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.

This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment"， clinical presentations often involve a complex mixture of deficiency and excess， as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing"， advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals， treatment should focus on dispersing and unblocking through modified Gegen Decoction （葛根汤）. For wind-dampness binding， it is recommended to unblock and drain， using modified Qingshang Juantong Decoction （清上蠲痛汤）. For damp-heat congestion， unblocking and clearing is the method， using modified Toufeng Shen Formula （头风神方）. For liver-gallbladder qi constraint， unblocking and soothing is the treatment principle， and modified Sanpian Decoction （散偏汤） is suggested. For insufficiency of center qi， even supplementation method is recommended， and modified Yiqi Congming Decoction （益气聪明汤） can be used. For liver yang hyperactivity， unblocking and subduing are combined， using modified Xunlong Decoction （驯龙汤）. For deficiency-cold in the liver and stomach， warming， harmonizing， unblocking， and descending are applied， using modified Wuzhuyu Decoction （吴茱萸汤）. For blood deficiency with cold congelation， unblocking and nourishing are undertaken together， using modified Danggui Sini Decoction （当归四逆汤）. The ultimate goal is to restore the dynamic balance of yin， yang， qi， and blood in the body， thereby allevia-ting pain by restoring clarity and function to the head orifices.

This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment"， clinical presentations often involve a complex mixture of deficiency and excess， as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing"， advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals， treatment should focus on dispersing and unblocking through modified Gegen Decoction （葛根汤）. For wind-dampness binding， it is recommended to unblock and drain， using modified Qingshang Juantong Decoction （清上蠲痛汤）. For damp-heat congestion， unblocking and clearing is the method， using modified Toufeng Shen Formula （头风神方）. For liver-gallbladder qi constraint， unblocking and soothing is the treatment principle， and modified Sanpian Decoction （散偏汤） is suggested. For insufficiency of center qi， even supplementation method is recommended， and modified Yiqi Congming Decoction （益气聪明汤） can be used. For liver yang hyperactivity， unblocking and subduing are combined， using modified Xunlong Decoction （驯龙汤）. For deficiency-cold in the liver and stomach， warming， harmonizing， unblocking， and descending are applied， using modified Wuzhuyu Decoction （吴茱萸汤）. For blood deficiency with cold congelation， unblocking and nourishing are undertaken together， using modified Danggui Sini Decoction （当归四逆汤）. The ultimate goal is to restore the dynamic balance of yin， yang， qi， and blood in the body， thereby allevia-ting pain by restoring clarity and function to the head orifices.

ObjectiveThis paper aims to investigate the traditional Chinese medicine syndrome types in patients with chronic hepatitis B （CHB） complicated by metabolic dysfunction-associated fatty liver disease （MAFLD） and explore the correlations between these syndrome types and clinical indicators， as well as ocular manifestation characteristics， thereby providing a reference for syndrome differentiation and treatment strategies in traditional Chinese medicine. MethodsGeneral data， information from the four diagnostic methods of traditional Chinese medicine， clinical indicators， and ocular manifestation data were collected from 506 patients with CHB complicated by MAFLD enrolled at the Public Health Clinical Center of Chengdu between June 2024 and December 2024. Cluster analysis， principal component analysis， and complex network models were employed to identify the distribution patterns of traditional Chinese medicine syndromes. Correlations between different syndrome types and clinical indicators， as well as ocular manifestation characteristics， were further analyzed. ResultsThe predominant syndromes identified in patients with CHB complicated by MAFLD were dampness and heat accumulation （51.58%）， liver depression with spleen deficiency （31.62%）， blood stasis obstructing collaterals （8.89%）， and Qi-Yin deficiency （7.91%）. No statistically significant differences were found among the four syndrome types in routine blood tests and liver function indicators. However， patients with the dampness and heat accumulation type exhibited significantly higher levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， liver stiffness measurement （LSM）， controlled attenuation parameter （CAP）， and alpha-fetoprotein （AFP）， along with lower levels of high-density lipoprotein cholesterol （HDL-C）， compared with those with other syndrome types. Regarding ocular manifestations， the incidence of moon halo signs was significantly higher in patients with the blood stasis obstructing collaterals type than in those with other syndrome types. Additionally， the incidence in scleral zone 3 （corresponding to the large intestine） was higher in patients with the damp and heat accumulation type. ConclusionDampness and heat accumulation is the core syndrome type in patients with CHB complicated by MAFLD， commonly accompanied by spleen deficiency， liver depression， blood stasis， and Yin deficiency. A complex syndrome pattern characterized by a predominance of dampness and heat， along with a mixture of deficiency and excess， is formed. Different traditional Chinese medicine syndrome types are associated with distinct clinical indicators and ocular manifestation characteristics. Among them， patients with the dampness and heat accumulation type exhibit more pronounced metabolic disturbances and liver injury， whereas those with the blood stasis type show a higher incidence of moon halo signs. Abnormalities in scleral zone 3 are also more prevalent in patients with dampness and heat type.

