ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties， this paper systematically contrasted the quality differences between wild Polygalae Radix（WPR） and cultivated Polygalae Radix（CPR） from the aspects of character， microscope and chemical composition by modern scientific and technological means， providing a basis for high-quality production and quality control. MethodsCPR and local WPR in Yulin city， Shaanxi province from 1 to 6 years were collected， and a systematic comparative analysis was conducted using traditional pharmacognosy research methods combined with modern multi-omics analysis techniques， including character traits（length， weight， diameter）， cross-sectional microscopic features（proportions of cork， phloem， xylem， etc）， cell wall component content（hemicellulose， cellulose， lignin）， extracts content（water-soluble extract and alcohol-soluble extract）， carbohydrate content（starch， water-soluble polysaccharides）， contents of total flavonoids， total saponins and specific marker compounds（3，6′-disinapoyl sucrose， polygalaxanthone Ⅲ， tenuifoliside A， tenuifoliside C， sibiricose A₅ and A₆） and other indexes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to conduct comparative analysis of secondary metabolites in WPR and CPR， and multivariate statistical analysis such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to screen the key differential components of them. ResultsIn terms of appearance， there were significant differences between WPR and CPR. The characteristics of WPR conformed to the "thick wrinkles on the epidermis" recorded in ancient books， featuring a wrinkled surface and grayish-brown appearance. However， CPR had a finer texture and a yellowish white appearance， with weight， length， and diameter increasing with longer cultivation periods. In terms of microscopy， WPR exhibited a thick cork layer with fissures in the phloem， whereas CPR had a thinner cork layer with uniformly arranged cork cells. Younger PR specimens showed numerous phloem fissures in cross-sections， while older specimens display progressively denser arrangements of phloem parenchyma cells. In terms of the contents of various major components， the contents of water-soluble extract， starch and total saponins in WPR were inversely proportional to the root diameter， while the contents of water-soluble extract， water-soluble polysaccharides and total saponins in CPR decreased with the increase of planting years. The content of xanthones in WPR was significantly higher than that of CPR， while the contents of other major components showed no significant change pattern. Among the six indicator components， the average content of sibiricose A₅ in WPR was significantly higher than that of CPR， followed by slightly higher content of tenuifoliside A. In CPR， the relative content of 3，6′-disinapoyl sucrose and tenuifoliside A was the highest. The former showed an increase in volatility with increasing cultivation years， while the latter showed a decrease in volatility. The results of differential compound analysis based on UPLC-Q-TOF-MS showed that there were significant differences in metabolites between WPR and CPR samples. Among them， the seven compounds with the largest differences among WPR samples of different thicknesses were polygalasaponins， and for CPR with different planting years， the main differential compounds were oligosaccharide esters. ConclusionThere are differences between WPR and CPR in character， microscopic structure and chemical composition， and some components are inversely proportional with the increase of diameter and cultivation duration due to the distribution characteristics. However， the longer the cultivation years of PR， the closer it is to the "thick wrinkles on the epidermis" of WPR， which has been respected by generations. It is suggested that this traditional character combined with modern component contents should be used as the index of artificial cultivation and quality control of PR.

This article systematically analyzed the historical evolution of the name， origin， harvesting and others of Longan Arillus by referring to the ancient and modern literature， in order to provide a foundation for developing famous classical formulas containing this herb. After textual research， it indicated that Longan Arillus was first recorded under the name of longan in Shennong Bencaojing of the Han dynasty. During the Ming and Qing dynasties， Longan Arillus gradually replaced longan as the standard name recorded in the materia medica， with additional aliases including Yizhi， Lizhinu and Yuanyan. The source of Longan Arillus used in the past dynasties was the arillus of the Sapindaceae plant Dimocarpus longan. The production regions recorded in the past dynasties were mainly Fujian， Guangdong， Guangxi， Hainan， Sichuan and others. Since the Qing dynasty， Longan Arillus produced in Fujian， Guangdong and Guangxi have been regarded as the finest and authentic varieties， with Fujian， Guangxi， and Guangdong remaining the primary authentic production areas today. In ancient times， the fruits were primarily harvested in August of the lunar calendar. However， modern longan cultivation typically involves harvesting ripe fruits during summer and autumn. Post-harvest processing involves removing moisture through sun-drying or baking before drying for medicinal use. Throughout history， processing methods have primarily focused on raw product， though techniques such as wine soaking and powdering have also been employed. Since modern times， it has been concluded that its quality is the best one with thick flesh， sweet taste， brownish-yellow color and tender texture. Longan Arillus possesses a sweet and warm nature， entering the heart and spleen meridians. Its primary functions are tonifying the heart and spleen， nourishing the blood and calming the spirit， which is consistent in ancient and modern times. Based on the textual research， it is suggested to use the arillus of D. longan when developing the famous classical formulas containing Longan Arillus. Processing methods should be selected according to the formula requirements， where no specific processing is indicated， the raw products is recommended for medicinal use.

This article systematically reviews and examines the historical evolution of Bambusae Succus as a medicinal material， covering aspects such as nomenclature， origin， geographical distribution， harvesting and processing methods， quality assessment， therapeutic effects and indications， by consulting ancient herbal texts， medical compendia， and modern literature. The aim is to provide a reference for the development and utilization of famous classical formulas containing this herb. Research indicated that Bambusae Succus was first documented in the Shennong Bencaojing during the Han dynasty， with Zhuli being the standard name used throughout history， alongside aliases like Zhuzhi， Zhuyou and Huoquan. Historically， the primary source of Bambusae Succus has been Phyllostachys nigra var. henonis（Danzhu）， although other species such as Pleioblastus amarus and Bambusa emeiensis have also been used medicinally. Ancient records predominantly noted its origin in Yizhou（present-day Chengdu and surrounding areas in Sichuan） and the Wuling region（between present-day Hunan， Guangdong， Guangxi and Jiangxi provinces）， while contemporary sources are mainly from regions south of the Yangtze River and southwestern China. Traditionally， Bambusae Succus was harvested from bamboo that had grown for exactly one year， today， it can be collected year-round without strict age requirements. Ancient preparation methods included direct fire roasting or dry distillation， whereas modern industrial production employs dry distillation， reflux extraction， and percolation. In terms of quality evaluation， ancient texts considered a sweet taste to be superior， while today， clarity and transparency are prioritized. Historically， Bambusae Succus was characterized as sweet and cold nature， targeting the lung and stomach meridians， with uses evolving from clearing heat and resolving phlegm to nourishing Yin， moistening dryness， and relaxing tendons and unblocking meridians. Modern descriptions classify it as sweet， bitter， and cold in nature， affecting the heart， liver， and lung meridians， with functions including clearing heat， resolving phlegm， and facilitating orifices. It is indicated for conditions such as stroke with phlegm confusion， lung heat with phlegm congestion， convulsions， epilepsy， excessive phlegm in febrile diseases， high fever with thirst， irritability during pregnancy， and tetanus， with more clearly defined applications. Based on the results of the research， it is recommended that when developing and utilizing famous classical formulas containing Bambusae Succus， the one-year-old Phyllostachys nigra var. Henonis， which has been highly praised throughout history， should be selected as the source material. Industrial production should adopt the dry distillation method. Furthermore， in-depth research should be conducted on the modern technological characterization of the traditional quality control indicator of sweet taste， and reasonable modern quality control standards should be established.

By consulting ancient and modern literature， this article systematically reviews and verifies the historical evolution of the herbal medicine known as Baijiang across various dimensions， including name， origin， scientific name verification， medicinal parts， production area， quality， harvesting and processing， as well as its nature， taste， and therapeutic effects， in order to provide a reference for the development and utilization of famous classical formulas containing Patriniae Herba. Patriniae Herba has a long history of use. It derives its name from the distinctive musty odor of its roots， which resembles spoiled soy sauce. However， due to its alias Kucai， there has been much confusion with other plants. Since the Ming dynasty， various plants have been used interchangeably as Baijiang. Herbal textual research showed that Patriniae Herba was first recorded in Shennong Bencaojing， and throughout history， Baijiang has been recognized as its standard name， though it has also been known by alternative names such as Luchang， Lujiang， and Suanyi. The main sources used throughout the ages were Patrinia scabiosaefolia or P. villosa， which is consistent with the 1977 edition of the Pharmacopoeia of the People's Republic of China. However， while the roots were traditionally used medicinally， the whole plant is now more commonly used in modern practice. In addition， the whole plants of Thlaspi arvense from the Cruciferae family and Sonchus brachyotus from the Compositae family are commonly used as regional substitutes for Baijiang. According to ancient records， Patriniae Herba was primarily found in Jiangxia（present-day eastern Hubei province） and Jiangdong（the region south of the lower reaches of the Yangtze River）， but modern literature shows that it is distributed throughout the country without a distinct geographical origin. In ancient times， the roots were harvested in August and sun-dried， today， the whole plant is typically dug up in summer or autumn and sun-dried. In recent times， the quality has been summarized as being best when the roots are long， the leaves are abundant and green， and the aroma is strong. Regarding the processing， ancient methods often involved baking（drying over fire）， while modern methods typically involve removing impurities， washing， and then cutting and drying the segments. The effects of Patriniae Herba are to clear heat and detoxify， eliminate blood stasis and drain pus. During the Han and Northern and Southern dynasties， it was used to treat skin diseases caused by heat， abscesses， postpartum diseases， and rheumatism， during the Five dynasties period， its therapeutic applications expanded to include diseases of the five senses， and by the modern era， conditions such as neurasthenia and insomnia were added. Regarding its properties and taste， it was recorded as bitter and neutral during the Han dynasty. By the Tang dynasty， it was slightly cold， with a taste of acrid and bitter. During the Yuan and Ming dynasties， it was mostly slightly cold and neutral， with a bitter and salty taste. In the Qing dynasty and modern times， it was mostly bitter and neutral， and in contemporary times， it has evolved to a taste of acrid， bitter， and cool. Based on the results of this study， it is recommended that when developing and utilizing famous classical formulas containing Patriniae Herba， one should select the entire herb of the historically mainstream sources， P. scabiosaefolia or P. villosa from the Valerianaceae family， and choose the processing method according to the prescription requirements. It is recommended to use raw products without specific requirements.

By consulting ancient and modern literature， this article systematically reviews and verifies the historical evolution of the herbal medicine known as Baijiang across various dimensions， including name， origin， scientific name verification， medicinal parts， production area， quality， harvesting and processing， as well as its nature， taste， and therapeutic effects， in order to provide a reference for the development and utilization of famous classical formulas containing Patriniae Herba. Patriniae Herba has a long history of use. It derives its name from the distinctive musty odor of its roots， which resembles spoiled soy sauce. However， due to its alias Kucai， there has been much confusion with other plants. Since the Ming dynasty， various plants have been used interchangeably as Baijiang. Herbal textual research showed that Patriniae Herba was first recorded in Shennong Bencaojing， and throughout history， Baijiang has been recognized as its standard name， though it has also been known by alternative names such as Luchang， Lujiang， and Suanyi. The main sources used throughout the ages were Patrinia scabiosaefolia or P. villosa， which is consistent with the 1977 edition of the Pharmacopoeia of the People's Republic of China. However， while the roots were traditionally used medicinally， the whole plant is now more commonly used in modern practice. In addition， the whole plants of Thlaspi arvense from the Cruciferae family and Sonchus brachyotus from the Compositae family are commonly used as regional substitutes for Baijiang. According to ancient records， Patriniae Herba was primarily found in Jiangxia（present-day eastern Hubei province） and Jiangdong（the region south of the lower reaches of the Yangtze River）， but modern literature shows that it is distributed throughout the country without a distinct geographical origin. In ancient times， the roots were harvested in August and sun-dried， today， the whole plant is typically dug up in summer or autumn and sun-dried. In recent times， the quality has been summarized as being best when the roots are long， the leaves are abundant and green， and the aroma is strong. Regarding the processing， ancient methods often involved baking（drying over fire）， while modern methods typically involve removing impurities， washing， and then cutting and drying the segments. The effects of Patriniae Herba are to clear heat and detoxify， eliminate blood stasis and drain pus. During the Han and Northern and Southern dynasties， it was used to treat skin diseases caused by heat， abscesses， postpartum diseases， and rheumatism， during the Five dynasties period， its therapeutic applications expanded to include diseases of the five senses， and by the modern era， conditions such as neurasthenia and insomnia were added. Regarding its properties and taste， it was recorded as bitter and neutral during the Han dynasty. By the Tang dynasty， it was slightly cold， with a taste of acrid and bitter. During the Yuan and Ming dynasties， it was mostly slightly cold and neutral， with a bitter and salty taste. In the Qing dynasty and modern times， it was mostly bitter and neutral， and in contemporary times， it has evolved to a taste of acrid， bitter， and cool. Based on the results of this study， it is recommended that when developing and utilizing famous classical formulas containing Patriniae Herba， one should select the entire herb of the historically mainstream sources， P. scabiosaefolia or P. villosa from the Valerianaceae family， and choose the processing method according to the prescription requirements. It is recommended to use raw products without specific requirements.

Objective:To investigate the effect of DExH-box helicase 9(DHX9)O-linked N-acetylglucosamine(O-GlcNAc)modifi-cation(O-GlcNAcylation)on the proliferation of hepatitis B virus(HBV)-associated hepatoma cells.Methods:The pAdTrack-TO4-DHX9-3Flag recombinant adenovirus plasmid was constructed by molecular cloning and transfected into HEK293 cells for packaging and amplification of the recombinant adenovirus AdDHX9.The interaction between DHX9 and O-GlcNAc transferase(OGT)was con-firmed using co-immunoprecipitation.The co-localization between DHX9 and OGT was measured by immunofluorescence.The level of DHX9 O-GlcNAcylation was determined using succinylated wheat germ agglutinin(sWGA)and glycosylated immunoprecipitation(IP).The effect of DHX9 O-GlcNAcylation on the proliferation of HBV-associated hepatoma cells was assessed using the colony-forming assay and cell growth curves.Results:The recombinant adenovirus AdDHX9 was successfully obtained,and DHX9 expression was confirmed by Western blot.DHX9 interacted with OGT,and the two proteins were co-localized on the nucleus.The sWGA and gly-cosylated IP experiments showed that DHX9 underwent O-GlcNAcylation,which was further enhanced by HBV infection.The colony-forming assay demonstrated that the number of cell clones was increased in the AdDHX9 group(386.667±15.630)compared with the AdGFP control group(142.667±7.572,P<0.001).Moreover,cell growth curves demonstrated that the overall cell growth rate was en-hanced in the AdDHX9 group(22.860±0.770)compared with the AdGFP control group(13.670±0.517,P<0.001).Conclusion:HBV infection promotes DHX9 O-GlcNAcylation,which enhances the proliferation of HBV-associated hepatoma cells.

Objective To investigate the effects of extracellular vesicles(EVs)derived from synovial fluid of rheumatoid arthritis(RA)patients on angiogenesis of human umbilical vein endothelial cells,and to preliminarily explore the underlying mechanisms.Methods Synovial fluid samples of knee joint were collected from 20 patients with RA and 20 patients with osteoarthritis(OA)in this study.EVs were purified using ultracentrifugation.The morphology and size of EVs were observed by transmission electron microscopy and nanoparticle tracking analysis.CD9,CD63,cytochrome c(Cyt-c),vascular endothelial growth factor(VEGF),lysyl oxidase(LOX),matrix metalloproteinase 2(MMP2),tumour necrosis factor alpha(TNF-α),transforming growth factor beta1(TGF-β1)in EVs were detected using Western blot.Human umbilical vein endothelial cells(HUVEC)were treated with the EVs.The growth,migration and angiogenesis of HUVEC were observed by CCK8 assay,TranswellTM chamber assay,scratch test and matrigel angiogenesis assay,respectively.The effect of EVs on the PI3K/AKT pathway in HUVEC was assessed using Western blot.Results Both EVs from RA synovial fluid(RA-EVs)and OA synovial fluid(OA-EVs)were cup-shaped,mainly between 30-400 nm in diameter,expressing CD63 and CD9,but not Cyt-c.RA-EVs carried more VEGF,LOX,MMP2,TNF-α and TGF-β1 than OA-EVs.Compared with the OA-EVs intervention,RA-EVs significantly promoted the proliferation,migration,and angiogenesis of HUVECs,as well as upregulated PI3K/AKT phosphorylation.The inhibitor of PI3K suppressed angiogenesis induced by EVs.Conclusion EVs in synovial fluid of RA carried more cytokines and enzymes that related angiogenesis and inflammation.These EVs exert their pro-angiogenic effects by activating the PI3K/AKT pathway,then contributing to the pathological progression of RA.

