Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.

Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

Objective:To investigate the killing effect of the oncolytic virus Rigvir on six different colorectal cancer cell lines in vitro and differences in the sensitivity of different cell lines to Rigvir,to analyze the differentially expressed genes and signaling pathways be-tween sensitive and insensitive cells and the reasons for such differences,to explore the killing mechanism of the oncolytic virus Rigvir on colorectal cancer cells based on experimental results,and to lay a theoretical foundation for the use of the oncolytic virus Rigvir as a novel immunotherapeutic drug for the treatment of colorectal can-cer.Methods:Cell Counting Kit-8(CCK-8)assay was used for quantitative assessment of the inhibition rate of Rigvir on cells,and the Annexin V-FITC\PI method was used to measure the apoptosis rate of sensitive cell lines and preliminarily analyze its killing mechanism.Bioinformatics techniques were used to investigate the differentially expressed genes and signaling pathways between sensitive and insensitive cells,and Western blot experiments were used for validation and detecting the expression of apoptosis factors.High expression of upstream factors in differential signaling pathways,and application of real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and WB to detect the effect of Rigvir on the expression levels of target genes and proteins in overexpressing sensitive cell lines.Results:SW480 and HT29 were sensitive to the oncolytic virus Rigvir,others had relatively insensi-tive(P<0.001).However,the inhibitory effect of Rigvir with two concentration gradients on HT29 was more significant(P<0.001).After 48 hours of infection,the cell inhibition rate of SW480 cells no longer increased with the prolongation of infection time(F=52.010,P=0.147),but it was more sensitive to changes in virus concentration(F=13.490,P<0.001).On the contrary,changes in virus concentration had no significant effect on the inhibition rate of HT29 cells(F=8.450,P=0.281),but the inhibition rate continued to in-crease after 48 hours with the prolongation of infection time(F=24.380,P<0.001).The apoptosis rate of sensitive group cells gradually increased with the prolongation of infection time(P<0.001),which mainly characterized by late stage apoptosis and necrotic cells.Through bioinformatics techniques,significant differences were observed in the classic PI3K/Akt/mTOR signaling pathway between the sensitive and insensitive groups.Western blot experiments showed that after the application of Rigvir,the upstream protein expression of PI3K/Akt/mTOR in the sensitive cell group was significantly reduced(P<0.001).The expression levels of apoptosis factors caspase-3 and caspase-8 increased,while the Bcl-2/Bax ratio decreased(P<0.001).The results of RT-qPCR and Western blot showed that after Rigvir was applied to the sensitive cell line HT29 overexpression type,the expression levels of PI3K/Akt/mTOR upstream and downstream signaling molecules(Akt,4EBP1,and p70S6K)were significantly reduced compared to the control group(P<0.05).Conclusion:Rigvir can effectively kill some colorectal cancer cell lines(SW480,HT29)in vitro,its mechanism of action is partially in-duced by the PI3K/Akt/mTOR classical signaling pathway to induce cell apoptosis.

This article outlines the formulation process of the local standard of Traditional Chinese Medicine Chronic Disease Management Guideline for Menopausal Women with Emotional Disorders(DB44/T 2547-2024;hereafter referred to as the"Guideline").By analyzing its structural framework and content,this study elucidates the TCM-specific chronic disease management strategies incorporated in the Guidelines,aiming to supply references to the development of similar standards and provide guidance for TCM chronic disease management practices.The development for the Guideline involved a multi-dimensional evidence collection process,including literature review,summary of expert experience,and expert consultations.By employing a multi-dimensional evidence-based approach,the Guideline has effectively integrated diverse evidence sources,and ensures the standard formulation being scientific and precise.The Guideline proposes the requirements for TCM-specific chronic disease management of menopausal women with emotional disorders firstly.By incorporating TCM lifestyle regulation,TCM emotional management,TCM dietary therapy,medication guidance,exercise therapies,and distinctive external treatments,the Guideline has developed into a comprehensive TCM chronic disease management system for prevention,treatment,rehabilitation and health preservation.The integrated approach effectively reduces the recurrence of emotional disorder and enhances quality of life of the patients.

Objective To screen items of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome;To provide reference for the formulation and improvement of the scheme.Methods The Delphi method was used to distribute two rounds of questionnaires to 60 experts in cerebropathy or neurology across the country.Statistical analysis was performed on the questionnaire results of the scheme's items,including the disease names,etiology and pathogenesis,syndrome characteristics,rules and regulations,representative prescriptions,acupuncture and other therapies,and preventive care.Results Totally 42 and 50 valid questionnaires were collected.The experts reached the consensus for the importance of etiology and pathogenesis,rules and regulations,acupuncture and other therapies,and preventive care.In the section on syndrome characteristics,items with low relevance or causing ambiguity were removed.Items that were no longer used in modern times and different prescriptions with the same name were removed from the representative prescriptions.The names of syndromes,rules and regulations were unified.Conclusion The experts generally reached the consensus for the importance of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome.However,there are still some limitations that require further study and discussion.

