Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

Objective To investigate the role and underlying mechanism of C1q-like protein 4 (C1ql4) in regulating the characteristics of breast cancer stem cells. Methods qRT-PCR was used to detect the expression of C1ql4 in breast cancer and normal breast epithelial cell lines, as well as to verify the transfection efficiency of C1ql4. Western blot analysis was employed to examine the phosphorylation levels of AKT, IKK, and IκB in different groups. An AKT activator was added to MDA-MB-231 cells with C1ql4 knockdown, whereas inhibitors targeting AKT, IKK, IκB, and NF-κB nuclear translocation were separately introduced to C1ql4-overexpressing MCF-7 cells. The nuclear translocation of NF-κB, expression levels of the target genes TNF-α and IL-1β, formation ability of tumorspheres, and proportion of CD44⁺/CD24^−/low stem-like subgroups were analyzed. Results C1ql4 expression in breast cancer cell lines was significantly upregulated compared with that in normal breast epithelial cells. Western blot analysis showed that p-AKT/AKT, p-IKK/IKK, and p-IκB/IκB ratios markedly reduced in C1ql4-knockdown MDA-MB-231 cells (all P<0.05) but significantly increased in C1ql4-overexpressing MCF-7 cells (all P<0.05). Rescue experiments demonstrated that the addition of an AKT activator to C1ql4-knockdown MDA-MB-231 cells resulted in the enhanced nuclear translocation of NF-κB, the increased nuclear/cytoplasmic NF-κB ratios, the elevated TNF-α and IL-1β expression levels, and significant recovery of tumorsphere formation ability and the proportion of CD44⁺/CD24^−/low stem-like subpopulations (all P<0.05). Conversely, in C1ql4-overexpressing MCF-7 cells, treatment with AKT, IKK, IκB, or NF-κB nuclear translocation inhibitors led to a reduction in NF-κB nuclear translocation, decreased nuclear/cytoplasmic NF-κB ratios, and declines in TNF-α and IL-1β expression levels, tumorsphere formation ability, and the CD44⁺/CD24^−/low subpopulation (all P<0.05). Conclusion C1ql4 promotes the translocation of NF-κB from the cytoplasm to the nucleus through the PI3K/AKT/NF-κB signaling pathway and enhances the expression of stemness in breast cancer cells.

ObjectiveTo systematically investigate the identification characteristics of medicinal amber， elucidate its microscopic features， crystal structural properties， and elemental composition， and thereby provide a scientific foundation for quality control and authenticity verification. MethodsThirty-nine batches of amber samples were collected and analyzed through integrated techniques including morphological analysis， microscopic identification， powder X-ray diffraction （XRD）， Raman spectroscopy， Fourier-transform infrared （FTIR） spectroscopy， and inductively coupled plasma mass spectrometry （ICP-MS） to evaluate their morphological attributes， phase composition， molecular vibrational modes， and trace element profiles. Among them， the XRD experiment used Cu Kα radiation （λ=1.540 6 Å）， with a scanning angle range of 10° to 70° （2θ） and a step size of 0.02°， the Raman spectroscopy experiment employed a 785 nm laser， with a spectral measurement range of 3 400 to 50 cm^-1， a laser power of 300 mW， a laser intensity of 30%， and a scanning time of 100 to 1 000 ms， the infrared spectroscopy experiment used a carbon-sulfur lamp， with a scanning range of 4 000 to 500 cm^-1， a resolution of 4 cm^-1， and 3 scans， the ICP-MS experiment utilized frequency power of 1.2 kW， a double-pass cyclonic spray chamber， a sample introduction system flow rate of 0.7-1.0 L·min^-1， and an auxiliary gas flow of 0.2 L·min^-1. ResultsUnder orthogonal polarized light microscopy， medicinal amber exhibited an isotropic homogeneous structure， with partial samples containing inorganic impurities such as AsS and SiO₂. FTIR spectra revealed characteristic absorption peaks at 2 932-2 939 cm^-1 （C-H stretching vibrations）， 1 705-1 728 cm^-1 （C=O stretching vibrations）， and 880-887 cm^-1 （C=C deformation vibrations）， confirming the oxidative polymerization of terpenoid resin. Raman spectroscopy further identified distinctive peaks at 2 925 cm^-1， 2 870 cm^-1 （saturated C-H stretching）， and 1 648 cm^-1 （C=C stretching）， consistent with the structural features of oxidized-polymerized resin. ICP-MS analysis demonstrated that S， Al， Si， Fe， Na， and Ca were the predominant trace elements in medicinal amber. ConclusionThis study comprehensively evaluated medicinal amber's morphological attributes， phase composition， molecular vibrational modes， and trace elements through multimodal analytical techniques. The findings establish data support for establishing quality standards for medicinal amber and distinguishing it from synthetic resin imitations.

