LIU Wansu， as the foremost of the four great masters of the Jin-Yuan period， established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke， thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background， academic origins， and core connotations of its theoretical construction. The study found that， based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic （Huang Di Nei Jing） and combined with clinical practice， LIU Wansu proposed that fire-heat is the fundamental cause of stroke， and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire， emphasizing differentiated treatment of exterior and interior syndromes， Six Meridians syndrome differentiation， and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period， but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi， thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine （TCM）. Modern pharmacological research provides solid scientific evidence， confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses， oxidative stress， and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents， such as Huanglian Jiedu Tang and baicalin， can exert multi-target neuroprotective effects by regulating inflammatory signaling， enhancing antioxidant enzyme activity， and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis， and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.

LIU Wansu， as the foremost of the four great masters of the Jin-Yuan period， established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke， thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background， academic origins， and core connotations of its theoretical construction. The study found that， based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic （Huang Di Nei Jing） and combined with clinical practice， LIU Wansu proposed that fire-heat is the fundamental cause of stroke， and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire， emphasizing differentiated treatment of exterior and interior syndromes， Six Meridians syndrome differentiation， and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period， but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi， thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine （TCM）. Modern pharmacological research provides solid scientific evidence， confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses， oxidative stress， and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents， such as Huanglian Jiedu Tang and baicalin， can exert multi-target neuroprotective effects by regulating inflammatory signaling， enhancing antioxidant enzyme activity， and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis， and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.

Background: Recurrent pregnancy loss undermines the physical and mental health of women. Recent randomized controlled trials have reported some effects of traditional Chinese medicine (TCM); however, whether various TCM methods have different effectiveness remains unclear. Objective: To comprehensively evaluate the efficacy and adverse events of TCM for patients with RPL and to explore whether various TCM methods have different effectiveness. Methods: Ten databases were searched up to May 27, 2024. The risk of bias was assessed using the RoB2 tool. The certainty of the evidence was evaluated using the grading of Recommendations, Assessment, Development, and Evaluation tool. Pairwise and network analyses were conducted using Stata 18.0. Results: A total of 47 randomized controlled trials enrolling 6678 women with RPL were included. Pairwise analysis showed that use of TCM had a significantly lower miscarriage rate (RR 0.50 [95% CI 0.45, 0.55]), lower preterm birth rate (RR 0.81 [95% CI 0.67, 0.98), and lower adverse event rate (RR 0.46 [95% CI 0.37, 0.58]). Moreover, use of TCM was associated with a higher alive-fetus rate (RR 1.21 [95% CI 1.15, 1.26]), live-birth rate (RR 1.20 [95% CI 1.15, 1.25]), and full-term rate (RR 1.37 [95% CI 1.23, 1.53]) compared with nonuse of TCM. Network analysis demonstrated that Bushenshugan combined with conventional Western medicine was ranked the best for the reduction of miscarriage rate. Discussion: Use of TCM is more likely to improve pregnancy outcomes and reduce adverse events compared with nonuse of TCM in patients with RPL. Different TCM methods have differences in reducing the miscarriage rate. The Bushenshugan method might be a potential optimal TCM therapy, but more high-quality evidence is needed to further validate and evaluate the efficacy and safety.

