Standardization is the universal language of the world, and standardization of traditional Chinese medicine (TCM) is essential for its communication in China and globally. However, the principles and methods of TCM acupuncture standardization have been unclear and inadequate in the early stages. Based on an investigative approach to understanding the current status, identifying problems, and finding solutions, our team has established basic principles of TCM acupuncture that embody Chinese wisdom, evaluated the international strategic environment systematically, proposed the principle of “importance of harmony and exercise of impartiality”, and established basic working principles. A series of methods for TCM acupuncture standard development and evaluation have been constructed, including general standards for the revision of TCM acupuncture standards, the first TCM acupuncture clinical research management specification, a shared full chain technology platform, a data center, and an evaluation research base for TCM acupuncture clinical research. Evaluation criteria for ancient literature and expert experience, a recommendation method for the “three main and three auxiliaries” TCM guideline for prevention were established, and quantifiable assessment methods of TCM standard applicability were proposed. These findings provide methodological guidance for TCM acupuncture standardization.

【Objective】 To provide a new idea for the treatment of depression by summarizing the antidepressant effect and mechanism of active ingredients in functional food, and medicine and food homologous products. 【Methods】 The literature related to the antidepressant of functional food or medicine and food homologous products from September 25, 1996 to September 5, 2022 was collected through PubMed, Google Academic, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. After that, their antidepressant active ingredients and mechanism of action were systematically summarized and analyzed. 【Results】 A total of 146 pieces of literature were involved in the study, including 67 plant-derived functional foods or medicine and food homologous products, 32 antidepressant extracts (including 8 flavonoid extracts), and 87 antidepressant active ingredients. The 87 antidepressant active ingredients include 7 terpenes, 22 saponins, 15 flavonoids, 11 phenylpropanoids, 7 phenols, 6 sugars, 8 alkaloids, and 11 others. 【Conclusion】 The study summarized and analyzed the active ingredients and mechanisms of antidepressants in functional foods and medicine and food homologous products, which provides a new vision for the development of new antidepressants and a potential alternative treatment for patients with depression.

【Objective】 This study aims to summarize the hotspots of acupuncture research in China and abroad in recent 10 years. 【Methods】 The core collection of Web of Science was retrieved, and the literature on experimental and clinical research of acupuncture in China and abroad was collected from January 1, 2012 to December 31, 2021. The included literature was visually analyzed using CiteSpace 6.1.R3. Statistical analysis was carried out in the annual number of papers, authors, countries, and journals. According to the author's country, the literature was divided into Chinese and global categories for keywords clustering analysis and co-citation references analysis independently to obtain hotspots and trends in acupuncture research. 【Results】 There are 1 215 articles in acupuncture experimental medicine, 3 805 articles in acupuncture clinical medicine in China; 551 articles in acupuncture experimental medicine, and 4 538 articles in acupuncture clinical medicine abroad. The number of articles on acupuncture abroad remains stable and flat, whereas the annual number of domestic papers shows a continuously growth trend. LIU Cunzhi from Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University in China is the author who has published the most articles in the field of acupuncture in the recent decade. China is the most productive country in publishing such research articles. Evidence-based Comprehensive and Alternative Medicine is the journal with the most published articles. The mechanisms of acupuncture on nerve regeneration or nerve recovery and research on the mechanisms of acupuncture analgesia are hotspots in experimental acupuncture research, and the treatment of neuropathic pain and dysfunctional diseases with acupuncture are hotspots in clinical acupuncture research in China. Research on the mechanism of protection of the cardiovascular system by acupuncture and research on the mechanism of analgesia by acupuncture are hotspots in experimental research on acupuncture abroad. Studies on the amelioration of inflammatory pain and psychological or psychiatric disorders by acupuncture also serve as hotspots in clinical research on acupuncture abroad. 【Conclusion】 Acupuncture research in China focuses on the treatment of internal diseases and visceral pain, while acupuncture research abroad concentrates on the alleviation and improvement of cancer and psychological and mental diseases. Treatment of internal diseases and mental diseases with acupuncture is the trend of future research.