ObjectiveTo systematically investigate the identification characteristics of medicinal amber， elucidate its microscopic features， crystal structural properties， and elemental composition， and thereby provide a scientific foundation for quality control and authenticity verification. MethodsThirty-nine batches of amber samples were collected and analyzed through integrated techniques including morphological analysis， microscopic identification， powder X-ray diffraction （XRD）， Raman spectroscopy， Fourier-transform infrared （FTIR） spectroscopy， and inductively coupled plasma mass spectrometry （ICP-MS） to evaluate their morphological attributes， phase composition， molecular vibrational modes， and trace element profiles. Among them， the XRD experiment used Cu Kα radiation （λ=1.540 6 Å）， with a scanning angle range of 10° to 70° （2θ） and a step size of 0.02°， the Raman spectroscopy experiment employed a 785 nm laser， with a spectral measurement range of 3 400 to 50 cm^-1， a laser power of 300 mW， a laser intensity of 30%， and a scanning time of 100 to 1 000 ms， the infrared spectroscopy experiment used a carbon-sulfur lamp， with a scanning range of 4 000 to 500 cm^-1， a resolution of 4 cm^-1， and 3 scans， the ICP-MS experiment utilized frequency power of 1.2 kW， a double-pass cyclonic spray chamber， a sample introduction system flow rate of 0.7-1.0 L·min^-1， and an auxiliary gas flow of 0.2 L·min^-1. ResultsUnder orthogonal polarized light microscopy， medicinal amber exhibited an isotropic homogeneous structure， with partial samples containing inorganic impurities such as AsS and SiO₂. FTIR spectra revealed characteristic absorption peaks at 2 932-2 939 cm^-1 （C-H stretching vibrations）， 1 705-1 728 cm^-1 （C=O stretching vibrations）， and 880-887 cm^-1 （C=C deformation vibrations）， confirming the oxidative polymerization of terpenoid resin. Raman spectroscopy further identified distinctive peaks at 2 925 cm^-1， 2 870 cm^-1 （saturated C-H stretching）， and 1 648 cm^-1 （C=C stretching）， consistent with the structural features of oxidized-polymerized resin. ICP-MS analysis demonstrated that S， Al， Si， Fe， Na， and Ca were the predominant trace elements in medicinal amber. ConclusionThis study comprehensively evaluated medicinal amber's morphological attributes， phase composition， molecular vibrational modes， and trace elements through multimodal analytical techniques. The findings establish data support for establishing quality standards for medicinal amber and distinguishing it from synthetic resin imitations.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*

In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance

Amber and subfossil resins are subjects of interdisciplinary research across multiple fields. However, due to their diverse origins and complex compositions, different disciplines vary in their definitions and functional interpretations. In traditional Chinese medicine(TCM), amber has been utilized as a medicinal material since ancient time, with extensive historical documentation. However, its classification, provenance, and nomenclature remain ambiguous, and authentic medicinal amber artifacts are exceedingly rare. This study employed Fourier-transform infrared spectroscopy(FTIR) to characterize amber and subfossil resins from various geological sources and commercially "medicinal amber". Additionally, historical literature and market surveys were analyzed to explore their provenance, composition, and functional attributes. The results indicate that amber and subfossil resins from different sources and with different compositions exhibit distinct fingerprint characteristics in the FTIR spectral range of 1 800-700 cm~(-1). "Medicinal amber" available in the market primarily consists of subfossil or modern resins, significantly differing in composition and structure from geological amber. This study highlights the importance of interdisciplinary research on amber identification and resource management. It is essential to establish a systematic database of amber and subfossil resin characteristics and integrate modern analytical techniques to enhance research on their composition, pharmacological mechanisms, and potential therapeutic effects, thereby promoting the standardized utilization of amber resources and advancing the modernization of TCM.
Amber/history* ; Archaeology ; Spectroscopy, Fourier Transform Infrared ; Medicine, Chinese Traditional