Bibliometric Analysis of Marine Traditional Chinese Medicine in Pharmacopoeia of the People's Republic of China: Development, Differences, and Trends Directions

Background Marine traditional Chinese medicine (MTCM) is a class of traditional medicine that has antitumor, anti-inflammatory, and antiviral properties. Bibliometric approaches were used in this study to conduct systematic research in order to gain a complete picture of MTCM research around the world. Methods CiteSpace and NoteExpress software were utilized as tools to examine the information about authors, sources, keywords, etc. Chinese publications were collected from the CNKI, VIP, and WANFANG databases; English publications were collected from the Web of Science database. Results A total of 10080 publications were screened, and the search volume of Chinese literature is greater than that of English literature; Nanjing University of Chinese Medicine, China, and Jeju National University, South Korea, published a greater number of articles than other institutions; the scholars Zhaohui-Zhang and Youjin-Jeon have published the highest number of articles in the world. MTCM of shells was often researched for inorganic elements, and data mining methods were applied frequently; MTCM of animals was commonly used for antifatigue and was taken authenticity identification owing to the scarcity of resources; scholars conducted the most research on MTCM of plants, this category usually for antitumor, anti-inflammatory, and antioxidant purposes, and the mechanisms of action were studied in depth. The Chinese literature has undertaken a multifaceted research study based on the theories of processing and the nature of TCM. In the English literature, in-depth studies have been done from the perspectives of the mechanism of action, the extraction and purification of active substances, etc. Conclusions According to the analysis of keywords, different medicinal parts present their own special research directions, and different research hotspots have also emerged under different medical theories. The development of MTCM is moving in the direction of standardization and modernization, thanks to the development of cross-disciplinary research as well as the use of several new technologies and statistical techniques.


Introduction
Te ocean accounts for more than 70% of the earth's surface area, and it is the cradle of life and a crucial source of supplies for human nutrition. Due to the particular marine environment of high salt, high pressure, hypoxia, and lack of sunlight, marine organisms and plants often produce a range of secondary metabolites with specifc activities during growth and metabolism [1][2][3]. For example, polysaccharides [4] or macrolides [5] from the ocean have, without a doubt, incalculable value in the medical area. According to the Pharmacopoeia of the People's Republic of China (ChP), marine medicines can be divided into marine traditional Chinese medicines (MTCM), marine chemical medicines, and marine biological products [6]. Among them, MTCM refers to marine natural medicines used for disease prevention and health care under the guidance of traditional Chinese medicine (TCM) theory [7,8], which include marine botanicals, marine animal medicines, and marine mineral medicines [9]. MTCM, as an important part of traditional Chinese medicine resources, is rich in resources and unique in its therapeutic benefts; its research and development have focused widespread attention on the medical profession [10][11][12]. China, as the originator of TCM, has been using MTCM to treat aliments for nearly 2,000 years, and many MTCMs have been confrmed to be medically helpful through long-term clinical trials [13]. In 2012, the "Twelfth Five-year Plan" launched in China clearly put forward the requirement of "scientifc planning for the development of marine economy, rational exploitation of marine resources, and focus on cultivation and growth of marine biomedicine." Since the implementation of this plan, MTCM has become a popular research topic in the feld of TCM. However, according to the National Oceanic and Atmospheric Administration's estimate that just 20% of the ocean has been explored by humans [14], there is still a large blank space in the human exploration of MTCM.
MTCM is rich in bioactive substances, such as terpenoids, peptides, polyethers, amino acids, lipids, fatty acids, alkaloids, saponins, organic acids, and proteins. For example, algae contain many carbohydrates and polysaccharides [15], and mineral medicine contains many inorganic salts and calcium carbonate components [16]. Tere are many organohalides and guanidine derivatives in MTCM; however, few are found in terrestrial organisms [17,18]. For instance, the tetracyclic tetraterpenoids with a novel framework were isolated from Sarcophyton tortuosum Tixier-Durivault, which is a chemical found only in the ocean [19]. Te pharmacological activity of MTCM is also broad. We had observed in our previous study that the active fucoidan (JHCF4), which is extracted from the crude fucoidan in acid-processedHizikia fusiforme, has antitumor, antioxidant, and maybe hepatoprotective properties against ethanol-induced damage [20][21][22]. Beyond that, Ostreae concha polysaccharides can boost the immune system [23]; Sargassum has efects on antitumor and antiviral therapy [24,25]; Hippocampus has a great efect on antiaging [26]; and in vitro cellular studies have also revealed that water-solubleMargaritifera concha protein has a great impact on stimulating the diferentiation of bone marrow stromal cells into osteoblasts and increasing osteoblast proliferation [27].
Bibliometric analyses were widely used to gauge the scholarly impact of scientifc publications. CiteSpace is JAVA-based virtual environment software developed with the support of Chaomei-Chen, a professor at Drexel University [28]. It was used to fnd and display new trends and developments in the scientifc literature and was also signifcantly useful software for visual analysis [29,30]. NoteExpress is a professional-grade literature search tool and management software with core functions of gathering, management, application, and mining of knowledge among other things [31]. Although more and more scholars are engaged in the study of MTCM, bibliometrics has received little attention. We chose the Chinese and English literature as the scope of the study for the frst time and applied bibliometric methodologies to conduct a systematical review of the current status and development trend of MTCM research globally from 1951 to 2020. We used the volume of articles, authors, institutions, keywords, and so on as measurement points and discussed the development, trends, directions, and diferences between Chinese and English literature. Te fndings obtained through this study will provide a more focused research perspective for subsequent scholars.

