Objective: Lingzhihuang capsule (LZHC) is a natural product that consists of 10 commonly used medicinal plants, and it is used in traditional Chinese medicine to promote people's overall health. Previously, LZHC was successfully used as adjuvant therapy for treating patients with cancer. However, the chemical constituents of LZHC and their potential biological functions remain unclear. The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods: The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry combined with mass spectrometry-based molecular networking. The targets were predicted using SwissTargetPrediction software, and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results: We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking, including triterpene (the main structural type) and other clusters (ie, flavonoids and organic acids). Our results suggested that multiple pivotal targets were regulated by LZHC, including tumor necrosis factor, nitric oxide synthase 2, glucocorticoid receptor, estrogen receptor, 3-oxo-5-alpha-steroid 4-dehydrogenase 2, prostaglandin e2 receptor ep4 subtype, estrogen receptor beta, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, mitogen-activated protein kinase 3, and rac-alpha serine, which are related to signal transduction, positive regulation of transcription from RNA polymerase II promoters, oxidation-reduction processes, inflammatory responses, and other biological processes. Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC, such as cancer-related proteoglycans, the PI3K-Akt-signaling pathway, and the cAMP-signaling pathway.Conclusions: Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation, anti-aging, and tumor suppression.

Acupuncture originated in China and is an important component of traditional Chinese medicine. The elucidation of its anesthetic mechanisms, the medical needs of Western societies, as well as the proven therapeutic effects of this technique have made it the most widely used medical practice in the world. The concept of evidence-based medicine has been introduced in acupuncture research for technical improvement and the production of high-quality clinical evidence. Upon reviewing the acupuncture clinical research over the past 10 years, we found the gradually increasing range of diseases that it benefits, from pain management to neoplasms and genitourinary, digestive, and mental disorders. Acupuncture is included in a number of international guidelines for clinical practice. However, high-quality clinical evidence to support the efficacy and effectiveness of acupuncture is lacking as a result of multiple exceptional clinical trials conducted by Western researchers that have yielded antagonistic results. Future clinical research should focus on exploring objective evaluation methods for studying the therapeutic effects of acupuncture.

Objective: Polygonum multiflorum Thunb. (PMT) is a widely used traditional Chinese herbal medicine with a variety of pharmacological effects. This study investigates the chemical composition of a water extract of PMT and its potential as a therapy for osteoarthritis (OA).
Methods: The components of the aqueous extract of PMT were determined using high-performance liquid chromatography (HPLC). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of a gene expression dataset downloaded from the Gene Expression Omnibus (GEO) were performed using Limma in R language. Differential chondrocyte metabolites were determined using gas chromatography-mass spectrometry (GC-MS) before and after treatment.
Results: The water extract of PMT showed good ability in improving OA, and the content of the active ingredient emodin increased significantly after processing. Analysis of the GEO database further demonstrated a strong association between OA and metabolic pathways. Emodin promotes chondrocyte proliferation and significantly reduces the number of inflammatory factors. The metabolomic results showed that emodin affected five metabolic pathways related mainly to primary bile acid biosynthesis, steroid biosynthesis, and biosynthesis of unsaturated fatty acids.
Conclusions: This study revealed the pharmacological effects of PMT and emodin as the main active components, thereby providing a scientific basis for the treatment of OA.

Gout is a common of inflammatory arthritis and is caused by the deposition of monosodium urate (MSU) crystals as a result of hyperuricemia (HUA). Although HUA is considered to be the main risk factor for gout, only approximately 10% of the individuals with HUA will eventually experience a gout attack. In this review, we first briefly introduce the development of gout and then summarize several possible reasons for its development. Genetic factors play a more prominent role in gout than in other diseases; functional mutations related to urate control and innate immunity components have been found to be associated with gout. Here, we list some of the most prominent genes involved in the pathogenesis of gout. In joints with MSU deposition, mature macrophages may uptake MSU crystals without causing inflammation, and this helps to maintain joints in an asymptomatic state. As an auxiliary inflammation pathway, the ATP-P2X7R-NLRP3 axis may contribute to the amplification of MSU-induced inflammation to affect the development of gout. Finally, this review summarizes the research progress on natural products that can be used in the treatment of HUA and gout.

