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.

ObjectiveBased on traditional quality evaluation of Gardeniae Fructus（GF） recorded in historical materia medica， this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics， microscopic features， and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length， diameter and individual fruit weight of wild and cultivated GF， and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF， and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently， the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China， the starch content was measured by anthrone colorimetric method， the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method， the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection（HPLC-ELSD）， and the contents of representative components in them were measured by ultra-performance liquid chromatography（UPLC）. Finally， correlation analysis was conducted between quality traits and phenotypic traits， combined with multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， key differential components between wild and cultivated GF were screened. ResultsIn terms of traits， the wild GF fruits were smaller， exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger， displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF， while the blue-yellow value（b^*） of wild GF was significantly higher than that of cultivated GF. In the microstructure， the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals， while the endocarp contained stone cell class round， polygonal or tangential prolongation， undeveloped seeds were visible within the fruit. In contrast， the mesocarp of cultivated GF contained few calcium oxalate cluster crystals， or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like， with the innermost layer arranged in a grid pattern. Seeds were basically mature， and only a few immature seeds existed in some batches. Regarding primary metabolite content， wild GF exhibited significantly higher total polysaccharide level than cultivated GF（P<0.01）. In category-specific component content， wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF（P<0.01）. Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside， deacetyl asperulosidic acid methyl ester， gardenoside and chlorogenic acid compared to cultivated GF（P<0.01）. Conversely， the contents of genipin 1-gentiobioside， geniposide and genipin were significantly lower in wild GF（P<0.01）. ConclusionThere are significant differences between wild and cultivated GF in terms of traits， microstructure， and contents of primary and secondary metabolites. At present， the quality evaluation system of cultivated GF remains incomplete， and this study provides a reference for guiding the production of high-quality GF medicinal materials.

This article systematically reviews and verifies the name， origin， production area， quality evaluation， harvesting， processing and other aspects of Cynanchi Atrati Radix et Rhizoma（CARR） by consulting relevant ancient and modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. Through textual research， Baiwei has been the official name for CARR， though it also bears alternative names such as Chuncao， Popo Zhenxianbao， Longdan Baiwei. The mainstream base is the roots and rhizomes of Cynanchum atratum. Historical records indicate primary producing areas include Shandong， Anhui， Jiangsu， Shaanxi and Shanxi. Since the late Ming dynasty， varieties from Juxian， Yishui and Rizhao in Shandong have been highly regarded as authentic， commonly known as eastern Baiwei. Since modern times， its quality has been summarized as fine， slender， and straight fibrous roots， pale yellow exterior， whiter interior， and dryness with easy breakability are considered superior. The harvesting time before the Song dynasty was on the third day of the third lunar month， but after the Song dynasty， harvesting was possible in both spring and autumn. The initial processing methods of CARR in ancient times included drying in the shade， removing Lu（the little rhizomes which are on tap of roots）， and removing mustaches， modern methods involve washing and sun-drying. During the Northern and Southern dynasties， processing methods included steaming. In the Song dynasty， drying and light stir-frying were predominant， while wine washing emerged in the Ming dynasty. Modern practices primarily involve using raw， stir-frying or honey processing. Regarding the medicinal properties of CARR， both ancient and modern texts agree it has a bitter and salty taste and is non-toxic. Records prior to the Qing dynasty predominantly describe its nature as extremely cold， while mainstream herbal texts after the Qing dynasty generally characterize it as cold. Before the Ming dynasty， there were no records of its meridian tropism. It was not until the Qing dynasty that it was recorded in the lung meridian. Modern records mainly refer to the stomach， liver， and kidney meridians. Throughout history， its main functions have been to clear heat， diuresis， nourish Yin， and replenish essence， primarily treating Yin deficiency and fever syndrome. Based on the research results， it is suggested that when developing famous classical formulas containing CARR， the dried roots and rhizomes of C. atratum can be selected as its medicinal source. If there are no specific processing requirements， raw products can be selected as medicine. If the processing requirements are specified， corresponding processed products can be selected as medicine according to the original formula requirements.

ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

This article systematically reviews and verifies the medicinal materials of Dioscoreae Hypoglaucae Rhizoma（DHR）， Dioscoreae Spongiosae Rhizoma（DSR）， Smilacis Chinae Rhizoma（SCR） and Smilacis Glabrae Rhizoma（SGR） from the aspects of name， origin， producing area， quality， harvesting， processing and efficacy by consulting historical literature， in order to provide reference for the development and utilization of famous classical formulas containing the four medicinal materials. DHR， DSR， SCR and SGR have a long history of application as medicinal materials. However， due to their similar growth environment and medicinal properties， as well as their functions of promoting dampness， dispelling wind and removing numbness， there have been instances of homonymous foreign objects and homonymous synonyms throughout history， resulting in confusion of the origin. Therefore， it is necessary to conduct comparative analysis and systematic research for clarifying the historical development and changes of the four， in order to provide a basis for safe and effective medication. According to research， Bixie was first recorded in Shennong Bencaojing and has been historically known as Baizhi， Chijie， Zhumu， and other aliases. From ancient times to the mid-20th century， there has always been a situation where the rhizomes of Dioscorea plants and Smilax plants， and even the rhizomes of Heterosmilax plants， were mixed together to be used as medicinal herbs for Bixie. However， since the Tang dynasty， it has been clearly advocated that the rhizomes of Dioscorea plants have excellent quality and have been the mainstream throughout history. The 2020 edition of Chinese Pharmacopoeia categorized it into two types of medicinal herbs（DHR and DSR）. Among them， the origin of DHR is the dry rhizomes of Dioscorea hypoglauca， and the origins of DSR are the dry rhizomes of D. spongiosa and D. futschauensis. In ancient times， due to different types， the corresponding production areas of DHR and DSR were also different. Nowadays， They are mainly produced in the southern region of the Yangtze River. Since the Tang dynasty， the quality of Bixie has been characterized by its white color and soft nature. In modern times， it has been summarized that those with white color， large and thin pieces， powdery texture， tough and elastic texture， and neat and unbreakable are the best. The harvesting times of DHR and DSR are in spring or autumn， with the best quality harvested in autumn. The mainstream processing methods of them are slicing and then using the raw products or wine-processed products. SCR was first recorded in Mingyi Bielu and has been known as Jinganggen， Tielingjiao， Tieshuazi， and other aliases in history. The mainstream source is the dry rhizomes of Smilax china in the past dynasties， with the best quality being those that are tough and rich in powder. The harvesting time is from the late autumn to the following spring， and the main processing method throughout history has been slicing for raw use. SGR was first recorded under the item of Yuyuliang in Variorum of Shennong's Classic of Materia Medica. It was listed as an independent medicinal material from Bencao Gangmu. In history， there were such aliases as Cao Yuyuliang， Lengfantuan， Xianyiliang， Tubixie， etc. The main source of the past dynasties was dry rhizomes of S. glabra. In history， there have also been instances of multiple plants belonging to the same genus， and even cases of mixing the rhizomes of plants in the genus Heterosmilax. It is mainly produced in Guangdong， Hunan， Hubei， Zhejiang， Sichuan， Anhui and other regions， its quality has been summarized as large in size， powdery in texture， with few veins， and light brown in cross-section since modern times. The harvesting time is in spring or autumn， and the main processing method throughout history has been slicing for raw use. DHR， DSR， SCR and SGR all have the effects of promoting dampness， dispelling wind， relieving rheumatism and detoxifying. However， their detoxification abilities are ranked as follows：SGR>SCR>Bixie（DHR and DSR）. Especially for the treatment of limb spasms， arthralgia and myalgia， scrofula， and scabies caused by syphilis and mercury poisoning， SGR has a unique effect. Based on the research results， DHR is recommended to develop the famous classical formulas containing Bixie as the first choice for medicinal herbs. It should be harvested in autumn， sliced thinly while fresh， and processed according to the requirements of the famous classical formulas， without any requirements for raw use. Selecting the rhizomes of S. china， harvested in late autumn， and thinly sliced while fresh. If there are no special processing requirements in the formulas， use it raw. Selecting the rhizomes of S. glabra， it is harvested in autumn and thinly sliced while fresh. If there are no special processing requirements in the formulas， raw products can be used.