Research Methods and Related
Parameters. Node type was set to "institution, country, or keyword" based on analytical projects; time slicing was set to 5 years; pruning function was set to "pruning sliced networks"; and other parameters remained the same by default.
Te thickness of the diferent hues is related to the amount of publication, while the color of the nodes symbolizes the period. Te "colder" color indicates an earlier publication date, while the "warmer" color indicates a later publication date, and the color of the lines between the nodes refects the same meaning.
In cooccurrence and cooperative atlases, the term "centrality" refers to intermediary centrality; if centrality >0.1, the node can be regarded as a critical node; "prominence value" judges the strength of the nodes present; in the cluster atlases, "cluster ID" is the cluster's serial number, the smaller the number, the larger the cluster sizes; "size" is the number of nodes in a cluster; "silhouette" (S) is the average profle value of the clusters, while S > 0.7, the cluster is considered to be well-clustered, all nodes are similar, and the results are convincing; the clustering module's "modularity" (Q) is its value; Q > 0.3 indicates that the clustering structure is important; in a bubble chart, the size of the bubble symbolizes centrality, while diferent colors stand for diferent data sources. Figure 2 explains the meaning of the annual rings and the time represented by the color of the annual rings in diferent studies.

Analysis of Volume of Publication Published.
Because there is so much retrieved Chinese literature, the quality is spotty, with numerous "folk recipes" and "informal prescriptions." Except for analyzing the volume of literature published, other analytical project data were collected from the journal recorded in "Guide to Chinese Core Journals (GCCJ)" and the Chinese Journal of Marine Drugs.

Te Relationship between the Number of Publications and Particular
Year. After de-duplication, a total of 9,958 publications were collected, including 9,301 Chinese publications (1,559 publications from GCCJ) and 657 English publications. Figure 3 is the annual distribution trends of them. From the perspective of publication volume, the overall publication volume of Chinese literature is much higher than that of English literature, despite the fact that the number of publications in GCCJ is only marginally higher than that of English literature. From the perspective of the trend of publication volume, the publication volume of Chinese literature grew at a steady rate until the twentyfrst century. From 2000 to 2015, the number of publications rose sharply, followed by a sharp fall, whereas the number of publications in the GCCJ has remained stable since the beginning of the twenty-frst century, with no precipitous fuctuations. From 1980 to 2013, the volume of English literature progressively increased, remained steady in 2013, however, and increased dramatically in 2018, with the annual volume of literature surpassing that of the GCCJ.
As previously stated, the rapid development of the contemporary nautical and fshing industries has enabled people to better understand the sea. Due to the special growth environment of MTCM, the exploration of marine areas in China may have hit a snag since 2010. In comparison to Chinese literature, English literature is still in a phase of steady productivity, with more publications than GCCJ literature.