Objective: This study aimed to explore the effects of Chinese patent medicine (CPM) in reducing the incidence of major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD) angina pectoris and improving clinical effectiveness and provide evidence for its use as clinical adjuvant therapy.
Methods: Twenty-eight thousand five hundred and seventeen patients hospitalized with CHD angina pectoris from 6 hospitals were divided into CPM group (n = 11,374) and non-CPM group (n = 17,143) to evaluate the incidence of MACE, including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting.
Results: The incidence of MACE in the CPM group was lower than that in the non-CPM group. CPM therapy was an independent protective factor that reduced the overall risk of MACE [adjusted hazard ratio = 0.40, 95% confidence interval (0.33; 0.49)]. Patients in the CPM group who received one, two, or three types of CPM could benefit from adjuvant treatment with CPM, and taking more types of CPM was associated with a lower risk of MACE. In addition, the male population was better than the female population in taking CPM, and middle-aged people aged 55 to 64 were more suited to take CPM based on Western medicine.
Conclusions: The use of CPM as adjuvant therapy can decrease the occurrence of MACE in patients with CHD angina pectoris, especially in men and middle-aged people, and the drug treatment plan should be optimized accordingly. However, this conclusion needs further verification by prospective cohort studies in the future.

Recently, traditional Chinese medicine-based treatment has succeeded in fighting coronavirus disease 2019 (COVID-19), and Rhizoma polygonati (Huangjing) has been one of the recommended components. Its processed products play antidiabetic, antiviral, antitumor, antioxidation, antifatigue, antiaging, and immune enhancement roles. The climate in Mount Tai is mild, and the dense forest is suitable for the growth of Rhizome polygonati, which has gradually evolved into a unique specie. Considering the important medicinal value and pleasant taste of Mount Tai-Rhizoma polygonati, various healthy and functional food products, controlled by quality markers with anti-COVID-19 potential, as well as emergency foods can be developed. The study aimed to review current evidence on the nutritional value of Rhizoma polygonati from Mount Tai and its usefulness as a traditional Chinese medicine, source of herbzyme, and potential remediating agent for COVID-19 and food shortage. Most recent findings regarding herbal nanomedicine have revealed that nanoscale chemical compounds are potentially efficient in drug delivery or nanozyme catalysis upon bioprocessing. Nanoflower structure is found in processed Rhizoma polygonati by self-assembly and has wide application in enzymatic events, particularly nanoscale herbzyme. The novel findings regarding Mount Tai-Rhizoma polygonati could enhance its novel applications in chronic and hidden hunger, clinical nanomedicine, and as an anti-COVID-19 agent.

Acupuncture dose-effect relationship is the essential feature of acupuncture and the key factor of acupuncture's therapeutic effect. It is a comprehensive category, including needle direction, needle strength, needle depth, selection of specific techniques, length of time between acupuncture treatment sessions, length of needle retention time, and frequency of treatment, all of which play a decisive role in the curative effect and prognosis of diseases.

Due to the unique features of innate immune cells, the role of γδT cells in tumor immunity has gradually attracted more and more attention. Previous studies have found that γδT cells play a dual role in tumor immunology: tumor-promoting and tumor-controlling. The anti-tumor therapy of γδT cell has made remarkable success in clinical application. Especially in recent years, researchers have provided some novel effective ways such as γδT cell exosomes and adoptive chimeric antigen receptor-γδT cell immunotherapy. However, some problems remain to be solved, such as low expansion rate, poor targeting, and tumor microenvironment limiting the effectiveness of γδT immunotherapy. Traditional Chinese medicine is expected to play a positive role in the body immune-enhancing function, promoting the proliferation and activation of γδT cells, and inducing the differentiation of γδT cells. In this review, we summarize the recent research progress and urgent problems of γδT cell in anti-tumor immunotherapy. Moreover, some new strategies of γδT cell for tumor immunotherapy were proposed.