Objective:To explore the progress and trend in research of target trial emulation (TTE) and provide reference for research in this field.Methods:A literature retrival of research papers in this field published as of November 30, 2024 was conducted based on three databases (i.e. PubMed, Web of Science, and Scopus). The papers which were highly cited were analyzed by Bibliometrix package in R 4.3.2. The co-occurrence network of keywords were analyzed by using software VOSviewer. The keyword burst test was carried out with software CiteSpace.Results:A total of 685 papers from 314 journals were included. The annual number of the papers published showed a significant growth in recent three years. JAMA Network Open had the highest publication mumber related to TTE (34 papers), Annals of Internal Medicine had the highest H-index and American Journal of Epidemiology had the highest total citations. In the 2 997 authors, Hernán MA made a greatest contribution. In the 2 046 institutions, Harvard Medical School was at leading position. The analysis on highly cited papers and keyword co-occurrence showed that TTE was mainly used in the studies of COVID-19 vaccine, cancer and the treatment efficacy and safety of chronic diseases. The analysis on the co-occurence of keyword burst test showed that keywords frequently used until 2024 were COVID-19 vaccine, cardiovascular disease and breast cancer. Conclusions:TTE is mainly used in the studies of public health emergency (such as COVID-19), patients with cancer and chronic diseases. TTE will play a crucial role when randomized controlled trial is difficult to conduct or current evidence requirement can not be met.

The culture of suspended Vero cells is facing difficulties such as low cell viability and long doubling time. To investigate the main reasons for the slow growth and low viability of suspended Vero cells, this study conducted transcriptomic analysis of suspended Vero cells (Vero-XF) and adherent Vero cells (Vero-AD) to screen the differentially expressed genes (DEGs) affecting the growth of suspended cells. In addition, epidermal growth factor (EGF) was supplemented to the culture system to improve the growth of Vero-XF. The results showed that compared with the Vero-AD group, the Vero-XF group had 7 376 significant DEGs. Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the DEGs were mainly enriched in the autophagy and mitophagy pathways. Eleven DEGs were selected and verified by quantitative real-time PCR, which showed up-regulated expression of ATG9B, WIPI2, LAMP2, OPTN, Rab7a, and DEPTOR and down-regulated expression of ATG4D, being consistent with the results of transcriptomic analysis. In addition, the Vero-XF group showed significantly up-regulated expression of ATG101, ATG2A, and STX17 and insignificant change in the expression of NBR1, compared with the Vero-AD group. The protein levels of LC3 and P62 in Vero-XF and Vero-AD were determined by Western blotting, which showed up-regulated expression of LC3Ⅱ/Ⅰ and down-regulated expression of P62 in Vero-XF, indicating a higher level of autophagy. Finally, the exogenous supplementation of EGF at 10, 20, and 30 μg/L in the culture system reduced the autophagy level of Vero-XF by 22.35%, 48.15%, and 71.29%, increased the specific growth rate by 15.48%, 33.33%, and 57.14%, and decreased the apoptosis rate by 2.84%, 15.46%, and 16.23%, respectively. The results of this study preliminarily reveal that the activation of autophagy is one of the reasons for the slow growth of Vero-XF, which provides reference for the subsequent culture of suspended Vero cells.
Animals ; Vero Cells ; Autophagy/genetics* ; Chlorocebus aethiops ; Epidermal Growth Factor/pharmacology* ; Gene Expression Profiling ; Transcriptome ; Cell Survival

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To explore the new mechanism of Escin inhibiting the progression of breast cancer cells.Methods Escin treatment groups with different concentrations(0,10,20,30,40μg/ml)were set up,and BC cells were treated with corresponding concentrations of Escin,then CCK8,clonal formation,flow cytometry,transmission electron microscopy and protein immunoblotting were used to evaluate the cell phenotype and possible mechanisms.Control group,Escin group and Escin+VX-765 group were set up,to determine the role of Caspase-1/GSDMD signaling pathway in Escin-induced pyroptosis of BC cells,cells were pretreated with Caspase-1 inhibitor VX-765.The cells in control group,Escin group and Escin+NAC group were pretreated with the reactive oxygen species(ROS)scavher N-Acetylcysteine(NAC),to determine the role of ROS in Escin induced pyroptosis of BC cells.Results Compared with the control group,different concentrations of Escin inhibited the proliferation and colony formation of BC cells in a concentration dependent manner(P＜0.05).Compared with the control group,the ROS and pyroptosis rate were increased in Escin-treated group(P＜0.05).The protein expression levels of FL-GSDMD and pro-Caspase-1 were significantly decreased in the Escin-treated group,while N-GSDMD,cleaved Caspase-1 and IL-18 protein expression were significantly increased(P＜0.05).Compared with the Escin-treated group,the proliferation rate of Escin+VX-765 group was increased(P＜0.05),and the expression of pyroptosis protein was decreased(P＜0.05).Compared with the Escin-treated group,the proliferation rate of Escin+NAC group was increased(P＜0.05),and the ROS,pyroptosis rate and pyroptosis protein expression were decreased(P＜0.05).Conclusion The inhibitory effect of Escin on the progression of breast cancer cells may be related to its regulation of ROS/Caspase-1/GSDMD signaling pathway to promote cell pyroptosis.

