-weighted imaging (DWI).Methods:This study was a cross-sectional study. Clinical and imaging data of 102 patients with breast lesion from March 2021 to February 2023 in the First Hospital Affiliated to Ningbo University were prospectively analyzed. All patients underwent routine breast MRI scans and cross-sectional RESOLVE and SMS+SS EPI sequence DWI, and the image quality of 2 types sequences of DWI was evaluated. The subjective evaluation was based on a 5-point scale, including geometric distortion, artifact blurring, fat suppression, overall image quality, and lesion conspicuity of the breast. The objective evaluation included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) value of the lesion. Wilcoxon signed rank sum test was used to compare the subjective and objective parameters between the two sequences. Finally, the receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the effectiveness of ADC values for diagnosing breast malignant lesions based on two sequence images.Results:All 102 female patients had single lesions, aged from 25 to 68 years and 60 lesions were malignant and 42 were benign. The acquisition time for SMS+SS-EPI sequence imaging was 1 min 50 s, and the acquisition time for RESOLVE sequence imaging was 3 min 43 s.The subjective scores from both SMS+SS-EPI and RESOLVE sequence were over than 3 points. The geometric distortion, artifact blurring, and overall image quality scores of RESOLVE sequence images were higher than those of SMS+SS-EPI (all P<0.001). The overall lesion conspicuity score, malignant lesion conspicuity score, and benign lesion conspicuity score of DWI and ADC images combined with SMS+SS-EPI sequence were higher than those of the RESOLVE sequence (all P<0.05). There were no statistically difference in SNR, CNR, overall ADC value, malignant ADC value, and benign ADC value between SMS+SS-EPI and RESOLVE sequence DWI images of breast lesions (all P>0.05). The AUC of RESOLVE sequence ADC value in diagnosis of breast cancer was 0.973, the sensitivity was 0.929, and the specificity was 0.915; The AUC of SMS+SSC-EPI sequence ADC value in diagnosis of breast cancer was 0.956, the sensitivity was 0.977, and the specificity was 0.850. Conclusions:In breast DWI, the subjective score of SMS+SS EPI image quality can basically meet the diagnostic requirements and the conspicuity of lesions is better than that of the RESOLVE sequence. Both have good diagnostic efficacy for malignant breast lesions.

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.

Objective To explore the relationship between C1q tumor necrosis factor related protein 13(CTRP13)and gestational diabetes mellitus(GDM),and the predictive value of CTRP13 for adverse pregnancy outcomes in GDM patients.Methods A total of 163 pregnant women who underwent prenatal examination in the Second Affiliated Hospital of Zhengzhou University from January to May 2023 were enrolled in GDM group(n=83)and normal glucose tolerance(NGT)group(n=80)according to the results of oral glucose tolerance test at 24-28 weeks of gestation.Collect general information,biochemical data,and adverse pregnancy outcomes from two groups of subjects.Analyze the correlation between serum CTRP13 and glucose and lipid metabolism indicators in GDM pregnant women.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of CTRP13 for adverse pregnancy outcomes in GDM pregnant women.Results The pre pregnancy body mass index,prenatal body mass index,triglycerides,total cholesterol,low density lipoprotein,fasting blood glucose,2-hours plasma glucose,glycosylated hemoglobin,fasting insulin,and homeostasis model assessment of insulin resistanc index in GDM group was significantly higher than those in NGT group,while CTRP13 was significantly lower than that in NGT group(P＜0.05).Serum CTRP13 was negatively correlated with total cholesterol,triglycerides,low density lipoprotein,2-hours plasma glucose,and glycosylated hemoglobin in GDM patients(P＜0.05).The incidence of adverse pregnancy outcomes such as gestational hypertension and premature rupture of membranes in GDM group were significantly higher than those in NGT group(P＜0.05).The area under the curve of serum CTRP13 for predicting adverse pregnancy outcomes in GDM pregnant women was 0.805,with sensitivity and specificity of 75.80％and 76.00％,respectively.Conclusion Serum CTRP13 is associated with glucose and lipid metabolism in GDM pregnant women,and is a potential biomarker for predicting adverse pregnancy outcomes in GDM pregnant women.