Number of Publications per MTCM. Information from
Chinese and English literature was unifed and summarized in NoteExpress software. We counted the amount of literature obtained for each search term separately and summarized it in WPS software before creating a double-column chart, and the results are shown in Figure 4. Te search item "Ostreae Concha" had the largest number of publications in the Chinese literature, and it was also the most regularly prescribed in MTCM prescriptions [33]. Te article "From the usefulness and utilization of Ostreae Concha to the

Cooperation Analysis of Research Countries, Authors, and
Institutions. To obtain a cooperation atlas and bubble chart, the network node was set to "country" ( Figure 5); take note that the source of the data here is from WoS. Te number of publications is the highest in China (197), followed by South Korea (115), India (69), and Japan (57), all of which have more than 50 publications. Te centrality of China reached 0.55, indicating that China is an important location for information transfer in the feld of MTCM research. We set the network node to "institution" and then fltered, merged, and renamed all institutions into frstclass institutions and visualized the data results as shown in Figure 6. Nanjing University of Chinese Medicine, China      Figure 7, Chinese scholar Zhaohui-Zhang is the author with the most publications (25) in Chinese literature and routinely collaborates on Hippocampus and Syngnathus research with Zhang et al. [35][36][37]. Changyun-Wang (22) is a professor at OUC; he conducted some research studies on the characterization and microscopic identifcation of TCM [38] as well as the activity or structure of marine fungi [39,40]. Youjin-Jeon, a South Korean scholar with the highest number of publications (30), is a professor at the College of Marine Biomedical Sciences, JEJUNU. He collaborated with Ginnae-Ahn and Fernando-Ilekuttige Priyan Shanura. [41,42]. Chao-Li, a young professor at the South China University of Technology (SCUT), is the third person to publish the most English literature. He has worked with Xiong-Fu, Qiang-Huang, and Lianghuang-Cao on a number of occasions and conducted research studies on both sea cucumbers and Sargussum [43,44]. Only Gansheng-Zhong's centrality reaches 0.1, as depicted in Figure 7(c), indicating that he was serving as a connector between authors.
To summarize, despite the fact that China is the source of MTCM with a signifcant number of publications, the collaboration network density of authors in English literature was higher than that of authors in Chinese literature. Tis fnding is consistent with the previous fndings on institutions.

Analysis of Journals.
Te top 10 lists of published journals in Chinese and English were obtained by using the "data analysis" function of NoteExpress (Tables 1 and 2). Te most published Chinese journal is the Journal of Traditional Chinese Medicine (156), which was founded in 1955. Te second place is the Chinese Journal of Marine Drugs (124), which is the frst worldwide academic journal devoted to marine medicine; however, it has a somewhat lower compound impact in comparison. Te Chinese journals studying MTCM, whose research areas focus on Chinese medicine, TCM, and pharmacology, are covered. Te English journal with the highest number of publications is Marine Drugs (95), which was established at OUC and whose founding editor-in-chief is the professor Huashi-Guan. Te overall quality of articles published in English journals is strong, and numerous highlevel journals, such as Carbohydrate Polymer Technologies and Applications, are included in JCR Q1. Te English literature consisted of approximately 200 periodicals focused on medicine, molecular biology, chemistry, fsheries, and other felds.    Figure 8 depicts the diference in the number of publications between the result of 3.1.2 and this result: the previously counted ranking list shows Ostreae Concha at the top; however, this statistic shows Haliotids Concha at the top. As a result of this fnding, we can deduce that an additional high-quality study on Haliotidis Concha has been undertaken. Tis TCM has a long history of use, and it was commonly pulverized and powdered to cure eye diseases [48]. Furthermore, it was often used to treat vertigo by Mr. Bohua-Kong, a famous old Chinese medicine practitioner [49]. Ma et al. [50] discovered that aqueous extracts of Haliotidis Concha can also decrease angiotensinconverting enzyme (ACE) activity and have a powerful and long-lasting antihypertensive impact. We can see that "data mining," "determination of inorganic elements," and "famous doctor's experience" are all prominent by observing the statistics on quantity and centrality in Figure 8(b). Due to the fact that calcium salts and microelements are the key chemical components of shellfsh class MTCM, their contents are closely associated with the efcacy and quality of MTCM, and their contents are also closely tied to the origin, growing period, and marine biological environment [51,52]. Beyond that, the combination of data mining and association rules is a novel technique to summarize and explore the medication rules of famous Chinese medicine practitioners. Figure 9 contains the keywords (category 2) cooccurrence atlas. Apart from the species nouns of Hippocampus and Syngnathus, the keyword "fatty acids" has a higher centrality than others. Both the Hippocampus and the Syngnathus contain 14 diferent types of fatty acids [53], particularly the unsaturated fatty acids ARA, EPA, and DHA, which are essential nutrients the human body cannot produce on its own [54,55]. Tey play a signifcant role in maintaining body health and curing ailments, and their contents are frequently employed as a quality evaluation index [56]. In terms of pharmaceutical efects, "antifatigue" appears in the cooccurrence atlas, and research has verifed that both the Hippocampus and the Syngnathus have antifatigue properties [57,58]. Apart from these, "morphological identifcation" and "molecule identifcation," both part of the identifcation process, indicate that scholars have conducted some discriminating research in this feld.
Te keyword analysis result for category 3 is similar to that of category 1. Scholars often apply data mining methods and regard inorganic elements as research objects. Funnily enough, the keyword "polysaccharide" appears prominently    Figure 10. Although Sepiae Endoconcha is an animal bone, it also contains substances such as mucus, polysaccharides, and enzymes [59]. Sepiae Endoconcha polysaccharide (CPS-1) has been proven in studies to speed up the healing and repair of ulcer tissue as well as have a cytoprotective efect on the stomach mucosa [60,61]. Margarita is generated in the body by stimulation of bivalves as described in Chp [62], so we classify it in the animal secretion class MTCM. By observing Figure 11, scholars generally conducted research on Chinese patent medicines containing Margarita (e.g., Liushen Pill, Zhenzhu Powder), and it was often detected by chromatography (e.g., TLC, HPLC, or GC) [63,64]. Figure 12 displays the keywords characteristics of category 5 in Chinese and English literature. Te beginning of Sargassum research in China has emphases on its active ingredients (e.g., polysaccharides, sodium alginate [65]) and their efects while combined with other TCM (e.g., Laminariae Tallus Eckloniae Tallus, Glycyrrhizae Radix Et Rhizoma [66,67]). Researchers have also looked into the extraction and pharmacological activity of polyphenolic compounds. In English literature, there is a substantial amount of research on fucoidan and seaweed polysaccharides. Te high frequency keyword count of the passages showed that most of the English literature is based on cell research in vitro and rat experiments in vivo to verify its antitumor, anti-infammatory, antioxidant, and other efects [68][69][70]. Figure 12(c) illustrated the disparities in the prominence between Chinese and English literature. Te results of keyword analysis in Chinese literature, such as "Sargassum," "Laminariae Tuallus Eckloniae Tallus," and "eighteen-clashes," show that the centrality of these words is over 0.1. Te majority of English literature keywords have a centrality of 0.03∼0.08, with the centralities of "purifcation" and "algae" being greater than or equal to 0.1. Tis result indicated that the authors of the English literature have made a thorough study of Sargassum from every viewpoint, and the researchers have spent some time thinking about the extraction and purifcation processes.

Cluster Analysis of Keywords.
Each category of keywords was administered to clustered analysis independently after being calculated by the LLR clustering algorithm, as illustrated in Figure 13, and the characteristics of each cluster are presented in Tables 3-8.