【Objective】 To explore the current status and development trend of research on external therapies in traditional Chinese medicine (TCM) for insomnia over the past 10 years through bibliometrics and visual analysis, to provide references for further research on the topic. 【Methods】 Literature relating to TCM external therapies for insomnia from January 1, 2012 to December 31, 2021 was retrieved from Chinese databases, including China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and from the Web of Science Core Collection (WOSCC) for English articles. CiteSpace, VOSviewer, Scimago Graphica, and NoteExpress software were used to analyze publication volumes of the papers and how they were distributed in different journals, as well as to visualize the data of the countries, authors, institutions, and keywords. 【Results】 A total of 6 085 papers were obtained, of which 5 592 were from the Chinese databases and 493 were from the English database, with their publication volumes growing steadily year on year. Approximately 45 countries and regions were found to have published research on the topic. In terms of Chinese publications, the author with the most papers published was CHEN Yunfei from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine. The closest collaboration was between LIU Chengyong from the Affiliated Hospital of Nanjing University of Chinese Medicine and YUE Zenghui from Hunan University of Chinese Medicine. In terms of English publications, the author with the most papers published was MAO Junj from Sloan-Kettering Cancer Research Center, USA, and LAO Lixing from the University of Hong Kong was his closest partner in collaboration. Heilongjiang University of Chinese Medicine was the institution with the most Chinese publications, and Shanghai University of Traditional Chinese Medicine was the one with the most English papers published. Studies on the topic were published in 386 Chinese journals and 205 English journals, respectively. Nowadays, the clinical application of TCM external treatments for insomnia, the selection of meridians and acupoints, therapies for insomnia and its related diseases are research hotspots. The combined use of different TCM external therapies is a trend in the treatment of insomnia and its concomitant diseases, especially in the fields of oncology, nursing, and psychiatric disorders. The exploration of mechanisms of TCM external therapies for insomnia is also a key direction for future research. In clinical practice, the commonly used external therapies for insomnia include acupuncture, ear-acupressure with beans, acupoint application, etc. The commonly selected acupoints are auricular points, Sishencong (EX-HN1), Shenmen (HT7), etc. The frequently studied meridians are Ren, Du, Qiao, etc. The insomnia concomitant diseases are depression, stroke, anxiety, etc. 【Conclusion】 A wealth of research results have been accumulated in the treatment of insomnia by TCM external therapies, but authoritative research results are not so many. Therefore, institutions in different countries should strengthen communications and cooperation, and researchers should be encouraged to make innovations and breakthroughs on the basis of inherited TCM external therapies, so as to produce more valuable research results and improve TCM external therapies for providing better treatments for patients with sleep disorders.

【Objective】 To dig the main active components and predict potential mechanisms of Guarana in the treatment of Alzheimer’s disease (AD) by network pharmacology method and molecular docking. 【Methods】 By digging into papers relating to this topic, chemical components in Guarana were obtained and used for drug-likeness analysis. Databases including HERB and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were used to obtain potential targets that the active components in Guarana might have effects on, and to find out diseases in association with the potential targets. Other databases such as GeneCards, a human gene database, and DisGeNET were used to identify the genes relating to AD, and a Wayne diagram was drawn to get the intersected targets in Guarana and AD. Subsequently, CytoScape software was adopted for the construction of a Guarana-intersected targets-AD map. After that, the intersected targets were uploaded to the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to acquire a protein-protein interaction (PPI) network diagram. Then, the key target proteins were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). In terms of molecular docking verification, AutoDock software was used to verify whether the crucial active compounds of Guarana’s components could bind to the key targets. 【Results】 A total of 140 potential targets for Guarana to treat AD were obtained. The results of PPI network analysis showed that interleukin 6 (IL-6), tumor necrosis factor (TNF), insulin (INS), mitogen-activated protein kinase 3 (MAPK3), transcription factor (JUN), cell tumor antigen p53 (TP53), caspase3 (CASP3), protein c-Fos (FOS), catalase (CAT), and Catenin beta-1 (CTNNB1) might be the key targets of Guarana in the treatment of AD. It was found by GO and KEGG analyses that the mechanism of Guarana in the treatment of AD might be the bindings between Guarana compounds and protease outside the cell membranes. The molecular docking results showed that the small molecules of various components in Guarana binding to target proteins such as TNF, IL-6, MAPK3, and FOS needed relatively less energy. 【Conclusion】 The treatment of AD with Guarana involves the participation of multiple targets, among which IL-6, TNF, and MAPK3 might be the key ones. These key targets might take effects through the biological process in their bindings to β-amyloid and involving signaling pathways in cancer. Hopefully, our research could offer some scientific foundations as well as references for in-depth studies on the treatment of AD with Guarana.

