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 construct a prognostic model of centrosome amplification-related genes(CARGs)by machine learning and evaluate its prediction performance for the prognosis of esophageal squamous cell carcinoma(ESCC).Methods CARGs were obtained from Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)datasets.The RNA-sequencing(RNA-seq)transcriptome datasets of ESCC were retrieved from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),and assigned into training and validation sets,respectively.Subsequently,single-sample gene set enrichment analysis(ssGSEA)and weighted gene co-expression network analysis(WGCNA)were employed to screen CARGs.A prognostic model of CARGs was constructed by incorporating 12 machine learning algorithms,and univariate and multivariate Cox regression analyses were applied to evaluate whether the 12 models as an independent prognostic factor or not.Eventually,15 paired ESCC and adjacent non-tumor tissue samples were collected from the Department of Gastroenterology of the Second Affiliated Hospital of Army Medical University,and real-time quantitative PCR(RT-qPCR)and immunohistochemistry staining were performed to detect the expression of these genes ESCC samples.Results Our 9-CARGs prediction model for ESCC prognosis was constructed.RT-qPCR confirmed that the mRNA expression levels of DENR,TRIP13,BRCA2,TTF2,TCFL5 and NUP188 were significantly higher in ESCC tissues than normal tissues(P<0.05),and the protein levels of DENR,TRIP13,TTF2 and TCFL5 were also elevated when compared to normal tissues.Conclusion DENR,TRIP13,TTF2 and TCFL5 are highly expressed and closely associated with poor prognosis of ESCC,suggesting their potential roles in the pathogenesis and progression of this malignancy.

Background and aims:Hepatocellular carcinoma(HCC)is a malignant tumor with a high mortality rate,but there are still no effective treatments.The aim of this study was to investigate the anticancer po-tential of the combined use of brefeldin A(BFA)and tunicamycin(TM)in HepG2 cells,as well as the underlying mechanisms.Methods:HepG2 cells were treated with different concentrations of BFA(0.1-2.5 mg/L)and TM(1-5 mg/L)for 24 h.DMSO(0.1％,v/v)was used as a vehicle control.Cell viability and cell migration were measured using MTT assay and scratch wound assay,respectively.Apoptosis was detected using flow cytometry and acridine orange(AO)staining.The protein and mRNA levels of various factors involved in apoptosis(poly(ADP-ribose)polymerase-1(PARP-1),caspase-12,caspase-3,and stearoyl-CoA desaturase 1)and endoplasmic reticulum(ER)stress(binding immunoglobulin protein(BiP),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,phosphorylation of eukaryotic translation initiation factor 2alpha(p-eIF2α),activating transcription factor(ATF)4,and C/EBP homologous protein(CHOP))were measured using Western blotting and qRT-PCR,respectively.Results:Both BFA and TM alone significantly reduced the viability of HepG2 cells in a dose-dependent way.The co-incubation with TM(1 mg/L)further significantly reduced the viability of HepG2 cells treated with BFA(0.25 mg/L)alone(P＜0.05).BFA significantly increased the protein and mRNA levels of caspase-3 and PARP-1(P＜0.05)compared to control and DMSO-treated cells,indicating that BFA induced apoptosis in HepG2 cells by increasing the expression of caspase-3 and PARP-1.The induction of apoptosis by BFA could be further significantly enhanced by co-incubation with TM.In addition,BFA significantly increased the mRNA levels of BiP,PERK and ATF4(P＜0.05)compared to control and DMSO-treated cells.After co-incubation of BFA and TM,the protein levels of BiP,p-PERK,p-eIF2α and CHOP were significantly increased,indicating that TM could enhance BFA-induced ER stress in HepG2 cells through the PERK-eIF2α-ATF4-CHOP pathway.Conclusions:BFA could induce apoptosis and ER stress,and TM could enhance the ability of BFA to induce apoptosis and ER stress in HepG2 cells through the PERK-eIF2α-ATF4-CHOP pathway.The findings highlight the therapeutic potential of the combined use of BFA and TM in treating HCC.