ObjectiveThis paper aims to investigate the distribution patterns of traditional Chinese medicine syndromes in patients with chronic hepatitis B （CHB） comorbid with metabolically associated fatty liver disease （MAFLD） and analyze their correlation with clinical characteristics and the progression of liver fibrosis. MethodsA cross-sectional study method was employed， and 506 patients with CHB comorbid with MAFLD who attended the Hepatology Outpatient Department of Public Health Clinical Center of Chengdu from June 2024 to December 2024 were enrolled. General information， traditional Chinese medicine syndromes information， laboratory indicators， and imaging examination results were collected using case report forms （CRF）. Tongue images of patients were acquired using a tongue diagnosis instrument， and tongue feature parameters were extracted using computer image processing technology. Frequency analysis， factor analysis， and cluster analysis， and other methods were used to explore syndrome categories and distribution patterns. Non-parametric tests were used to compare the differences in clinical characteristics among different syndromes. Univariate and multivariate logistic regression analyses were performed to investigate the correlation between traditional Chinese medicine syndromes and the progression of liver fibrosis. ResultsThe main traditional Chinese medicine syndromes in patients with CHB comorbid with MAFLD were mainly dominated by damp-heat accumulation syndrome， liver stagnation and spleen deficiency syndrome， and phlegm-blood stasis syndrome， with damp-heat accumulation syndrome accounting for the highest proportion （41.89%）. Compared with those without damp-heat accumulation syndrome， patients with damp-heat accumulation syndrome had significantly lower tongue proper H value， tongue coating H value， and tongue coating a^* value （P<0.05）， significantly higher tongue coating b^* value （P<0.05）， significantly increased levels of white blood cell （WBC）， red blood cell （RBC）， hemoglobin （HGB）， and glucose （GLU）， increased CAP values （P<0.05）， a higher proportion of males （P<0.05）， and a younger age （P<0.05）. Univariate and multivariate logistic regression analyses show that age， hepatitis B surface antigen （HBsAg）， diabetes， and damp-heat accumulation syndrome are independent risk factors for liver fibrosis （P<0.05）， and that damp-heat accumulation syndrome is predominantly distributed in liver fibrosis stage F0-F1. ConclusionDamp-heat accumulation syndrome is a typical syndrome in patients with CHB comorbid with MAFLD， which is significantly associated with enhanced inflammatory response， metabolic disorders， and early liver fibrosis， and is a key link in disease progression. Clinical attention and early intervention are needed.

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

" Lijie and yellowish sweating" originates from the chapter on stroke and arthralgia diseases in Synopsis of Golden Chamber. Later generations typically interpret it as yellow fluid oozing from painful joints, a characteristic manifestation of arthralgia. In Western medicine, Lijie corresponds to diseases such as gouty arthritis, with its primary clinical manifestations being redness, swelling, heat, and painful joints, most often without yellow fluid discharge. Therefore, the interpretation of " Lijie and yellowish sweating" contradicts the clinical manifestations often observed in this disease. Thus, this article reinterprets the meaning of " Lijie and yellowish sweating" from the pathogenesis of " sweat exposure to water, as if water harms the heart" , combined with the viewpoints of other medical practitioners. Determining the meaning of " yellowish sweating" is crucial for understanding the pathogenesis of arthralgia and clarifying the relationship between arthralgia and yellowish sweating. ZHANG Zhongjing mentioned arthralgia and " yellowish sweating" together, not to differentiate between the two diseases but to emphasize the common pathogenesis of the two, namely, the cold and dampness injuring the heart, blood, and vessels. This paper proposes a new explanation of " Lijie and yellowish sweating" , which suggests that " yellowish sweating" is not confined to the joints but can be found all over the body. The pathogenesis of " Lijie and yellowish sweating" lies in the insufficiency of the liver and kidney and exogenous water dampness, leading to disharmony between nutrient qi and defensive qi and between yin and yang. Primary treatment should harmonize yingfen and weifen, as well as tonify and replenish the liver and kidney. The clinical selection of medicines can be considered Guizhi Decotion, a type of formula. The pathogenesis of " Lijie and yellowish sweating" is complex, and clinical treatment should be comprehensively considered to achieve the best therapeutic effect.

Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis