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.

Objective To evaluate the bioequivalence of the vardenafil hydrochloride tablets in fasting and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A randomized,open,single-dose,two-preparation,two-sequence,two-period,crossover design was used,and 40 healthy male subjects enrolled in the fasting state and 66 healthy male subjects enrolled in the fed state.The trial was conducted in two cycles,with 20 mg of either the subject formulation or the reference formulation,vardenafil hydrochloride tablets,being administered in each cycle.The drug concentration of vardenafil in plasma was determined by the liquid chromatography-tandem mass spectrometry(LC/MS-MS)method.Pharmacokinetic parameters were calculated using the non-compartment model,and the safety evaluation indexes were statistically analyzed using SAS 9.4 or above version program data statistical software.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fasting state:Cmaxwere(34.94±18.33)and(36.69±19.45)ng·mL-1;AUC0-t were(74.38±34.11)and(74.25±33.37)ng·mL-1·h;AUC0-∞ were(76.70±34.36)and(76.46±33.84)ng·mL-1·h,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fed state:Cmax were(22.84±12.48)and(21.68±11.12)ng·mL-1;AUC0_twere(70.82±35.88)and(72.71±34.63)ng·mL-1·h;AUC0-∞ were(73.48±36.44)and(75.29±35.12)ng·mL-1·h,respectively.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters such as Cmax,AUC0-t and AUC0-∞ of the prototype drug vardenafil in plasma after oral administration of 20 mg of the test and reference formulations of vardenafil tablets to the subjects in fasting and postprandial states fell within the equivalence interval of 80.00％to 125.00％.Conclusion The subject formulation of vardenafil hydrochloride tablets was bioequivalent to the reference formulation in fasting and fed conditions in healthy Chinese subjects.

Objective To investigate the protective effect of total saponins of Panax japonicus(TSPJ)against CCl4-induced acute liver injury(ALI)in rats and explore the underlying pharmacological mechanisms.Methods Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water,100 mg/kg biphenyl bisabololol,or 50,100,and 200 mg/kg TSPJ during modeling(n=8).Liver functions(AST,ALT,TBil and ALP)of the rats were assessed and liver pathologies were observed with HE staining.Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue;ELISA was used to determine the levels of T-SOD,GSH-Px,and MDA.Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue.Results Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI.In the rat models of ALI,treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST,ALT,ALP,TBil and MDA and decrease of T-SOD and GSH-Px levels(all P<0.01).The rat models of ALI showed significantly increased expression of p-NF-κB(P<0.01),decreased expressions of PI3K,p-Akt and SIRT6 proteins,and elevated expression levels of p-NF-κB,TNF-α and IL-6 proteins in the liver,which were all significantly improved in the treatment groups(P<0.05 or 0.01).Conclusion TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver viaregulating the PI3K/Akt and SIRT6/NF-κB pathways.

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Objective To investigate the protective effect of total saponins of Panax japonicus(TSPJ)against CCl4-induced acute liver injury(ALI)in rats and explore the underlying pharmacological mechanisms.Methods Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water,100 mg/kg biphenyl bisabololol,or 50,100,and 200 mg/kg TSPJ during modeling(n=8).Liver functions(AST,ALT,TBil and ALP)of the rats were assessed and liver pathologies were observed with HE staining.Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue;ELISA was used to determine the levels of T-SOD,GSH-Px,and MDA.Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue.Results Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI.In the rat models of ALI,treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST,ALT,ALP,TBil and MDA and decrease of T-SOD and GSH-Px levels(all P<0.01).The rat models of ALI showed significantly increased expression of p-NF-κB(P<0.01),decreased expressions of PI3K,p-Akt and SIRT6 proteins,and elevated expression levels of p-NF-κB,TNF-α and IL-6 proteins in the liver,which were all significantly improved in the treatment groups(P<0.05 or 0.01).Conclusion TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver viaregulating the PI3K/Akt and SIRT6/NF-κB pathways.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objectives:To investigate the feasibility of using bedside echocardiography on the evaluation of potential donors with different causes of brain death for adult heart transplantation. Methods:Bedside echocardiographic and clinical data of consecutive potential donors for adult heart transplantation evaluated by the team of our institution from February 2018 to December 2020 were retrospectively analyzed.Based on different causes of brain death,the potential donors were divided into stroke(ischemic or hemorrhagic,n=398)and non-stroke(head trauma,brain tumor,anoxia,n=272)groups.The clinical and echocardiographic features were compared between the two groups.A total of 350 donors were assigned to our hospital by the China Organ Transplant Response System and met the inclusion criteria for donor selection.There were 195 cases in the stroke group and 155 in the non-stroke group.Retrieval operations were performed and the retrieval rate of hearts for transplantation in stroke donors was compared to that in non-stroke donors. Results:(1)Among the 670 potential heart donors,compared with the non-stroke group,donors in the stroke group were significantly older,had higher body mass index,larger left ventricular end-diastolic diameter,thicker interventricular septum,higher rates of echocardiographic abnormalities,higher prevalence of hypertension(all P<0.001).Among the 670 potential heart donors,17.5%(117 cases)did not meet the echo selection criteria,the common causes were left ventricular hypertrophy(59 cases,50.4%),left ventricular ejection fraction<50%(27 cases,23.1%),wall motion abnormalities(21 cases,17.9%),and left ventricular dilation(14 cases,12.0%).(2)Among the 350 donors who had met the selection criteria and assigned to our hospital by the China Organ Transplant Response System and underwent retrieval operation,70.3%(246 cases)were successfully procured,110 cases(44.7%)in the stroke group and 136 cases(55.3%)in the non-stroke group.The retrieval rate of stroke donors(110/195,56.4%)was lower compared with that of non-stroke(136/155,87.7%,P<0.001),104 cases(29.7%)were not retrieved,and the leading cause of unsuccessful organ retrieval was the occlusion of at least one major coronary artery(91 cases,87.5%). Conclusions:Bedside echocardiography is of great value as a screening tool for cardiac donors.Cardiac structures of the potential donor with stroke as the cause of brain death were different from those with non-stroke causes.The retrieval rate of stroke donors was lower than that of non-stroke donors,even if the initial criteria for donor selection were fulfilled.

Aim To invepredict the mechanism of ac-tion and targets of the traditional Chinese medicine compound Zheng Gan Decoction against hepatocellular carcinoma based on bioinformatics,and to experimen-tally verify the mechanism of anticancer action of Zheng Gan Decoction against DEN-induced hepatocellular carcinoma in a rat model.Methods The compounds of CZLF were collected from TCMSP and HERB Herbal Histology Database,and the potential targets of CZLF were predicted from Uniprot Protein Database,and the disease targets of hepatocellular carcinoma were searched with the help of OMIM,TTD,and Gene Cards databases,and then Venny analysis was per-formed on the targets of the disease-drugs,and then the protein-drug interactions(PI)of CZLF were mapped by String database,which was used for the study.After that,we used String database to draw pro-tein-protein interaction(PPI)network,R 4.1.3 soft-ware and Metascape database to enrich gene ontology(GO)and analyze KEGG signaling pathway for the core intersected targets,and finally,we used Cyto-scape 3.8.2 software for visualization to construct"compound-pathway-target-disease".Lastly,Cytoscape 3.8.2 software was used to visualize and construct a"compound-pathway-target-disease"network diagram,which was finally verified by Western blot experiment.Results Bioinformatics results showed that there were 171 common targets between Zheng Gan Decoction and diseases,and Zheng Gan Decoction might exert its an-ticancer effect through the main active ingredients such as lignans,quercetin,β-glutosterol,ivy saponin,etc.,as well as through the core protein targets such as CASP3,BCL2,AKT1,IL6,etc.,and the modula-tion of the Hippo signaling pathway and PI3K-Akt sig-naling pathway.The results of animal experiments showed that the expression content of apoptosis-related proteins caspase-3,BCL-2 and Bax was detected by Western blot,and the expression of Bax and caspase-3 proteins was up-regulated and the expression of Bcl-2 protein was down-regulated in the treatment group of Zheng Gan Decoction.Conclusions This study sug-gests that Zheng Gan Decoction may inhibit the growth of hepatocellular carcinoma cells and promote the apop-tosis of hepatocellular carcinoma cells by regulating the apoptosis-related proteins of caspase-3,Bcl-2,and Bax,so as to achieve the effect of anti-hepatocellular carcinoma.

A convolutional neural network-based algorithm is proposed for calculating lower limb joint angle in X-ray films.After identifying the region of interest of a specific category in X-ray films through Yolov5 object detection model,U-Net model is used to perform heat map regression for identifying the key feature points,and then the lower limb joint angle is calculated.The results show that the proposed algorithm has higher accuracy than the previous algorithms and can obtain accurate and reliable results,providing references for clinical research and practice.