As the novel coronavirus disease 2019 (COVID-19) and its variants continue to rage into the second year of a global pandemic, many success stories of applying Chinese herbal medicine (CHM) to treat COVID-19 patients continue to emerge from China and other part of the world. Herewith, from a systems medicine perspective, the authors analyze those experiences and categorize them into four major treatment principles: (1) focusing on eliminating toxins in the early stage of the disease, (2) tonifying deficiency of the body throughout the entire disease course, (3) treating the affected lung and intestine simultaneously based on visceral interactions, (4) cooling blood and removing blood stasis at the later stage, as well as interpret the rationale of these principles. This is helpful not only in reducing the complexity of promoting the CHM applications to enhance anti-COVID-19 efficacy, but also in ramping out the process of integrating traditional Chinese medicine with modern medical practices.

Objective: This work aimed to present a descriptive analysis of the outcome measures used in clinical trials of traditional Chinese medicine (TCM) for patients with stable angina pectoris, and to provide baseline data for the development of core outcome sets (COSs) for relevant clinical trials. Methods: Medical databases were searched to identify randomized trials of the effects of TCM for the treatment of stable angina pectoris. Outcome measures of each trial were extracted. Descriptive statistics were used to analyze the baseline characteristics of outcomes in clinical trials of TCM. Results: 94 randomized trials (with 9,111 participants) involving 79 different outcomes were identified. The mean number of outcomes was 5 (1-21 per trial). The 5 most commonly reported outcomes were efficacy rate of electrocardiogram, efficacy rate of angina pectoris, efficacy rate of TCM syndrome, fasting lipid indices, and withdrawal rate of nitroglycerin. Several challenges were identified: (1) significant heterogeneity of outcomes and differences in the technique and timing of the measurement of the same outcome; (2) transformation of continuous data into categorical data and presented as such in >90% of trials; (3) few trials on the outcomes associated with the advantages and characteristics of TCM; and (4) selective reporting of outcomes. Conclusions: The outcomes used are excessively heterogenous, and the choice of some outcomes (timing and techniques) for measurement is confusing or inappropriate. Hence, developing and implementing a COS is necessary for greater consistency.

Objective:Lianhua Qingwen combined with Western medicine (LHQW+WM) has been proposed as a viable treatment for coronavirus disease 2019 (COVID-19). Interestingly, umbrella reviews of systematic reviews (SRs), which provide the most comprehensive evidence, are the best evidence in evidence-based medicine. Therefore, an umbrella review of SRs that summarizes and evaluates the efficacy of LHQW+WM for COVID-19 is urgently required. Methods: Overall, 6 databases were used to conduct a comprehensive literature search from inception to January 22, 2022. The corrected covered area (CCA) was used to analyze the overlapping between SRs. Meta-analysis was conducted when that of the included SRs was inappropriate. A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2) was also employed to assess the quality of the included SRs. Results:In total, 12 SRs were identified, which included 12 unique primary studies. The included SRs ranged in quality from moderate to critically low and had an extremely high CCA (36.4%). Compared to conventional treatment, LHQW+WM showed efficacy concerning fatigue recovery[risk ratio (RR) = 1.69, 95% confidence interval (CI): 1.04-2.73, n = 2, I² = 0%], cough recovery (RR = 1.65, 95% CI: 1.09-2.51, n = 3, I² = 39.1%), and overall effective rates (RR = 1.17, 95% CI: 1.07-1.28, n = 3, I² = 17.5%). Conclusion: LHQW+WM may improve the clinical symptoms of patients with COVID-19; however, the results should be interpreted cautiously because of the rigorous processes in the included SRs.

Objective: Baoyuan decoction (BYD) is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests. The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction (MI).
Methods: Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation. Oxygen-glucose deprivation/recovery (OGD/R) model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD.
Results: BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI. Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway.
Conclusions: Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways. They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.

Objective: Sarcopenia causes loss of skeletal muscle and function, thus seriously affecting the physical function and quality of life in the elderly. This article discusses the specific molecular mechanism and ameliorating effects of Tudangshen (TDS) on sarcopenia in elderly rats with type 2 diabetes mellitus (T2DM).
Methods: Elderly Sprague-Dawley (SD) rats were randomly selected and fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish T2DM model. The model rats were stratified and randomly divided into model group, metformin group, TDS high-dose group, TDS medium-dose group, and TDS low-dose group according to blood glucose combined with body weight, and the same batch of old SD rats were set as normal control group. The effects of TDS in an elderly T2DM sarcopenia rat model were evaluated by observing body positions of the rats, analyzing blood biochemistry, testing exercise capacity, and pathologically staining sectioned gastrocnemius muscle tissues. The molecular mechanisms of the effects were analyzed using quantitative real-time polymerase chain reaction and western blotting.
Results: TDS has no statistically significant effect on blood glucose, insulin and glycosylated serum protein in aged rats with T2DM, but it can reduce levels of glycosylated serum protein, total cholesterol, triglycerides, and low-density lipoprotein; it improves pathological changes in rat gastrocnemius muscle tissues, and increases muscle cell activity in elderly rats with T2DM and sarcopenia. TDS also promoted the upregulation of the expression of mammalian target of rapamycin (mTOR)/protein kinase B (PKB/Akt)/phosphatidylinositol 3-kinase (PI3K)/ribosomal protein S6 kinase/eukaryotic initiation factor 4E binding rotein1 mRNA in rats and triggered an increase in corresponding protein levels.
Conclusions: TDS alleviated muscle decline in elderly rats with T2DM by activating the PI3K/AKT/mTOR signaling pathway and regulating the synthesis of corresponding proteins.

Objective: Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) affect the quality of life of elderly individuals. Acupuncture and moxibustion are used in the clinic in China for improving LUTS symptoms due to BPH. However, there is no evidence to suggest which is the best option. We compared the efficacy of acupuncture and moxibustion to provide evidence for clinical decision-making.
Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, and VIP databases were searched from inception to July 2020 to identify the randomized controlled trials (RCTs) of acupuncture and moxibustion for LUTS due to BPH. Two researchers filtered studies and extracted the information independently. This study conducted a network meta-analysis using the Bayesian random method. The interventions ranking was evaluated using the surface under the cumulative ranking curve (SUCRA).
Results: We finally included 40 studies comprising 10 treating therapies and 3655 patients with LUTS caused by BPH. In terms of the International Prostate Symptom Score, maximum urinary flow rate, and quality of life, electroacupuncture (EA) (MD = -3.6, 95% credible interval [CrI] [-5.5, -1.8], very low certainty of evidence; MD = 2.2, 95% CrI [1.1, 3.3], low certainty of evidence; MD = -1.3, 95% CrI [-2.2, -0.43], very low certainty of evidence) may be consistently the optimal treatment compared with other interventions, with SUCRA values of 84%, 81%, and 89%, respectively.
Conclusions: Of all treatments, EA may have the best efficacy with fewer adverse events for LUTS due to BPH. The quality of evidence supporting this result is low to very low certainty of the evidence due to limitations of primary studies; thus, more high-quality RCTs are needed for further evidence.