【Objective】 Loxosceles spider bite accidents are rising in wide areas of the world which necessitates the exploration of natural inhibitors to inhibit the most significant enzymes, namely sphingomyelinase D (Smase D) and hyaluronidase. 【Methods】 Virtual screening using traditional Chinese medicine (TCM) against Smase D (PDB ID: 2F9R) and hyaluronidase was performed by the DrugRep server. Absorption, distribution, metabolism, and excretion (ADME) parameters were predicted via the same server. In addition, molecular dynamics (MD) simulation was conducted using CABS-flex 2.0 tool to prioritize the best potential natural inhibitors. 【Results】 Tiliroside and Digitoxin were the best natural inhibitors from TCM to Smase D and hyaluronidase in terms of molecular docking and ADME parameters, while Digitoxin and β-carotene were the most potent inhibitors against hyaluronidase. MD simulations demonstrated the stability of the docked complexes. 【Conclusion】 In-silico inhibition of Loxosceles spidervenom enzymes through TCM was demonstrated, which deserves wet-lab experimentation.

【Objective】 To reveal the integral in vivo polypharmacokinetics (PPK) similarity or difference between Jinyinhua (Lonicerae Japonicae Flos, LJF) and Shanyinhua (Lonicerae Flos, LF), and provide reference for their clinical application. 【Methods】 The PPK model and its total quantum statistical moment similarity (TQSMS) method were used to compare the integral PPK profiles of nine components with anti-inflammatory efficacy (rutin, caffeic acid, chlorogenic acid, cryptochlorogenic acid, dispsacoside B, macranthoidin B, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C) of LJF and LF. A total of 54 Specific Pathogen Free (SPF) grade Kunming (KM) mice were randomized into LJF group and LF group (n = 27), and each group was divided into nine subgroups (n = 3) according to different time points. Subsequently, mice model of p-xylene-induced ear edema was constructed by oral administration of LJF and LF. The concentrations of the nine anti-inflammatory components in plasma samples of the mice were determined by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). And the pharmacokinetics (PK) parameters of single component and the integral PPK parameters [total quantum statistical moment (TQSM) and TQSMS] of multiple components were calculated by Drug And Statistics (DAS) software and home-brew programs with Excel, respectively. 【Results】 There were significant differences in single-component PK parameters between LJF and LF (P < 0.05). Whereas, no significant differences were found in multi-component TQSM parameters, including total quantum zero moment (AUCT0-t, AUCT0-∞) and total quantum first moment (MRTT0-t, MRTT0-∞) for the total quanta (P > 0.05). Accordingly, single-component TQSMS varied from 0.220 4 to 0.968 9, and that for the total quanta was 0.828 4, suggesting no significant differences in the speed and extent of bioavailability between LJF and LF. Furthermore, in light of high TQSMS (0.828 4), the integral PPK profiles of the nine anti-inflammatory components of LJF and LF were similar under 90% confidence intervals. 【Conclusion】 The PPK model and its TQSMS method are appropriate and efficient to compare the similarity or difference of integral PPK profiles of multi-component herbal medicines. It is suggested in this research that LJF can be replaced with LF or vice versa for anti-inflammatory treatment.