This article systematically analyzes the historical evolution of the name， origin， quality evaluation， harvesting， processing and other aspects of Picrorhizae Rhizoma by referring to the medical books， prescription books， and other documents of the past dynasties， combined with relevant modern research materials， in order to provide a basis for the development and utilization of famous classical formulas containing this medicinal herb. The research results indicate that Picrorhizae Rhizoma was first recorded in New Revised Materia Medica from the Tang dynasty. Throughout history， Huhuanglian has been used as its official name， and there are also aliases such as Gehu Luze， Jiahuanglian and Hulian. The main source of past dynasties is the the rhizomes of Picrorhiza kurrooa and P. scrophulariiflora. In ancient times， Picrorhizae Rhizoma was mainly imported by foreign traders via Guangzhou and other regions， and also produced in China， mainly in Xizang. In ancient times， it was harvested and dried in early August of the lunar calendar， while in modern times， it is mostly harvested from July to September， with the best quality being those with thick and crispy rhizomes without impurities， and bitter taste. Throughout history， Picrorhizae Rhizoma was collected， washed， sliced， and dried before being used as a raw material for medicine， it has a bitter and cold taste， mainly used to treat bone steaming， hot flashes， infantile chancre fever， and dysentery. There is no significant difference in taste and efficacy between ancient and modern times. Based on the research results， it is recommended that the rhizomes of P. scrophulariiflora in the 2020 edition of Chinese Pharmacopoeia， or the rhizomes of P. kurrooa， can be used in famous classical formulas containing this medicinal herb， which can be processed according to the processing requirements marked by the original formula. For those without clear processing requirements， the dried raw products are used as medicine.

Objective To investigate the effects of synovial fluid from patients with rheumatoid arthritis(RA)on the polarization of normal neutrophils and the MEK/ERK signaling pathway,thereby providing experimental evidence to elucidate the pathological mechanisms of RA and offering novel insights into its treatment.Methods Synovial fluid samples were collected from 20 RA patients and 20 osteoarthritis(OA)patients.ELISA was used to measure the levels of interferon-gamma(IFN-γ),tumor necrosis factor-alpha(TNF-α),transforming growth factor-beta(TGF-β)and interleukin-8(IL-8)in the synovial fluid.Neutrophils were isolated from the peripheral blood of healthy donors,and their purity was confirmed by flow cytometry.Neutrophils were then treated with synovial fluid and divided into four groups:Control(untreated),RA(treated with 10％RA synovial fluid),OA(treated with 10％OA synovial fluid),and anti-IFN-β(treated with 20 μg anti-IFN-β antibody as an N2-type control).Western blot was used to assess the changes in the expression of IFN-γ,TNF-α,TGF-β,MEK,p-MEK,ERK and p-ERK.Additionally,the MEK inhibitor PD0325901 was used to block the MEK/ERK pathway,and subsequent changes in IFN-γ and TGF-β expression in neutrophils were evaluated.Results The levels of IFN-γ,TNF-α,TGF-β and IL-8 in the synovial fluid of RA patients were significantly higher than those in OA patients.After intervention with RA synovial fluid,the relative expression of IFN-γ and TNF-α in neutrophils were significantly increased compared to those in the untreated control group and the OA group.While,TGF-β expression in the RA group was lower than that in both the control and anti-IFN-β groups.The relative expression of p-MEK and p-ERK in the RA group were significantly higher than those in the control,OA and Anti-IFN-β groups.Upon addition of the MEK inhibitor,the relative expression of p-MEK and p-ERK were reduced.Furthermore,in both the RA and OA groups,the relative expression levels of IFN-γ decreased,while the expression of TGF-β increased.Conclusion Synovial fluid from RA patients contains higher of IFN-γ,TNF-αand TGF-β,which activate neutrophils through phosphorylation of the MEK/ERK signaling pathway,promoting their polarization toward the pro-inflammatory N1 phenotype.