Burstiness Analysis of Countries, Authors, and
Institutions. Five burstiness atlases were collected after applying the burstiness function ( Figure 14). In Figure 14(a), Japan has the highest prominence value (14.17), followed by South Korea (6.25), but Malaysia and India were still in the emergence time range until 2020, which indicated that they were experiencing a research boom. Figures 14(b)

Leapfrog Analyses of Keywords.
Keyword leapfrog atlases were obtained by setting the presentation to "Timezone View" (Figures 15-19). Figure 15 shows that Haliotidis Concha and Margaritifera Concha appeared earlier. MTCM research on shellfsh class was limited to a single TCM from 1950 to 1980, and researchers began to explore ingredients in 1980. Te emergence of the keywords "data mining" and "association rules" around 2010 suggests that the application of various algorithms to explore medication rules became common.
Te starting point of the node leap is presented in Figure 16. After 1980, scholars conducted some research on the antifatigue efect of Hippocampus and Syngnathus

Discussion
Tis study applied CiteSpace 5.7.R2 software from the perspectives of publication number, author, institution, and keyword to research and summarize the publication situation, country-author-institution cooperation, research path evolution, and key research directions of China and other countries' research in the feld of MTCM.
Trough the analysis of the cooperation between countries, it is obvious that China was widely recognized by international peer researchers for producing high-quality and co-citated literature. South Korea, India, and Japan are all coastal countries with favorable geographic conditions and abundant natural resources. Especially in South Korea, where the aquatic industry is well developed, this condition  provides a strong technological foundation for the burgeoning businesses of marine medicine and healthy food [72]. Te cooccurrence analyses of institutions and authors showed that institutions in China and South Korea outperformed those in other countries, but the lower density of collaboration in China is a lateral expression of a lack of communication between institutions. Tis can be classifed for two reasons: frst, Chinese academics tend to conduct research from a theoretical standpoint, yet relevant records are scarce and vague, which makes research more challenging. Second, there is a big fraction of Sargassum-related topics in English literature, which is the most important reason for the high density of collaboration. To balance this situation, the Chinese government, research institutions, and scholars could consider the following perspectives.    We have three recommendations for the related departments. First of all, now that only 11 MTCM are recorded in the ChP, associated departments should strengthen the resource census and thoroughly investigate the resource base, thereby boosting more research-worthy MTCM incorporated into the ChP, such as sea cucumbers, sea urchins, and sea stars, which have established mature research systems is necessary. Secondly, through keyword cooccurrence analyses, we found the resources of some species are being depleted; for example, Hippocampus is currently in serious decline and has sufered depletion of its natural resources; it is now listed on the IUCN Red List and the China species Red List [73]. Hence, it is imperative to avoid the circulation of pseudo-mixed products in the market through morphological identifcation, molecular identifcation, and content determination. Scarce resources, such as Hippocampus and Syngnathus, should be cultured in captivity or introduced as new species, prevention of species mixing, stopping counterfeit and substandard medicines to afect the efectiveness and safety of clinical use of MTCM. Finally, establishing quality standards and clinical application guidelines through qualitative and quantitative analysis of a component of MTCM, which is common in our summarized study. We found that the quality standard of MTCM is uneven, small amount of them have an easy physical or chemical identifcation standard and few of them have a content determination, even fve diferent shellfsh MTCM but using the same calcium carbonate content determination standard [52]. Terefore, related departments should designate a development strategy for MTCM and establish a standardized technical system.
As for the advice to institutions and scholars, the following perspectives can be referred to. One of them is: Chinese scholars make up the majority of the feld, and they     are particularly interested in following up on information recorded in ancient books, which is noteworthy because there is variability between the literature and ancient books about MTCM [74]. Tis requires the scholars to apply modern information technology to delve deeply into the literature and historical materials; "data mining" and "affliate rules" present in our study ft with this phenomenon. Now, only 7 MTCM have relatively complete herbal texts [35,[74][75][76][77][78], necessitating a thorough examination of other MTCM foundation sources. Another one is: "Teory of medicinal nature" frequently appears in our cooccurrence atlases; Chinese medicinal nature is the intrinsic characteristics that distinguish TCM from other medicines [74]. We can consider that it is simpler to target key points and   improve research efciency when traditional oriental medical theory and modern western pharmaceutical theory collide. Based on the cooccurrence, clustering, and leapfrog analyses of keywords in Chinese literature, we found MTCM has specifc emphases in China, such as process methods, the medicinal nature of TCM, textual or visual identifcation of pseudo-mixes, etc. Te processing of TCM, as a unique traditional pharmaceutical technique in China, is an essential tool and an important part of ensuring the clinical efcacy of Chinese medicine [79,80]. When MTCM is processed, its medicinal efects, contents of some components, and medicinal properties may change [81][82][83]. We also concluded that scholars usually research MTCM by applying analytical tools, digging into the medication rules, and summarizing the experiences of famous doctors. After 2010, the "afliation rules" cluster emerged, which coincides with the previous statement. Afliation rule is a technique for mining valid relationships from huge amounts of valuable data. "Data mining" is an emerging discipline that combines theories and techniques from felds such as mathematics, statistics, and artifcial intelligence. Te   Evidence-Based Complementary and Alternative Medicine combination of these two has already been widely used in the TCM feld [84,85]. By classifying and analyzing the MTCM of diferent medicinal portions, we can see that mineralbased MTCM (shell, an animal's endoskeleton, and an animal's secretion) and inorganic elements and microelements were the focus of research; plant-based MTCM research in China concentrate on thyroid disorder or gall goiter, while research in other countries focuses on cancer or infammation, which is another reminder of the diferences between modern and traditional medicine and the need for integration. Animal-based MTCM employs the entire body of the animal as the source of medicine, and both have the pharmacological efect of "warming the kidney to invigorate yang" from a TCM perspective, while from a western medical point of view, they have an antifatigue efect.
