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.

Esophageal cancer （EC） is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA （miRNA） is an important regulator in tumor occurrence and development， and can participate in malignant biological behaviors such as tumor cell proliferation， invasion， metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects， wide range of effects， and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine （including curcumin， Tussilago farfara polysaccharides， Atractylodes macrocephala polysaccharides and ophiopogonin B） and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p （miR-532-3p）， miR-551b-3p， miR-99a， miR-34a， miR-199a-3p and miR-377； and the active ingredients/parts of traditional Chinese medicine （including chrysin and Actinidia arguta extract）， and Chinese herbal formulas （including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction） could down-regulate the expressions of miRNAs such as miR-199a-3p， miR-451 and miR-21， which could regulate the expressions of signaling pathways （phosphoinositide 3-kinase/protein kinase B， etc.） or their downstream protein（zinc-finger and homeobox protein 1， etc.） or enzymes（thymidine kinase-1， etc.）， inhibit the proliferation， invasion and metastasis of EC cells and induce apoptosis， thereby ultimately achieving the purpose of preventing the disease from aggravating.

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise， and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa， causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue， which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B （NF-κB） signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation， autophagy， apoptosis， and inflammatory response of esophageal epithelial cells and tumor cells， accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently， there is no specific treatment for reflux esophagitis and esophageal cancer， and large side effects often appear. Therefore， finding a promising and safe drug remains a top priority. In recent years， traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway， and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， but there is a lack of comprehensive and systematic elaboration. Therefore， this paper summarized the relevant studies in recent years， analyzed the relationship among NF-κB signaling pathway， reflux esophagitis， esophageal cancer， and transformation from inflammation to cancer， and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

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.

Studies on chemical constituents in the rhizome of Dalbergia rimosa Roxb. The chemical constituents from the ethyl acetate part of D. rimosa were isolated and purified by silica gel, MCI gel, Sephadex LH-20 gel and semi-preparative HPLC, and the stuctures were identified by spectral method. Thirteen compounds were isolated from the ethyl acetate part of the rhizome of D. rimosa and identified as dalbergiaisoflavones A, B (1, 2), formononetin (3), 7,4′-dimethoxyisoflavone (4), 4′,6,7-trimethoxyisoflavone (5), biochanin A (6), prunetin (7), 7-O-methyltectorigenin (8), 3′-hydroxydaidzein (9), orobol 7,3′-dimethyl ether (10), 2′,7-dihydroxy-4′,5′- dimethoxyisoflavone (11), pruinosanone E (12), caviunin (13). Compounds 1 and 2 are new compounds, and compounds 3-13 were isolated from this plant for the first time. Compounds 9 and 11 had remarkable scavenging effect on DPPH free radicals.

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 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.

ObjectiveExisting artificial vision devices can be divided into two types: implanted devices and extracorporeal devices, both of which have some disadvantages. The former requires surgical implantation, which may lead to irreversible trauma, while the latter has some defects such as relatively simple instructions, limited application scenarios and relying too much on the judgment of artificial intelligence (AI) to provide enough security. Here we propose a system that has voice interaction and can convert surrounding environment information into tactile commands on head and neck. Compared with existing extracorporeal devices, our device can provide a larger capacity of information and has advantages such as lower cost, lower risk, suitable for a variety of life and work scenarios. MethodsWith the latest remote wireless communication and chip technologies, microelectronic devices, cameras and sensors worn by the user, as well as the huge database and computing power in the cloud, the backend staff can get a full insight into the scenario, environmental parameters and status of the user remotely (for example, across the city) in real time. In the meanwhile, by comparing the cloud database and in-memory database and with the help of AI-assisted recognition and manual analysis, they can quickly develop the most reasonable action plan and send instructions to the user. In addition, the backend staff can provide humanistic care and emotional sustenance through voice dialogs. ResultsThis study originally proposes the concept of “remote virtual companion” and demonstrates the related hardware and software as well as test results. The system can not only achieve basic guide functions, for example, helping a person with visual impairment to shop in supermarkets, find seats at cafes, walk on the streets, construct complex puzzles, and play cards, but also can meet the demand for fast-paced daily tasks such as cycling. ConclusionExperimental results show that this “remote virtual companion” is applicable for various scenarios and demands. It can help blind people with their travels, shopping and entertainment, or accompany the elderlies with their trips, wilderness explorations, and travels.