【Objective】 To investigate the mechanism of Yishen Tonglong Decoction (益肾通癃汤, YSTLD) inhibiting the toll-like receptor 4/p38 mitogen activated protein kinases/nuclear factor kappa-B (TLR4/p38 MAPK/NF-κB) signaling pathway against prostate cancer by up-regulating miR-145-5p. 【Methods】 miRNA microarray technology was used to detect the changes of miRNA expression profile in prostate cancer PC-3 cells treated with YSTLD, and miRNAs with marked differences in miRNA microarray results were screened and validated by real-time polymerase chain reaction (qRT-PCR). Lentiviral transfection of miR-145-5p into prostate cancer PC-3 cells, Cell Counting Kit-8 (CCK8) assay, and scratch assay were adopted to detect the effects of miR-145-5p on prostate cancer PC-3 cell proliferation and migration. qRT-PCR and Western blot were employed to detect the effects of miR-145-5p on TLR4/p38 MAPK/NF-κB signaling pathway and the expression levels of apoptosis-related genes caspase3, tumor necrosis factor-α (TNF-α), Bax, and Bcl-2. qRT-PCR and Western blot were used to detect the effects of serum containing YSTLD on miR-145-5p, TLR4/p38 MAPK/NF-κB signaling pathway, and the expression levels of apoptosis-related genes caspase3, TNF-α, Bax, and Bcl-2. 【Results】 The expression levels of 35 miRNAs in prostate cancer PC-3 cells treated with YSTLD were significantly different from those in the control group, with miR-145-5p being the most significantly different; qRT-PCR validation revealed that the miR-145-5p levels in prostate cancer PC-3 cells treated with YSTLD were significantly higher than those in the DMSO control group (P < 0.05). After lentiviral transfection of miR-145-5p into prostate cancer PC-3 cells, miR-145-5p was found to inhibit the proliferation and migration of prostate cancer PC-3 cells. Overexpression of miR-145-5p up-regulated expression levels of caspase3, TNF-α, and Bax mRNA, and down-regulated expression levels of p38 MAPK, p65 NF-κB, and Bcl-2 mRNA in prostate cancer PC-3 cells (P < 0.05), while up-regulated caspase3 protein expression levels in prostate cancer PC-3 cells and down-regulated expression levels of TLR4, p38 MAPK, and p65 NF-κB protein (P < 0.05). Serum containing YSTLD could up-regulate the expression levels of caspase3, TNF-α, and Bax mRNA, and down-regulate the mRNA expression levels of p38 MAPK, p65 NF-κB, Bcl-2, and TNF receptor-associated factor 1 (TRAF1) in prostate cancer PC-3 cells after intervening prostate cancer PC-3 cells (P < 0.05). Simultaneously, it up-regulated the expression levels of caspase3 protein and down-regulated the protein expression levels of TLR4, p38 MARK, p65 NF-κB, and TRAF1 in prostate cancer PC-3 cells (P < 0.05). 【Conclusion】 YSTLD can promote apoptosis of prostate cancer PC-3 cells by up-regulating the expression level of miR-145-5p and inhibiting TLR4/p38 MAPK/NF-κB signaling pathway, which may be an important mechanism of YSTLD against prostate cancer.

