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.

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

ObjectiveTo explore the research status and trends of cohort studies on traditional Chinese medicine （TCM） efficacy evaluation from 2017 to 2022 and provide ideas and references for research in this field. MethodsSix databases including Pubmed， Web of Science， Embase， Scopus， Cochrane Library and CNKI were searched from January 1st， 2017 to December 31st， 2022. The total number of annual publications， journals， highly cited literatures， and keywords were quantitatively and visually analyzed by Bibliometrix. ResultsA total of 328 articles were included， which were published in 141 journals. The number of articles published in this field showed an overall upward trend， and retrospective cohort studies （282 papers， 85.98%） accounted for the largest proportion. A total of 151 cohort studies （46.04%） were conducted based on the database and showed an overall upward trend. The subjects were mainly patients with tumors （77 papers， 23.48%）， and cardiovascular and cerebrovascular diseases （64 papers， 19.51%）. The top 3 highly cited literatures mainly explore the association between TCM and survival outcome and quality of life in patients with malignant tumors. Fourteen and twenty-five high-frequency keywords were included in Chinese and English literature respectively， which formed 3 clusters such as research methods， statistical analysis and diseases. ConclusionIt was the current status to focus on retrospective cohort studies and focus on patients with tumors or cardiovascular and cerebrovascular diseases. Using observational database to conduct cohort studies of TCM efficacy evaluation could be the future research direction.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Objective To compare the difference in risk of drug-induced liver injury(DILI)between Runzao Zhiyang capsules and loratadine tablets.Methods Based on electronic medical records obtained through active drug safety monitoring in China,a retrospective cohort study was conducted to collect clinical data of patients who took oral Runzao Zhiyang capsules or loratadine tablets between January 1,2004,and December 31,2021.After balancing the confounding factors with a 1∶1 propensity score,the logistic regression model was used to analyze the risk of DILI between the two groups.Additionally,the sensitivity analysis of the data before matching and after inverse probability weighting method was conducted.Results A total of 31 636 patients were included,with 26 840 patients taking Runzao Zhiyang capsules orally.After matching there were 4 072 patients in each group,the risk of DILI in the Runzao Zhiyang capsules group was significantly lower than in the loratadine tablets group(0.12％vs.0.83％),OR=0.15(95％CI 0.06 to 0.38).Before matching and after inverse probability weighting,the incidence of DILI in the Runzao Zhiyang capsules group was still lower than that in the loratadine tablets group,and the difference was statistically significant(P＜0.001).Conclusion Runzao Zhiyang capsules have a better safety profile in terms of liver injury compared to the loratadine tablets.The hepatotoxicity of Polygonum multiflorum and its preparations should be scientifically evaluated and rationally treated to ensure medication safety and health.

Objective To evaluate the correlation between residual cholesterol(RC)and pre-diabetes(Pre-DM)conversion.Methods The data of this research came from the SENSIBILE-Cohort study,which included 2741 individuals with Pre-DM and followed up for 3 years.RC=TC-HDL-C-LDL-C.Logistic regression analysis was used to identify the factors influencing the progression of Pre-DM to DM and the return to normal blood glucose,while multiple linear regression analysis was used to identify the influencing factors for RC.Results During a 3-year follow-up period,1659 cases(60.5%)of the Pre-DM population maintained Pre-DM status,351 cases(12.8%)progressed to DM,and 731 cases(26.7%)returned to normal blood glucose.Logistic regression analysis showed that when defining Pre-DM according to ADA diagnostic criteria,high RC was the influencing factor for Pre-DM progression to DM and return to normal BG in the unadjusted model.After adjusting for age,gender,nationality,BMI,SBP,smoking,drinking,SUA,TG,exercise and meat diet,high RC may reduce the likelihood of Pre-DM returning to normal blood glucose,but RC is not a contributing factor to the progression of Pre-DM to DM.Multiple linear regression analysis shows that SBP,DBP,2 hPG,triglyceride/glucose index,Chinese visceral fat index,and lipid accumulation products are the influencing factors for RC.Conclusions High RC reduces the likelihood of Pre-DM returning to normal blood glucose.RC is not a contributing factor to the progression of Pre-DM to DM.

Screening for diabetes and its complications contributes to slowing the progression of diabetes mellitus. Based on the setting of grass-roots diabetes complication screening workstation with the concept of two stages of screening and three levels of prevention, we proposed a hospital-community-family integrated diabetes management strategy. This article discusses the background, organization structure, operation mechanism and implementation process of this strategy, aiming to provide reference for constructing a suitable and practical grass-roots diabetes management model.

Objective:Evaluate the safety and efficacy of aortic endovascular remodeling device (AERD) in the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair.Methods:Adopting a prospective cohort study design, according to the inclusion and exclusion criteria, a total number of 60 patients with Stanford B-type aortic dissection after TEVAR surgery from January 2022 to December 2023 were included. Collecting CTA imaging data of patients before and after endovascular treatment with AERD and using computer 3D reconstruction fluid dynamics to evaluate distal aortic remodeling.Results:The incidence of major adverse events and mortality rate associated with aortic dissection within 30 days were 0 after endovascular treatment with AERD. In the short term, AERD was safe for the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair. Endovascular treatment with AERD significantly increased the volume of the true lumen of the aorta in the dissection segment, with an increase of 88.44%. At the same time, endovascular treatment with AERD significantly reduced the volume of the false lumen of the aorta in the dissection segment, with a decrease of 61.04%. Endovascular treatment with AERD has no significant effect on the longest true lumen diameter of distal aorta of stent and upper margin aorta of superior mesenteric artery. Comparing to the longest diameter of the true lumen of the aorta, the change in the shortest diameter of the true lumen of the aorta is more significant, with the shortest diameter of true lumen of distal aortic of the stent increasing by 32.29%, the shortest diameter of true lumen of the narrowest part of the aorta increasing by 204.15%, the shortest diameter of true lumen of the upper margin aorta of superior mesenteric artery increasing by 80.76%, the shortest diameter of true lumen of the lower edge aorta of the renal artery increasing by 115.26%, the shortest diameter of the opening of the left iliac artery increasing by 152.01%, and the shortest diameter of opening of the right iliac artery increasing by144.21%.Conclusion:AERD is safe and effective in the treatment of residual aortic dissection on Stanford type B aortic dissection patients after endovascular repair. Endovascular treatment with AERD promotes true lumen dilation and false lumen reduction in the early postoperative stage and promotes benign remodeling of the distal aorta after TEVAR surgery.