Objective: This study aimed to develop a core outcome set (COS) for use in future studies of stable angina pectoris (SAP) in traditional Chinese medicine (TCM).
Methods: Systematic literature reviews and qualitative interviews with cardiologists and patients with SAP treated using TCM were conducted to generate a set of outcomes. Outcomes were prioritized by stakeholders via two rounds of an online Delphi survey and face-to-face consensus meetings. Following the final consensus meeting, a final COS was generated.
Results: An initial set of 324 outcomes was identified. A preliminary list of 65 outcomes was employed in the Delphi study. In total, 223 participants from seven stakeholder groups were invited to score outcomes in the first Delphi round: 87 completed round 1 and 47 completed round 2. Thirty-one participants attended the consensus meeting and agreed on a final core set of outcomes comprising six items across four domains: frequency of angina attack, duration of angina attack, Seattle angina questionnaire, total exercise duration in the exercise treadmill test, cardiovascular events, and QT interval on electrocardiography.
Conclusions: The COS developed in this study provides the minimum requirements for measurement and reporting in future TCM clinical trials for the treatment of SAP. The employment of this COS may reduce heterogeneity across trials and facilitate evidence-based decision-making for stakeholders.

Neurodegenerative diseases (NDs) are a major threat to the elderly, and efficient therapy is rarely available. A group of phytochemicals has been shown to ameliorate NDs; however, poor stability, low bioavailability, and reduced drug accumulation in brain tissue limit their application in NDs. Therefore, a targeted drug delivery system is a feasible treatment strategy for NDs. Extracellular vesicles (EVs) possess many favorable bioactivities and are excellent carriers for targeting brain tissue. This review summarizes EVs as novel phytochemical carriers in ND therapy. First, we discuss the current challenges of ND therapy and the therapeutic effects of phytochemicals for NDs. Second, we highlight the ability of EVs to cross the blood-brain barrier and act as drug carriers to enhance the therapeutic efficacy of drugs for NDs. Finally, encapsulation strategies for phytochemicals in EVs are particularly reviewed, as they are critical for obtaining high loading efficacy and stable drug delivery systems. This review provides new insights into EV-based drug delivery systems for improving the therapeutic effect of phytochemicals for ND treatment. Therefore, the release rate and pharmacokinetics of phytochemicals should be well controlled to ensure the therapeutic efficacy of phytochemical-loaded EVs in the brain.

The editorial board of Acupuncture and Herbal Medicine recently convened an academic seminar with a focus on studies regarding the mechanisms mediating acupuncture efficacy and moxibustion action inspired by the 2021 Nobel Prize in Physiology or Medicine. Specifically, Professor Bailong Xiao introduced the Nobel Prize for research on the mechanically activated Piezo ion channel, evaluating the structure of the Piezo channel and its physiological and pathological functions, and proposed a possible role for the Piezo channel in acupuncture mechanical stimulation. Professor Michael Xi Zhu introduced the discovery of the transient receptor potential (TRP) family, reporting that the therapeutic effects of Chinese medicine and acupuncture may be achieved via the TRP family, and that information regarding associations between the meridian and lymphatic systems may have important research and medical value. In addition, Professor Tianle Xu reviewed the history of ion channel research, particularly the physiological and pharmacological effects of non-classical ion channels (eg, the acid sensing ion channel family) and pointed out that the characterization and neural circuits of acupuncture deqi manipulation are important for elucidating the mechanisms of acupuncture actions. Professor Yongming Li similarly proposed that the 2021 Nobel Prize may open the door to disclosing the histological basis of acupuncture and moxibustion and analyzing the main scientific concerns regarding the clinical translation of acupuncture and moxibustion from basic to translational research. Finally, Professor Yi Guo summarized the study progress of the acupoint microenvironment induced by acupuncture over the course of nearly 30 years and put forward the hypothesis that acupuncture may initiate the physical-chemical coupling network by activating ion channel receptors in acupoints via physical and mechanical stimulation. Therefore, we conclude that a primary achievement of the 2021 Nobel Prize in Physiology or Medicine is in helping interpret how acupuncture and moxibustion adjust homeostasis (ie, by activating mechanical and thermal sensation), which is conducive to validating and promoting the clinical efficacy of acupuncture modalities.

Two years after the coronavirus disease 2019 (COVID-19) outbreak, an increasing number of patients continue to suffer from long COVID (LC), persistent symptoms, and/or delayed or long-term complications beyond the initial 4weeks from the onset of symptoms. Constant fatigue is one of the most common LC symptoms, leading to severely reduced quality of life among patients.Ginseng Radix et Rhizoma—known as the King of Herbs in traditional Chinese medicine—has shown clinical anti-fatigue effects. In this review, we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds, with a special focus on anti-viral, immune remodeling, endocrine system regulation, and metabolism, suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC, especially regarding targeting fatigue.

Objective: Moxibustion has been widely used in the prevention and treatment of COVID-19. However, there is no systematic review of current topics and clinical findings on moxibustion for COVID-19. We conducted this scoping review to systematically summarize and analyze the themes and findings of published articles, and to provide an overview of current knowledge and practice of moxibustion for COVID-19.

Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wan Fang Data, and VIP databases were searched from inception until April 2022. The relevant data were presented through bar graphs, structured tables, and figures along with descriptive statistics and analysis. This scoping review was conducted based on the PRISMA-ScR Checklist.

Results: A total of 76 articles were reviewed: 47 reviews, 19 clinical research studies, seven systematic reviews (all were protocols), and three guidelines. All the studies were conducted by Chinese researchers and published from January 1, 2020 to March 14, 2022. The feasibility of moxibustion in the prevention and treatment of mild or moderate COVID-19 is based on the consensus of therapeutic mechanisms and effectiveness. The most adopted approach was the suspended and gentle moxibustion, and the most frequently applied or recommended acupoints were found to be ST36, CV8, CV6, CV4, CV12, GV14, BL13, LI4, ST25, and LR3.

Conclusions: As a convenient and safe traditional Chinese medicine (TCM) therapy with its specific feature, moxibustion has been significantly effective at ameliorating mild or moderate symptoms among COVID-19 patients. Further large-scale, well-designed research and international cooperation are still warranted in clinical evaluations of moxibustion.

Objective: The present study aims to evaluate the in vivo efficacy of YINDARA-4 in improving the symptoms of irritable bowel syndrome (IBS) in a rat model and investigate the impact of YINDARA-4 on potential targets of IBS management, such as the serotonin level in intestinal tissues and the structure and composition of the gut microbiota.

Methods: We developed an IBS rat model by combining stress from maternal separation, acetic acid administration, and restraint. We administered YINDARA-4 water extract to the IBS rat model for 10 consecutive days. The fecal water content, visceral sensitivity, gut microbiota, and serotonin levels in the colonic tissue were then analyzed and compared between the control group, IBS model group, and YINDARA-4-treated groups.

Results: Treatment with YINDARA-4 reversed visceral hypersensitivity in a dose-dependent manner in the experimental rat model of IBS. The relief of visceral hypersensitivity upon treatment with YINDARA-4 involved regulation of the gut microbiota structure and composition, and normalization of elevated serotonin levels in the colon. The decrease in colonic serotonin levels with YINDARA-4 treatment might be associated with a reduction in the abundance of Helicobacter and enrichment of Butyricimonas.

Conclusions: Treatment with YINDARA-4 was beneficial against visceral hypersensitivity in a rat model of IBS. The improved symptoms exhibited in IBS rats were associated with favorably altered gut microbiota and normalization of serotonin levels in the colon.

With its long-term empirical clinical practice and increasing number of health benefits reported, Chinese Materia Medica (CMM) is gaining increasing global acceptance. Importantly, the identification of chemical constituents in vitro and exposed forms in vivo is a prerequisite for understanding how CMM formulae prevent and treat diseases. This review systematically summarizes the exciting and magical journey of CMM components from compound formulae to where they fight, the possible structural transformation of CMM components in vitro and in vivo, and their pharmacological contribution. When a decoction is prepared, significant chemical reactions are observed, including degradation and production of polymers and self-assembling supramolecules, leading to the construction of a component library with diverse decoction structures. After ingestion, compounds pass through the intestinal and blood-brain barriers and undergo a more wonderful journey involving the gut microbiota, microbial enzymes, and endogenous drug-metabolizing enzymes (mainly liver enzymes). At this stage, they are modified and assembled into novel and complex compounds, such as newly generated metabolites, conjugates, and self-assembling superamolecules. This review might provide a strategic orientation to explore the active compounds of CMM formulae in vivo.

Objective:To systematically review the clinical practice guidelines (CPGs) for the treatment of patients with coronavirus disease 2019 (COVID-19) using Chinese herbal medicine (CHM), assess the methodological quality as well as clinical credibility and implementability of specific recommendations, and summarize key recommendations.

Methods:As of April 2022, we conducted a comprehensive search on major electronic databases, guideline websites, academic society websites, and government websites to assess the methodological quality and clinical applicability of the included CPGs using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and Evaluation-Recommendations EXcellence (AGREE-REX) instructions, respectively.

Results:The search yielded 61 CPGs, which were mostly published in 2020; moreover, 98.4% of the CPGs were published in China. Only five CPGs achieved a high-quality AGREE II rating; further, six CPGs could be directly recommended, with most of the CPGs still showing much room for improvement. CPGs had a low overall score in the AGREE-REX evaluation, with the domains of clinical applicability, values and preferences, and implementability being standardized in 21.80%β±β12.56%, 16.00%β±β11.81%, and 31.33%β±β14.55% of the CPGs, respectively. Five high-quality CPGs mentioned 56 Chinese herbal formulas. Half of the recommendations had moderate or strong evidence level in the GRADE evaluation. The most frequently recommended herbal medicines were Lianhua Qingwen granule/capsule and Jinhua Qinggan granule; however, the strength of recommendation for each prescription varied across CPGs and populations.

Conclusions:The overall quality of current CPGs for COVID-19 for CHM still needs to be improved; moreover, the strength of the evidence remains to be standardized across CPGs.

Objective: Pinellia Tuber, the dried tuber of Pinellia ternata, is widely used in Japanese Kampo medicines and traditional Chinese medicines. The unprocessed Pinellia Tuber is known to cause very strong acrid irritation at oral and laryngopharynx mucosa. Recent studies have shown that the sharp needle-like crystals called raphides, that are composed of calcium oxalate and proteins, are the main causative substances of the irritation. Ginger, the rhizome of Zingiber officinale, has been used in the processing to reduce the acridity of Pinellia Tuber since before the sixth century, however, the mechanisms of reducing acridity have not been scientifically proved yet.
Methods: We developed the raphides denaturation assay (RDA) to quantify the degree of denaturation in the raphides to cause irritation. By their lipophilic characters, the raphides could be extracted in petroleum ether (PE) layer from powdered Pinellia Tuber suspended in water, and the contents of the raphides in PE layer were measured by the absorbance. By this assay, we conducted the activity-guided fractionation from the boiling water extract of ginger to find the ingredients to denature the raphides. We also conducted the gustatory tests to detect the change of the irritation of the denatured raphides.
Results: The treatment of powdered Pinellia Tuber suspension with ginger extract reduced the distribution of raphides in PE layer in RDA in a concentration-dependent manner. The activity-guided fractionation using RDA revealed that oxalic acid was the main active ingredient in ginger extract to denature the raphides of Pinellia Tuber. Oxalic acid reduced the lipophilicity of the raphides in the thermo-, time-, and concentration-dependent manners, and its activity was affected by pH. The treatment of powdered Pinellia Tuber suspension with oxalic acid significantly reduced its acrid irritation in gustatory test in human.
Conclusions: We found that oxalic acid is the main active ingredient in ginger to reduce the acrid irritation of Pinellia Tuber.