Wuhutang is the 51st Chinese medicine prescription of Han ethnic group on in the catalogue of ancient classical prescriptions （the second batch） ，which originated from Renzhai' Straight Diections Prescriptions （《仁斋直指方》） by YANG Shiying in the Song dynasty，it is composed of 5 medicines， including Ephedrae Herba，Armeniacae Semen Amarum， Glycyrrhizae Radix et Rhizoma， tea and Gypsum Fibrosum. It treats shortness of breath and phlegm. Following the principle of textual research on the key information of ancient classical famous prescriptions， the author collected and recorded the ancient books of traditional Chinese medicine of Wuhutang with the method of Bibliometrics， and screened out 53 valid data， involving 41 ancient books. Based on the historical evolution， drug composition， main treatment of disease and syndrome， drug dosage， method of preparation and usage， drug origin and processing， the author conducted a dig and a systematic study of Wuhutang. The results show that：in the later generations， besides inheriting the original prescription， the composition of medicine was added or subtracted， and the frequency of addition of Mori Cortex was the most；in the treatment of disease and syndrome， most of them inherited the original prescription mainly treating asthma syndrome， also see in the treatment of asthma， cough and other lung disease， in the drug dosage and method of use ， it is suggested to inherit the original prescription， the dosage of each medicine is： Ephedrae Herba 2.89 g， Armeniacae Semen Amarum 4.13 g， Glycyrrhizae Radix et Rhizoma 1.65 g， tea 3.30 g， Gypsum Fibrosum 6.20 g， decoction， take warm clothes before eating；on the source of medcine，ephedra is made from the dried herbaceous stems of Ephedra sinica （Ephedraceae），bitter almond is made from the dried and mature seeds of Prunus armeniaca （Rosaceae），Licorice is made from the dried roots and rhizomes of Glycyrrhiza uralensis（Legumes）， tea is made from the buds leaves of Camellia sinensis（Camellia），plaster is made from Gypsum Fibrosum of sulfate mineral gypsum family. At the same time， we collected and sorted the modern clinical application literature of Wuhutang， and obtained 73 effective literatures， all of which are for the treatment of respiratory system diseases， especially for children's pneumonia and asthma， and mostly belong to"phlegm-heat obstructing the lung syndrome". Through the analysis and study of ancient books and modern applied literature， the historical evolution and prescription evolution of Wuhutang are clarified， and its key information is determined， in order to provide more accurate reference for the research and development of the classic Wuhutang and the rational addition and subtraction of the application.

The classic formula Wuyaotang is the 49^th of the 100 formulas in the Catalogue of Ancient Classic Prescriptions (First Batch) issued by the National Administration of Traditional Chinese Medicine, and is from the Secrets from the Orchid Chamber (《兰室秘藏》) by LI Dongyuan of the Jin Dynasty. It is composed of Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Linderae Radix, and Cyperi Rhizoma, and has the effect of moving Qi, regulating meridians, and relieving pain. It is mainly indicated for Qi stagnation and blood stasis syndrome. Based on the ancient books on Wuyaotang, this study systematically reviewed the formula source, composition, dosage, preparation, usage, functions, indications, preparation principle, drug processing, modification, etc. of Wuyaotang with the bibliometrics method, explored its historical evolution, and determined the key information. Statistical analysis of its modern literature shows that there are few studies of the original formula of Wuyaotang, and the clinical studies mainly focus on modified Wuyaotang. It has a wide range of treatment scope and can be used for the treatment of dysmenorrhea, delayed menstrual cycle, hypomenorrhea, and menstrual fever, as well as ulcerative colitis, spleen distortion, sciatica, child intestinal spasm, and other internal, surgical, gynecological, and pediatric diseases. The pathogenesis in traditional Chinese medicine (TCM) is Qi stagnation. Through the analysis and research on ancient books and modern literature recording Wuyaotang, this study is expected to provide a scientific basis for the clinical application, in-depth research, and development of the classic formula Wuyaotang.

Objective To investigate whether BPA and its substitutes BPAF,BPB,and BPS can induce lipid accumulation in hepato-cytes.Methods HL-7702 cells were treated with BPA,BPAF,BPB,or BPS for 24 h.Lipid droplet accumulation in cells was observed via oil red O staining,and triglyceride content was determined through the GPO-PAP chemical-enzymatic method.In addition,qRT-PCR was used to detect the expression of triglyceride synthesis-related genes.Results Red lipid droplets of different sizes could be observed in the BPA,BPAF,BPB,and BPS groups.The intracellular triglyceride content increased significantly under 1 and 50 μmol/L BPA,10 and 50μmol/L BPAF,1,10,and 50μmol/L BPB,and 50μmol/L BPS.LIPIN2 mRNA expression level increased significantly under 10μmol/L BPAF,10μmol/L BPB,and 1 and 10μmol/L BPS.DGAT2 mRNA expression increased significantly under 50μmol/L BPA,10μmol/L BPAF,10 and 50μmol/L BPB,and 1μmol/L BPS.Conclusion BPAF,BPB,and BPS can increase intracellular triglyceride synthesis by upregulating LIPIN2 and DGAT2 mRNA expression,leading to intracellular fat accumulation and increased triglyceride con-tent in HL-7702 cells.

Danggui Liuhuangtang is the 47^th of the 100 famous classical formulas published by the National Administration of Traditional Chinese Medicine， and is known as the holy medicine for night sweat. By bibliometrics， the authors collected the ancient books on Danggui Liuhuangtang and screened out 269 valid data， involving 156 ancient books of traditional Chinese medicine. The analysis on the historical origin， disease syndromes， pathogenesis， composition， dosage， preparation， usage， and processing of Danggui Liuhuangtang found that this famous classical formula originated from Secret Book of the Orchid Chamber （《兰室秘藏》） written by LI Dongyuan， and is composed of Angelicae Sinensis Radix， Rehmanniae Radix， Rehmanniae Radix Praeparata， Phellodendri Chinensis Cortex， Scutellariae Radix， Coptidis Rhizoma and Astragali Radix. It has the functions of nourishing Yin， reducing fire， consolidating exterior and stopping sweating， and mainly treats night sweat due to Yin deficiency and fire exuberance. In the later generations， disease syndromes are mostly treated based on LI Dongyuan's theory， and have expanded to more than 30 kinds （339 in total）， among which night sweat （208） was the most， accounting for 61.36% of the total disease syndromes， followed by spontaneous sweating （38）， accounting for 11.21%. Additionally， it was found that Danggui Liuhuangtang was widely used in modern clinical practice for various disease syndromes. Among them， endocrine disease （77， 28.21%） was predominant， followed by gynecological disease （48， 17.58%）， and pediatric disease （24， 8.79%）. Although Danggui Liuhuangtang treats many disease syndromes， their pathogenesis was always yin deficiency and fire exuberance. Through the systematic excavation of the ancient books on Danggui Liuhuangtang and the analysis of its modern clinical application， this paper probed into the historical evolution and confirmed the key information of the formula， providing detailed literature basis for the research and development application of famous classical formulas.

Shengyang Yiweitang is one of the first 100 classical prescriptions published by the National Administration of Traditional Chinese Medicine. It originated from the Clarifying Doubts about Damage from Internal and External Causes by physician LI Dongyuan of Jin dynasty， and is composed of Astragali Radix， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Pinelliae Rhizoma， Citri Reticulatae Pericarpium， Angelicae Pubescentis Radix， Saposhnikoviae Radix， Notopterygii Rhizoma et Radix， Bupleuri Radix， Paeoniae Radix Alba， Alismatis Rhizoma， and Coptidis Rhizoma. With the effects of replenishing Qi， promoting Yang， clearing heat and removing dampness， Shengyang Yiweitang is used to treat spleen-stomach weakness and dampness-heat accumulation syndrome. Using bibliometrics， the authors systematically sorted out the source，composition， dosage， preparation， efficacy， indications， principle of composition， origin and processing of drugs，and modern clinical application of the prescription， and explored its history and key information. Additionally， it was found that Shengyang Yiweitang was widely used in modern clinical practice and was suitable for multisystem diseases， of which digestive system （264） was the most common， accounting for 41.71%， followed by urogenital system （57， 9.00%） and nervous system （48， 7.58%）. Although the treatment scope was wide， the pathogenesis of the diseases in traditional Chinese medicine belongs to "spleen-stomach weakness"， which fully reflected Li's academic thought of "internal injury of spleen and stomach leads to various diseases". The key information of Shengyang Yiweitang was determined by summarizing the relevant ancient books and modern literature， so as to provide accurate reference for its rational clinical application and further research and development.

Qingweisan is one of the classical prescriptions commonly used in the treatment of oral diseases. By means of Bibliometrics， the authors collected the ancient books on Qingweisan and sifted out 411 valid data， involving 116 classics of traditional Chinese medicine. The historical origin， drug composition， indications， principle of composition， dosage，and preparation of Qingweisan were statistically analyzed， and it was found that the prescription originated from the Treatise on Spleen and Stomach（《脾胃论》） by LI Dongyuan and is composed of Rehmanniae Radix， Angelica Sinensis， Cortex Moutan， Coptidis Rhizoma and Cimicifugae Rhizoma， with the functions of clearing stomach， purging fire， cooling blood and dispersing depression. And Qingweisan was mainly used to treat toothache， headache， and preference for cold and aversion to heat caused by "excessive heat in yang brightness meridian". There were 352 indications recorded， most of which followed LI Dongyuan's theory and the expanded indications reached 70 kinds. Specifically， toothache （132） was the most， accounting for 22.49% of the total indications， followed by headache （60， 10.22%）. In addition， Qingweisan was widely used in modern clinical practice for multiple system diseases， among which oral system （197） was dominant， accounting for 72.69%， followed by skin system （28， 10.33%） and digestive system （27， 9.96%）. Although the indications were wide， the pathogenesis always belonged to "upward attack of stomach fire". Through the excavation and statistical analysis of the ancient books on Qingweisan and its modern clinical application， the authors aimed to provide a more scientific reference for the research and application of classical famous prescriptions.