Being diferent from the hotspots of research in Chinese literature, English literature focuses on Sargassum as a whole, preferring to explore the action mechanisms, extraction, and purifcation of active substances, most well studied for antioxidant and antitumor properties, but it is not limited to these two applications absolutely. Based on keywords analyses, we found that researchers often take the regulation of the signaling pathway by medicine as the starting point. Take the classical NF-κB signaling pathway as an example, infammatory stimuli activate the NF-κB inducible transcription factor, which is found ordinarily in the cytoplasm as an inactive trimer and translocated subsequently from the cytoplasm to the nucleus, increasing the development of infammation or cancer [86][87][88]. Yoon et al. [89] found that Sargachromanol G, which is isolated from the brown alga Sargassum siliquastrum, can inhibit the conversion of RAW 264.7 to osteoblasts by activating the NF-κB signaling pathway. By observing the keyword leapfrog and clustering analysis atlases, we have found that the technical combined application of chromatography, mass spectrometry, and spectroscopy is becoming increasingly common [90,91]. Combining the ability of chromatography to separate complex samples with the high sensitivity of mass spectrometry or spectroscopy to determine relative molecular mass and structural information, these facilitate the investigation of the active ingredients and structures in MTCM in more depth and optimize the extraction process [92,93].
Taken together with the discussion of keywords, it is explicit that the study of MTCM in Chinese literature started earlier while the study in English literature started later, but the pharmacodynamic mechanism is clearly defned. Currently, the main idea underlying MTCM applications in both Chinese and English literature is to screen medication lead compounds from marine resources, then developing and changing them structurally. Lastly, turn them into approapriate therapeutically medicines.
Based on the results of the analysis, a particularly large number of scholars have been studying Sargassum in recent years, in light of this, there are three proposals for subsequent scholars: frst: "sulfated polysaccharide" has a prominent place in keyword analyses and it is also verifed that appropriate sulphation changes have been proven to improve the biological activity of seaweed polysaccharides [94]. It has also been verifed that selenization leads to some changes in the monosaccharide composition, molecular weight, and surface morphology of seaweed polysaccharides, which exhibit more pronounced inhibition of α-glucosidase activity in a noncompetitive inhibition type [95]. Continuing on from this point, scientists can consider more novel ways to modify Sargassum polysaccharides, which may cause unanticipated profts. Second: the optimization of extraction process is a hot research topic in recent years; however it is well known that the extraction of seaweed polysaccharides is not high and the purifcation process needs to be optimized [96]. So, the other components of the Sargassum species, such as inorganic elements and polyphenols, are likely to play a positive role. Tird: MTCM is originated in China, although Chinese scholars and institutions are particularly engaged in this sector, the density of cooperation between institutions and authors is not excellent. As a result, cuttingedge institutions including NJUCM, CASIO, OUC, SCUT, etc. should make breakthroughs from the existing research base, strengthen communication and coordination, and collaborate closely to achieve more valuable and credible achievements.
Under the network mapping of the keyword analysis, we found the appearance of many disease symptoms refected the unique activities and potential of MTCM. More than half of the MTCM have pharmacological activities such as antioxidation, antitumor and antiviral, according to researches [97]. "Antioxidation" or "oxidative stress" can be seen everywhere in the keyword analysis atlases, which show that MTCM has a most outstanding antioxidant efect. Increased oxidative stress alters lipids, DNA, and proteins, leading to cellular infammation and programmed cell death, which play an irreplaceable role in physiopathological conditions [98]. Sargassum ilicifolium crude lipid extracts demonstrated antioxidant activity in an in vitro experiment [99]. Macroalgae are also considered to be an important source of secondary metabolites and macromolecules with antioxidant activity [100]. Cancer has become a global public health problem over the last few decades [101], and MTCM has made many inspiring achievements and formed a therapeutic system in the feld of cancer treatment [102]. Te extracts of Syngnathus have been found to inhibit tumor cell proliferation, reduce the tumor formation rate, and prolong the survival time of mice [103,104]. Fucoidan from Saccharina japonica and Undaria pinnatifda have a significant efect on antitumor activity as well [105]. Undeniably, due to the multitargeted nature of MTCM (especially compound preparations), it has been proven to be efective in treating a wide range of viral diseases [106]. Numerous components in Sargassum, including ACE inhibitory peptides and soluble dietary fbers (e.g., fucoidan, porphyran, etc.), could minimize the ACE dominance caused by SARS-CoV-2 infection, enhancing the efectiveness of the COVID-19 vaccine [107]. TCM compound preparations, which contain MTCM, have been verifed. For example, Margaritifera Concha has now been demonstrated to be efective against infuenza and herpes viruses [108]. Pharmacological efects, such as infammation [109], an anticoagulant efect [110], an antiallergic [111], an antibacterial [112], and even the treatment of obsessive-compulsive disorder [113], etc., have all been verifed.

