Objective: To analyze the global research competition and collaboration landscape in the field of organoids. Methods: In January 2024, papers related to organoids were retrieved from database of Web of Science. Through co-citation analysis, bibliometric analysis, and social network analysis, research hotspots, leading countries, institutions, and researchers were identified. Results: Since 1990, a total of 10 477 scientific papers have been published globally in the field of organoids, with 82.4% published since 2018. Researches have primarily focused on the construction of organoids related to tumors, liver and kidney, intestinal epithelium, human brain, and retina. The United States leads both the publications (4 632 papers) and collaboration partners (75), as well as instances (3 405). China ranks second in terms of publications (1 970 papers); however, its number of collaboration partners (54) and instances (1 194) are far lower than those reported by the United States. At the institutional level, Harvard University leads in terms of publications (534 papers), collaboration partners (347), and instances (1 495). Other high-ranking institutions outside the U.S. include the Chinese Academy of Sciences, Utrecht University in the Netherlands, Cambridge University in the UK, and the German Cancer Research Center. Professor Hans Clevers from the Netherlands is noted for having published the highest number of papers, while in China, significant contributions have been made by research teams led by Jianhua Qin and Guoqiang Hua. Conclusion: The field of organoids has experienced rapid development over the past decade, with numerous studies focused on the construction of organoids for various applications, including tumors, liver, intestine, brain, and retina. The U.S. holds a dominant position, while China is an important participant in international collaboration. Harvard University stands out as a global collaboration hub, while institutions from China, the Netherlands, the UK, and Germany serve as regional hubs.

Objective： To explore the main paths on technological development in the organoid field based on patent citation networks. Methods： This study constructs a patent citation network for the organoid field and applies the search path link count (SPLC) algorithm to calculate traversal weights for main path analysis, aiming to  investigate the technological development trajectory in this area. Results： The organoid field includes 2,250 patent applications and 12,722 patent citations. The number of patent applications has been increasing annually, with the technological developments focused on disease models, drug screening, cell culture and organoid chip. Main path analysis reveals that the most patents, twelve in total, appear on the global main path, which contains one technological route consistent with the global key-route path. While the local forward main path contains ten patents, with one technological route, reflecting China's technological trajectory in organoid development, focusing on disease mechanism research based on tumor organoids, as well as development and optimization of lung cancer organoid models. The local backward main path contains nine patents and two technological routes, reflecting the American trajectory in organoid technology, focusing on gastrointestinal organoid cultivation and disease models, stem cell-driven organ function repair, as well as cell transplantation and organ regeneration. Conclusion： This study identifies technological development trajectories through main path analysis of patents in the organoid field, providing intelligence support for R&D in organoids from a perspective of information science.

Human respiratory syncytial virus (RSV) is a common pathogen that causes lower respiratory tract infections. At present, symptomatic and supportive treatment remains the main treatment for RSV infections, while vaccination is one of the effective means to prevent such infections. Infants, the elderly and other immunocompromised people are at high risk of RSV infection. Therefore, it is important to pay attention to the safety evaluation of RSV vaccine in clinical research. This paper will discuss the safety evaluation of RSV vaccines alongside the clinical safety researches of RSV vaccines approved abroad.

Accurate prediction of pharmacokinetic parameters is crucial for the successful development of novel drugs. Traditional pharmacokinetic studies mainly utilized animals models; however, due to species differences in structure and physiology between animals and humans, the prediction of human pharmacokinetic parameters from animal experiments falls short of expectations. In recent years, the development of organ-on-a-chip (OOC) has shown considerable potential as an in vitro method for predicting pharmacokinetic and pharmacodynamic parameters in humans by constructing in vitro microphysiological systems utilizing human-derived cells. It has the potential to recapitulate key physiological parameters in the human body. This paper systematically introduces the current research status of single-chip models and multichip models in the field of pharmacokinetics, and also discusses the reliability of the translation of OOC models to in vivo circumstance, providing an overview of the both the challenges of organ-on-a-chip and the prospects for their application.

Cholestasis is a pathology common to many acute and chronic liver diseases and is mainly characterized by excessive accumulation of bile components such as bile acids (BAs) in the liver and body circulation. Clinical manifestations are jaundice, fatigue and itching, etc. The condition is protracted and difficult to cure. If not intervened in time, persistent cholestasis can further develop into liver fibrosis, cirrhosis, liver failure and even end-stage liver disease. The pathogenesis of cholestasis is complex, and there is a lack of effective therapeutic drugs. Recent studies have shown that farnesol X receptor (FXR) plays an important role in the development of cholestasis by regulating the synthesis, transport, metabolism, and reabsorption of BAs, the major components of bile, and has gradually become a hot target in the research and development of anti-cholestasis drugs. Traditional Chinese medicine (TCM) is safe, effective and has few side effects, and with the gradual deepening of research, the efficacy of TCM active ingredients or combinations in regulating FXR against cholestasis is remarkable. Through literature search and summarization, the authors systematically explored the research progress of FXR receptor-based anti-cholestasis of TCM active ingredients and combinations, with a view to providing ideas and references for the treatment of cholestasis and related drug development.

As a type of cationic polymer, chitosan is an ideal carrier for nucleic acid delivery due to its excellent biocompatibility, remarkable biodegradability and high cation density. The structure of chitosan contains a large number of amino groups, and the transfection efficiency of nucleic acid is affected by several factors like deacetylation degree, molecular weight, pH, serum and N/P ratio. Due to its superior delivery abilities, chitosan has been widely used in the delivery of DNA and RNA. In addition, chitosan is also used to deliver CRISPR/Cas9 for gene editing, which is a novel approach to disease treatment. Nevertheless, chitosan and its derivatives as gene carriers still face obstacles at both intracellular and extracellular levels that necessitate further resolution.

The tight junction protein subtype Claudin18.2 (CLDN18.2) is exclusively expressed in normal gastric mucosal epithelial cells, where it plays a crucial role in regulating transmembrane transport of substances. However, CLDN18.2 is retained in the malignant transformation of normal tissues, and is widely expressed in gastric cancer, pancreatic cancer, breast cancer and other malignant tumors. Antibody-drug conjugates (ADC) targeting CLDN18.2 simultaneous exhibit high targeting selectivity of monoclonal antibodies and high anti-tumor activity of cytotoxic drugs, making them a promising new type of biologically targeted anticancer drug with great therapeutic potential. This article reviews the clinical trial progress of CLDN18.2 ADC, providing some references for the development of related drugs.

Objective: To develop a clinical efficacy evaluation index of sputum syndrome that integrates indexes of qualitative and quantitative, subjective and objective, as well as patients and doctors, and to establish a comprehensive clinical efficacy evaluation scale for sputum pattern. Methods: Combined with the scientific formulation process of scales in China and abroad, the research design of exploratory sequences in mixed research methods was adopted. Quantitative research methods such as literature research, multi-round screening of items, and expert electronic questionnaire surveys, alongside qualitative research methods such as qualitative interviews with experts and expert consensus meetings were used to screen, interpret and optimize the items. Results: The sputum syndrome efficacy evaluation scale contained a total of 11 symptom items, including 6 local symptoms: phlegm, sputum stickiness, sputum sound, phlegm, sticky stool, and local mass; 4 systemic symptoms: obesity, heaviness, dizziness, and dizziness, as well as 1 tongue image. Conclusion: This study has established a quantitative and effective tool for evaluating the efficacy of sputum syndrome, providing a useful reference for the development and application of the evaluation criteria for the efficacy of sputum syndrome.

Objective: To evaluate the clinical adaptability of the Sputum Pattern Efficacy Evaluation Scale developed in the early stage. Methods: Reliability analysis, linear regression analysis, factor analysis and other analysis methods were used to statistically analyze the data. The feasibility, reliability, validity and responsiveness of the scale were also evaluated. Results: In terms of scale feasibility, both the acceptance rate and completion rate were 100%, with a median time to complete the scale of approximately 3 minutes. The test-retest reliability, internal total reliability and reliability of each dimension of the scale were found to be acceptable, indicating that the scale is stable and that the dimension items are reasonably set. The content validity, structural validity and criterion validity of the scale were also acceptable, indicating that the content and structure of the scale are reasonable. All items could be effectively extracted; the variance of the four common factors reflected changes in the symptoms of tangible phlegm, invisible phlegm blocking the body's qi operation, invisible phlegm flow and agglomeration, and invisible phlegm overflowing all around the body, respectively. Regarding responsiveness of the scale, through the comparison of the items, dimensions and total scores of the scale between patients with sputum pattern and non-sputum pattern in different age groups, it was found that the scale could assist distinguish the symptom performance and degree of patients with sputum pattern and without sputum pattern at different ages from different levels. Conclusion: The scale demonstrates good feasibility, reliability, validity and responsiveness, which can effectively reflect the changes in the efficacy of sputum syndrome, and can be further popularized and applied in clinical practice.

The development of anti-cancer drugs has become a prominent focus in the field of new drug research and development in China. The number of clinical trial projects for anti-cancer drugs undertaken by various medical institutions is also increasing. From the perspective of an oncology hospital, this paper analyzes and discusses the risk factors in each stage of working, summarizes the particularity of clinical trial drug management of anti-cancer drugs, based on our experience and drug management process, namely receipt, storage, dispensation and return of investigational products. The authors also put forward suggestions on clinical trial drug management to improve the quality and efficiency of drug management, which might provide references for the construction of clinical trial pharmacy and standardized drug management for clinical trials.

Objective： To investigate the effective chemical components and potential mechanisms of Xianling Gubao Capsules (XLGBC) in the treatment of Osteoporosis (OP), we employed UHPLC Q-Exactive Orbitrap-MS in combination with network pharmacology. Methods: The Hypersil Gold column was used for gradient elution utilizing a mobile phase consisting of 0.1% formic acid in water (A) and a formic acid acetonitrile solution (B). Mass spectrometry was conducted in both positive and negative ion modes. A chemical composition database for XLGBC was established, combining Xcalibur software to compare excimer ion and characteristic fragment ions, thereby chemical components were identified. Candidate active ingredients were screened using TCMSP and SwissADME. The Genegards, DisGeNET, SwissTargetPrediction and Metascape databases were used to predict and enrichg the targets of active ingredients for the treatment of OP. By combining String platform and Cytoscape software, key targets and important active components of XLGBC for anti-OP were obtained. And the molecular docking was used for preliminary verification purposes. Results: A total of 120 chemical components were identified, among which 5 compounds were identified in XLGBC for first time. Additinally, 63 candidate active ingredients and 447 targets for the treatment of OP were screened. Enrichment analysis showed that regulation of hormone levels, osteoclast differentiation, PI3K-AKT signaling pathway, etc., are involved. The EGFR and PIK3R1 targets are closely related to multiple pathways, and were considered as the key target protein. The 6 main core components of XLGBC therapy for OP were obtained via network topology analysis of protein-protein interaction (PPI). And molecular docking indicated that the components have strong binding capacity to the key target proteins. Conclusion: The comprehensive elucidation of various chemical compositions in XLGBC reveals the main chemical components and potential mechanisms of XLGBC on OP, which provides a scientific reference for its effective substances research.

