OBJECTIVE To provide reference for the establishment and improvement of the regulatory system of patients’ medicine instructions in China. METHODS Through searching the official website of the European Medicines Agency （EMA） and related literature， the definition， basic nature， and content of patients’ medicine instructions in the European Union were introduced， and the characteristics of the management system of patients’ medicine instructions in the European Union were analyzed in terms of the management department， approval and change procedures， readability requirements and information accessibility requirements. At the same time， the pilot situation of patients’ medicine instructions in China， as well as problems in the paths of classification and management， readability of content， and information timeliness were analyzed to put forward suggestions. RESULTS & CONCLUSIONS European Union had a dedicated department for the management of medicine instructions； the approval and change procedures for patients’ medicine instructions were clear， the readability requirements were detailed， the readability verification program with patient participation was established， and multi-channel and timely information disclosure was adopted. It is recommended that China establish a mechanism to categorize and manage professionals’ and patients’ medicine instructions， guide multiple parties to participate in the design of patients’ medicine instructions and refine the readability requirements， and improve the mechanism for disclosure of medicine instructions to enhance the timeliness of medication information.

Objective To assess the effect of early nutritional intervention on the patients with respiratory diseases at nutritional risk. Methods A total of 130 patients with respiratory disease who were hospitalized in Shanghai Fifth People’s Hospital, Fudan University between May 2023 and December 2024 and had a nutritional risk screening 2002 score ≥3 points. Based on the initiation time of nutritional intervention, patients were divided into an early group (≤5 days, n＝65) and a late group (＞5 days, n＝65). Results In the early group, prealbumin (P-ALB) and retinol-binding protein (RBP) levels were significantly higher (P＜0.01), C-reactive protein (CRP), procalcitonin (PCT) levels were significantly lower after intervention (P＜0.05). Compared with the late group, the hospital costs were lower and hospital stays were shorter in the early group (P＜0.001). Spearman analysis showed ALB, P-ALB, and total protein (TP) were negatively correlated with hospital costs (r＝－0.37, －0.20, and－0.22, P＜0.05). RBP, ALB, P-ALB, and lymphocyte count (LYM) were negatively correlated with CRP (r＝－0.30, －0.26, －0.37, －0.18, P＜0.01), RBP, ALB, P-ALB, hemoglobin (HB), and TP were negatively correlated with PCT (r＝－0.23,－0.36, －0.40, －0.30, －0.19, P＜0.05). Conclusions For patients with respiratory diseases, early nutritional assessment should be underwent, and for patients with nutritional risk screening 2002 score ≥3 points, early nutritional intervention could improve the nutritional status and alleviate inflammatory response, promote recovery, shorten the hospital stays.

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

OBJECTIVE To provide references and recommendations for improving the regulatory framework for cell and gene therapy products and treatments in China. METHODS This study systematically examined the “dual-track regulatory” frameworks for regenerative medicine products and treatments in Japan and the Republic of Korea， summarized their beneficial experiences， and explored optimization strategies for China’s regulatory practices. RESULTS & CONCLUSIONS Both Japan and the Republic of Korea have established clear management processes for two distinct pathways “registered clinical trials for regenerative medicine products” and “clinical research on regenerative medicine treatments” guided by shared principles of “risk stratification” and “full lifecycle oversight”. Based on these findings， it is recommended that China： strengthen top-tier legislative framework to explicitly delineate the regulatory scope governing cell and gene therapy products and treatments； clarify the jurisdictional responsibilities of relevant regulatory bodies to enhance oversight efficacy； appropriately calibrate the regulatory scope， and adopt a balanced regulatory approach that harmonizes standardization with innovation incentives， thereby accelerating the clinical translation of regenerative medicine products.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.