Objective:To explore the progress and trend in research of target trial emulation (TTE) and provide reference for research in this field.Methods:A literature retrival of research papers in this field published as of November 30, 2024 was conducted based on three databases (i.e. PubMed, Web of Science, and Scopus). The papers which were highly cited were analyzed by Bibliometrix package in R 4.3.2. The co-occurrence network of keywords were analyzed by using software VOSviewer. The keyword burst test was carried out with software CiteSpace.Results:A total of 685 papers from 314 journals were included. The annual number of the papers published showed a significant growth in recent three years. JAMA Network Open had the highest publication mumber related to TTE (34 papers), Annals of Internal Medicine had the highest H-index and American Journal of Epidemiology had the highest total citations. In the 2 997 authors, Hernán MA made a greatest contribution. In the 2 046 institutions, Harvard Medical School was at leading position. The analysis on highly cited papers and keyword co-occurrence showed that TTE was mainly used in the studies of COVID-19 vaccine, cancer and the treatment efficacy and safety of chronic diseases. The analysis on the co-occurence of keyword burst test showed that keywords frequently used until 2024 were COVID-19 vaccine, cardiovascular disease and breast cancer. Conclusions:TTE is mainly used in the studies of public health emergency (such as COVID-19), patients with cancer and chronic diseases. TTE will play a crucial role when randomized controlled trial is difficult to conduct or current evidence requirement can not be met.

Objective To explore the new mechanism of Escin inhibiting the progression of breast cancer cells.Methods Escin treatment groups with different concentrations(0,10,20,30,40μg/ml)were set up,and BC cells were treated with corresponding concentrations of Escin,then CCK8,clonal formation,flow cytometry,transmission electron microscopy and protein immunoblotting were used to evaluate the cell phenotype and possible mechanisms.Control group,Escin group and Escin+VX-765 group were set up,to determine the role of Caspase-1/GSDMD signaling pathway in Escin-induced pyroptosis of BC cells,cells were pretreated with Caspase-1 inhibitor VX-765.The cells in control group,Escin group and Escin+NAC group were pretreated with the reactive oxygen species(ROS)scavher N-Acetylcysteine(NAC),to determine the role of ROS in Escin induced pyroptosis of BC cells.Results Compared with the control group,different concentrations of Escin inhibited the proliferation and colony formation of BC cells in a concentration dependent manner(P＜0.05).Compared with the control group,the ROS and pyroptosis rate were increased in Escin-treated group(P＜0.05).The protein expression levels of FL-GSDMD and pro-Caspase-1 were significantly decreased in the Escin-treated group,while N-GSDMD,cleaved Caspase-1 and IL-18 protein expression were significantly increased(P＜0.05).Compared with the Escin-treated group,the proliferation rate of Escin+VX-765 group was increased(P＜0.05),and the expression of pyroptosis protein was decreased(P＜0.05).Compared with the Escin-treated group,the proliferation rate of Escin+NAC group was increased(P＜0.05),and the ROS,pyroptosis rate and pyroptosis protein expression were decreased(P＜0.05).Conclusion The inhibitory effect of Escin on the progression of breast cancer cells may be related to its regulation of ROS/Caspase-1/GSDMD signaling pathway to promote cell pyroptosis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.