The successful retrieval of ancient mitochondrial DNA (mtDNA) from Neanderthals provides powerful experimental evidence that clarifies the arguments between the out-of-Africa and multiregional models of evolution. However, the lack of nuclear DNA from Neanderthal fossils and mtDNA of early modern human fossils dating back to approximately the same time in the Pleistocene constitutes a limitation that may compromise the significance of mtDNA phylogenetic analysis. In this report, we introduce a mitochromic analysis using Neanderthal mtDNA as a foreign transgene and humans as a naturally occurring transgenic species. Forty Neanderthal mtDNA retrievable nuclear fragments were identified by blasting human genome data with Neanderthal mtDNA. Five of the 40 fragments exhibited higher correlation with Neanderthal mtDNA than those with modern human mtDNA. Furthermore, these five nuclear fragments harbor Neanderthal mtDNA-unique haplotypes. Based on the 98%+ identity between Neanderthal and modern human mtDNA when compared by groups, we suggest that some of the modern human nuclear fragments retrieved using Neanderthal mtDNA may aid in decoding Neanderthal genetic information, and also may simultaneously demonstrate a close genetic evolutionary relationship between modern humans and Neanderthals.

Objective This study focused on the application regularity of medicinal and dietary substances (MDS) of traditional Chinese medicine (TCM) diet therapy during rehabilitation, in order to help patients with Corona Virus Disease 2019 (COVID-19) reduce sequelae and improve their life quality. Methods The official websites of the national and provincial health committees, the website of the National Administration of Traditional Chinese Medicine, the China BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database were used to search the keywords, such as “coronavirus” “novel coronavirus pneumonia” “COVID-19” “protocol” “guideline” “consensus” and “rehabilitation period”. The search time was from the establishment of databases to July 31, 2022. The prevention and control protocols of various provinces and cities were manually supplemented and screened out. The information on the frequency, property, flavor, meridian tropism, and efficacy of MDS was collected for association rule analysis through the Apriori algorithm. Hierarchical cluster analysis was performed using the Euclidean distance and longest distance. Results A total of 18 protocols were screened out, including 56 lists of TCM diet therapy, and 47 kinds of MDS with a frequency of 132 times during the rehabilitation of COVID-19. Among them, six lists of diet therapy were collected from national websites, 26 from local government websites, and 24 from social and academic institution websites. The intended population can be divided into seven categories including normal recovery, lung-spleen Qi deficiency, deficiency of both Qi and Yin, spleen-stomach weakness, deficiency of Yang Qi, kidney Qi deficiency, and blood deficiency. Shanyao (Dioscoreae Rhizoma) and Lianzi (Nelumbinis Semen), followed by Dazao (Jujubae Fructus) were used most commonly in MDS, with mainly flat property, sweet flavor, and spleen and lung meridians in meridian tropism. Besides, deficiency-tonifying drugs were commonly used in MDS. Through association rule analysis, 12 groups of association MDS pairs were obtained. The pair of Yiyiren (Coicis Semen) and Chenpi (Citri Reticulatae Pericarpium) had the highest Lift value, and Yiyiren (Coicis Semen) was used most frequently in the MDS category for eliminating pathogenic factors. The results of complex network analysis showed that the core MDS were Yiyiren (Coicis Semen), Shanyao (Dioscoreae Rhizoma), Huangqi (Astragali Radix), Fuling (Poria), and Dazao (Jujubae Fructus). Three core categories were classified by cluster analysis, including the category of strengthening spleen, nourishing kidney, and grasping Qi, the category of removing phlegm, abating panting, and regulating Qi, and the category of strengthening the middle-energizer and reinforcing Qi. Conclusion Based on the TCM theory, most patients during the rehabilitation of COVID-19 are in a state of lingering pathogens due to deficient vital Qi. TCM diet therapy is based on the principle of “giving both reinforcing and reducing treatment”, and the MDS combinations focus on both reinforcing the health Qi and eliminating pathogenic factors. The diet therapy mainly uses the MDS with flat property and sweet flavor, which belongs to deficiency-tonifying drugs, adding suitable MDS of pathogen-eliminating drugs according to different situations. The ultimate goal is to promote lung inflammation absorption, improve pulmonary fibrosis, increase immunity, reduce the occurrence of sequelae, and improve life quality.