To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

To standardize the clinical application of oral Chinese patent medicines （CPMs）， and address the safety issues arising from their dosage form characteristics， irrational clinical use， and the lack of targeted pharmacovigilance systems， the China Association of Chinese Medicine organized the formulation and release of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines， aiming to inform the safe clinical use of oral CPMs and related pharmacovigilance work. According to the principles of GB/T1.1—2020 and the Drug Administration Law of the People's Republic of China （2019 revision）， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， led a drafting group comprising 18 institutions. After multiple rounds of expert interviews， literature retrieval， evidence screening， and extensive solicitation of opinions， the Guidelines were registered internationally. Systematic standardization focused on safety monitoring， risk identification， assessment， control， and other aspects. The Guidelines clarified the characteristics of oral CPMs in terms of safety monitoring， known risks， and potential risks， compared to non-oral CPMs. Then， risk control measures were proposed， including medication in special populations and irrational medication. As a special guideline for pharmacovigilance in the clinical application of oral CPMs， the Guidelines systematically construct a technical system in line with the characteristics of traditional Chinese medicine （TCM）， which is essential for improving the clinical safety management of oral CPMs and provides an important reference for medical institutions， pharmaceutical manufacturers， and regulatory authorities.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Cell models can simulate a variety of life states and disease developments, including single cells, two-dimensional (2D) cell cultures, three-dimensional (3D) multicellular spheroids, and organoids. They are essential tools for addressing complex biochemical questions. With continuous advancements in biological and cellular analysis technologies, in vitro cellular models designed to answer scientific questions have evolved rapidly. Early in vitro models primarily relied on 2D systems, which failed to accurately replicate the complex cellular compositions and microenvironmental interactions observed in vivo, let alone support sophisticated investigations into cellular biological functions. Subsequent improvements in cell culture techniques led to the development of 3D culture-based models, such as cellular spheroids. The advent of pluripotent stem cell technology further advanced the development of organoid systems, which closely mimic human organ development. Compared to traditional 2D models, both 3D cellular models and organoids offer significant advantages, including personalization and enhanced physiological relevance, making them particularly suitable for exploring molecular mechanisms of disease progression, discovering novel cellular and biomolecular functions, and conducting related studies. The imaging analysis of common cellular models primarily employs labeling-based methods for in situ imaging of targeted genes, proteins, and small-molecule metabolites, enabling further research on cell types, states, metabolism, and drug efficacy. However, these approaches have drawbacks such as poor labeling specificity and complex experimental procedures. By using cells as experimental models, mass spectrometry technology combined with morphological analysis can reveal quantitative changes and spatial distributions of various biological substances at the spatiotemporal level, including metabolites, proteins, lipids, peptides, drugs, environmental pollutants, and metals. This allows for the investigation of cell-cell interactions, tumor microenvironments, and cellular bioinformational heterogeneity. The application of these cutting-edge imaging technologies generates vast amounts of cellular data, necessitating the development of rapid, efficient, and highly accurate image data algorithms for precise segmentation and identification of single cells, multi-organelle structures, rare cell subpopulations, and complex cellular morphologies. A critical focus lies in creating deep learning models and algorithms that enhance the accuracy of cellular visualization. At the same time, establishing more robust data integration tools is essential not only for analyzing and interpreting outputs but also for effectively uncovering the biological significance of spatially resolved mass spectrometry data. Developing a cell imaging platform with high versatility, operational stability, and specificity to enable data interoperability will significantly enhance its utility in clinical research, thereby advancing investigations into disease molecular mechanisms and supporting precision diagnostics and therapeutics. In contrast to genomic, transcriptomic, and proteomic information, the metabolome can rapidly respond to external stimuli and cellular physiological changes within a short timeframe. This rapid and precise reflection of ongoing cellular state alterations has positioned spatial metabolomics as a pivotal approach for exploring the molecular mechanisms underlying physiological and pathological processes in cells, tissues, and organisms. In this review, we summarize research on cell imaging based on mass spectrometry technologies, including the selection and preparation of cell models, morphological analysis of cell models, spatial omics techniques based on mass spectrometry, mass cytometry, and their applications. We also discuss the current challenges and propose future directions for development in this field.

Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To explore the relationship between bedtime procrastination and fear of missing out and the intervention effect of aerobic exercise on bedtime procrastination,so as to provide a theoretical basis and practical reference for remedying bedtime procrastination.Methods Totally 988 students were selected through random sampling and then surveyed with the bedtime procrastination scale and the fear of missing out scale.Correlation and regression analyses were performed to explore the relationship between bedtime procrastination and fear of missing out.A total of 36 students were recruited from the 988 students to participate in the exercise intervention and they were assigned into an exercise group and a control group by the random number table method,with 18 students in each group.The exercise group performed aerobic exercise for 12 weeks,while the control group maintained daily activities.The participants' scores on the bedtime procrastination scale and the fear of missing out scale were recorded before and after the intervention and compared.Results The fear of missing out was positively correlated with bedtime procrastination among college students(r=0.214,P<0.001),and it was an important predictive factor for bedtime procrastination(β=0.241,P<0.001).After the intervention,the scores of bedtime procrastination scale decreased in the exercise group(t=2.277,P=0.036),while there was no significant difference in the scores of the control group before and after intervention(t=-0.787,P=0.442).Conclusions A high level of fear of missing out indicates severe bedtime procrastination.And 12-week exercise intervention could remedy bedtime procrastination.
Humans ; Fear ; Exercise ; Male ; Female ; Procrastination ; Young Adult ; Cross-Sectional Studies ; Students/psychology* ; Adult ; Surveys and Questionnaires ; Adolescent

In the field of substance detection,ion dissociation techniques have become crucial for enhancing qualitative accuracy.By applying external energy to induce dissociation of ions in the substance being analyzed,the internal structural information can be obtained,thereby improving qualitative capabilities.Current research on ion dissociation techniques primarily focuses on tandem mass spectrometry,which typically requires a vacuum environment.However,research on ambient ion dissociation techniques is less developed,with some progress made in the field of tandem ion mobility spectrometry.Recently,the development of field-induced dissociation(FID)in this area has enabled ambient dissociation of various explosive and volatile alcohol ions.Nevertheless,the limitation imposed by the maximum breakdown field of air restricts the energy of the electric field,making it challenging to dissociate ions with high energy requirements,such as those of drugs.To address this issue,in this work,an ambient heat-induced dissociation(HID)technique based on high temperatures was proposed,in which an ambient ion heat-induced dissociation unit was developed and integrated into a home-made ion trap mass spectrometer.Experiments were conducted on four representative drug samples,e.g.methamphetamine,heroin,cocaine,and ketamine.The parent ions mass spectra,low vacuum collision-induced dissociation(CID)mass spectra and ambient HID mass spectra for each sample were obtained.By analyzing and comparing the fragmentation products from ambient and low vacuum dissociation,the feasibility of the ambient HID technique was verified.This technique provided a method for ion dissociation in single mass analyzers without tandem mass spectrometry capability and offered a new research direction for the future development of tandem ion mobility spectrometry.