With the rapid development of information technology， research on ancient TCM books has shifted from the traditional collation and digitization into intelligent knowledge service， thereby achieving the deep integration of ancient TCM books collation and clinical needs. Based on the clinical problem and knowledge element theory， we implemented in-depth indexing and knowledge mining for 600 kinds of ancient TCM books， built a knowledge sharing service platform for ancient TCM books by integrating database， cloud platform， knowledge graph and other technologies， and carried out the thematic literature research and developed databases for four major diseases including stroke， heart failure， liver cirrhosis， and diabetes. The digital intelligence products have been applied in hundreds of hospitals for evaluation and feedback. Finally， through "digital processing plus intelligent application"， the two-way interaction between ancient TCM books and current clinical practice is realized， and the path and paradigm of ancient TCM books knowledge serving the modern prevention and control of major diseases is formed， providing reference for the innovative utilization of ancient TCM books.

Objective To explore the current research status and frontier hotspot of task-state functional magnetic resonance imaging(fMRI)based on language task in the field of neuropsychiatric diseases. Methods Literature about the application of task-state fMRI based on language task in neuropsychiatric disorders was re-trieved from CNKI,VIP and Web of Science Core Collection databases up to November 12nd,2023.The includ-ed literature was analyzed using CiteSpace and VOSviewer. Results A total of 91 literatures were included.The researches about application of task-state fMRI based on language task in the field of neuropsychiatric disorders were reported since 2002,and developed uniformly;particularly for the diagnosis and treatment of stroke,brain tumors,epilepsy,schizophrenia and other neuropsychiatric disorders,as well as in studies of brain functional connectivity.Research hotspots included mechanisms of aphasia recov-ery,brain functional changes,functional connectivity and language laterality.Journals of psychology,education and sociology played the core role,disciplines such as neurology also contributed to the advancement of this tech-nology. Conclusion Task-state fMRI based on language task demonstrates significant potential in elucidating the mechanisms of how the brain processes language in neuropsychiatric disorders.

ObjectiveTo explore the current status and frontier hotspots of functional near-infrared spectroscopy (fNIRS) in the field of stroke. MethodsRelevant literature on stroke and fNIRS from the Web of Science Core Collection (WoSCC) database was searched from its inception to July, 2023. VOSviewer, CiteSpace and Scimago were utilized for analysis of publication output, countries (regions) and institutions, international collaboration, co-cited references, co-occurring keywords and burst keywords. ResultsA total of 379 articles were included. The research activity in this field showed an overall upward trend with slight fluctuations in the early stage. Among the top five institutions by publication output, four were from China. Co-occurrence analysis revealed that Beihang University and Boston Children's Hospital were central in collaboration networks. This study involved 1 787 authors, with 120 core authors, in which the top five most cited authors were Li Zengyong, Li Wenhao, Huo Congcong, Dou Zulin and Song Ying. The publications in this field were primarily concentrated in disciplines such as neurology, psychiatry, ophthalmology and clinical medicine. Overlay visualization of journal co-citation networks demonstrated associations between medical, clinical, and neurology disciplines with psychology, education, and sociology. Co-occurrence and clustering analysis of keywords indicated research emphasis on stroke rehabilitation, integration of multiple technical modalities, and exploration of innovative training strategies and brain activation connectivity. The research evolution of fNIRS in the stroke domain revealed initial use of photodiode devices for cerebral ischemia reperfusion monitoring. Subsequent studies refined cortical activation through improved laser sources, avalanche photodiodes, single-task experimental designs and transcranial direct current stimulation. Later, research extended to whole-brain detection, multimodal stimulation and the combination of virtual reality technology with audiovisual stimulation, resulting in significantly enhanced brain activation. The application of brain-computer interface technology further facilitated direct restoration of motor function. ConclusionResearches in the field of stroke using fNIRS technology overall demonstrat a continuous upward trend. The researches focuse on post-stroke rehabilitation, integrating multimodal fusion, brain-computer interfaces, virtual reality, and sensory stimulation for real-time monitoring and personalized neurorehabilitation training strategies. It emphasizes interdisciplinary collaboration, expanding innovative research and the application of new technologies.

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.