Objective： In this study, a nanostructured lipid carrier (NLC) was loaded with methotrexate (MTX) and cucurbitacin B (CuB), resulting in the formulation MTX-CuB-NLC, which was optimized and evaluated in vitro. Methods： An in vitro high-performance liquid chromatography analysis method of MTX and CuB was established. The MTX-CuB-NLCs were prepared using a melt emulsification low-temperature curing method. A single-factor analysis was conducted by using encapsulation efficiency and drug loading as evaluation indicators, to identify the optimal prescription using Box-Behnken design response surface methodology. The particle size, polydispersity index (PDI), and Zeta potential of the formulation were evaluated by means of nanoparticle size analyzer. The appearance and morphology of the formulation were examined through transmission electron microscopy. And its storage stability was investigated by changes in particle size and Zeta potential. The in vitro drug release of the drug delivery system was assessed using the dialysis bag method. Results： The optimal formulation of MTX-CuB-NLC was as follows: MTX 0.7 mg, CuB 0.5 mg, mixed fatty acid glyceride 104 mg, ELP 96 mg, water phase volume 4 mL,  and PVA 44 mg. The entrapment efficiencies were MTX (61.03±2.40)%, CuB (81.02±1.61)%. The drug loading capacities were MTX (0.25±0.02)%, CuB (0.23±0.02)%. The average particle size (44.13±1.40) nm, PDI (0.279±0.12), Zeta potential -(17.10±4.98) mV. Under transmission electron microscopy, the particles appeared quasi-circular with smooth surface and excellent dispersion. They showed favorable stability during storage over 14 days. The cumulative release of MTX and CuB in 48 h was (86.01±2.25)% and (73.72±1.97)%, respectively. Conclusion： In this study, MTX-CuB-NLC was successfully prepared. The preparation method was stable and sustained-release, which laid the foundation for the further study of the preparation.

Objective: To synthesize the β-carboline-cinnamic acid skeleton compound B4, a new method for its determination was established and the stability and hemolytic characteristic of B4 were evaluated. Methods: β-Carboline was synthesized by the Pictet-Spengler reaction using tryptamine as the raw material. Subsequently, the β-carboline-cinnamic acid compound B4 was synthesized by the condensation reaction of β-carboline and 4-chlorocinnamic acid. Compound B4 was qualitatively and quantitatively analyzed by HPLC, with optimization of chromatographic conditions performed alongside methodological verification. The stability of compound B4 in simulated gastric and intestinal fluid was assessed using this detection method. The hemolytic evaluation of compound B4 was conducted in accordance with the relevant provisions of the hemolytic and coagulation test method. Results: The structural determination of compound B4 was conducted using ¹H-NMR, ¹³C-NMR, and ESI-MS. The optimal chromatographic conditions were established as: YMC-Pack ODS-A column (250 mm×4.6 mm，5 μm), with a mobile phase of methanol and water at V(methanol)∶V(water) of 90∶10, employing iso-degree elution at a  flow rate of 1.0 mL·min^－1 and detection wavelength of 278 nm. The linear range of the method was 1~100 μg·mL^－1. The linear equation was y=126.96x+199.85 (R²=0.999 4). And the average recovery rate was 104%. The methanol solution of the compound remained stable for at least 24 h at 25 ℃. Compound B4 was unstable in acidic artificial gastric fluid where it rapidly degraded, while it was relatively stable and slowly degraded in artificial intestinal fluid until it was completely degraded after 150 min. At the same time, the hemolytic test of the compound B4 showed no visible hemolysis and coagulation phenomenon, thereby complying with the relevant provisions of pharmacopoeia. Conclusion: A method for content determination of compound B4 was established, which is a newly synthesized innovative small molecule. B4 exhibits greater stability in alkaline solution than in acidic solution.

Objective: To explore methodologies for the economic evaluation of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Methods: A literature search was conducted from inception until January 15, 2024, across PubMed, Embase, Scopus, Cochrane Library, and Web of Science databases to identify studies focusing on the economic aspects of PCSK9 inhibitors. The included studies were evaluated using the 2022 version of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results: Among 30 economic evaluation studies of PCSK9 inhibitors for the treatment of cardiovascular disease, 27 utilized modeling for economic assessment, predominantly employing Markov models. These studies varied in terms of duration and health state quantities. In 23 studies, LDL-C reduction was extrapolated for efficacy assessment, while adverse drug reactions were not considered. Conclusion: The current literature mainly evaluates the economic value of drugs using Markov models, but there are limitations in the selection of drug efficacy indicators, and whether adverse drug reactions are included in the analysis.