Conclusion and Expectation
As a type of TCM with a unique growth environment, an increasing number of experts are conducting studies on MTCM, and the number of publications is growing annually. China, as a pioneer in this feld, has carried out a multifaceted, long-term study based on traditional theories (e.g., the processing theory of TCM and the theory of medicinal nature). Research points in other countries are less extensive but more in-depth (e.g., action mechanisms, extraction, and purifcation of active substances) than research points in China. Meanwhile, the modernization of Chinese research has been aided by scientifc thoughts from other countries. By separating the analysis of MTCM according to diferent medicinal parts, we also found differences in research hotspots between them. Interdisciplinary research can help maximize the benefts of MTCM in the battle against diseases such as cancer, oxidative stress, infammation, and viral infection. According to recent research hotspots and trends, the return of ancient TCM books, the updating of analytical techniques and tools, the organic integration of the "holistic concept" of traditional medicine and the "individual concept" of modern medicine, the exploration and modifcation of active ingredients, and the in-depth study of marine organisms (e.g., algae) are all top priorities for all scholars.
Te vast majority of MTCM uses plants and animals grown in the ocean as a source of medicine. MTCM as a medicine source is the main difculty and obstacle to the development of marine medicine, but it can also be the greatest advantage and the strongest foundation for marine medicine [114]. At this stage, accelerating the development and industrialization of marine Chinese medicine is a major problem. From the emergence of Chinese frst marine drug (Poly Saccharide Sulphate, PSS ® ), which was extracted from natural Sargassum in 1985 [115], to the proposal of the "Blue Drug Store" development plan in 2016, all these inspiring results showed that MTCM, which originated in China, is merged with modern concepts and embodies a wealth of values. It is undoubtable that "blue pharmaceutical" will become a leading high-tech industry as a result of further indepth research and development in the feld of marine medicine.

Conflicts of Interest
Te authors declare that they have no conficts of interest.