Vaccination is a major achievement that has become an effective prevention strategy against infectious diseases and active control of emerging pathogens worldwide. In response to the coronavirus disease 2019 (COVID-19) pandemic, several diverse vaccines against severe acute respiratory syndrome coronavirus 2 have been developed and deployed for use in a large number of individuals, and have been reported to protect against symptomatic COVID-19 cases and deaths. However, the application of vaccines has a series of limitations, including protective failure for variants of concern, unavailability of individuals due to immune deficiency, and the disappearance of immune protection for increasing infections in vaccinated individuals. These aspects raise the question of how to modulate the immune system that contributes to the COVID-19 vaccine protective effects. Herbal medicines are widely used for their immune regulatory abilities in clinics. More attractively, herbal medicines have been well accepted for their positive role in the COVID-19 prevention and suppression through regulation of the immune system. This review presents a brief overview of the strategy of COVID-19 vaccination and the response of the immune system to vaccines, the regulatory effects and mechanisms of herbal medicine in immune-related macrophages, natural killer cells, dendritic cells, and lymphocytes T and B cells, and how they help vaccines work. Later in the article, the potential role and application of herbal medicines in the most recent COVID-19 vaccination are discussed. This article provides new insights into herbal medicines as promising alternative supplements that may benefit from COVID-19 vaccination.

An increasing number of practitioners are using acupuncture methods such as wrist-ankle acupuncture (WAA) to treat pain. We aimed systematically to evaluate the effects of WAA on cancer pain, primary pain, chronic musculoskeletal pain and pathological neuralgia pain. Nine electronic databases were searched for randomized controlled trials (RCTs) on WAA from inception of the data base to July 31, 2022. RCTs within the inclusion and exclusion criteria were included in the study. Outcomes included pain score, clinical efficacy (overall efficiency), and occurrence of adverse events. The risk of bias was evaluated using the Cochrane Collaboration criteria and meta-analysis was performed using RevMan 5.4.1 software to determine the effect of WAA intervention and statistical significance was set a P < 0.05. A total of 19 RCTs were included in the meta-analysis including 1,380 participants, consisting of 673 who had received WAA alone or in combination with other treatments (WAA group, WG) and 707 who did not receive WAA (control group, CG). Subgroup analyses were performed according to different chronic pain types and occurrence of adverse events of WAA versus oral or non-oral drug therapy. The WG had better analgesic effects on various types of chronic pain than CG (P < 0.00001) and clinical efficacy (P < 0.00001). Additionally, WAA was shown to be safer than oral medication (P = 0.09). Therefore, WAA has good analgesic efficacy for several types of common chronic pain alone and in combination with other therapies, and it is safer than oral medication. However, more high-quality randomized controlled trials are needed in the future to support this evidence.

Objective: To investigate the inhibitory effect and mechanism of Wei Chang An pill (WCA) on ulcerative colitis (UC).
Methods: A 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC model was established, and WCA was administered orally for 1 week. Body weight, colon length, disease activity index (DAI) score, and colon mucosa damage index (CMDI) score were recorded. Cytokine expression in lipopolysaccharide (LPS)-stimulated THP-1 cells was evaluated to determine the anti-inflammatory effects of WCA and its active ingredients. Immunohistochemistry and immunofluorescence were performed to detect the expression of epithelial-mesenchymal transition (EMT) markers E-cadherin and vimentin in rat UC and WCA groups, and in Caco-2 cells stimulated with conditioned medium (CM) from THP-1 cells, with or without LPS or WCA.
Results: WCA significantly inhibited body weight loss, decreased DAI and CMDI scores, blocked colon length shortening, and improved histological damage in UC rats. Furthermore, both myeloperoxidase (MPO) activities and cytokine expression in UC tissues were significantly suppressed by WCA as well. In THP-1 cells, the mRNA expression of interferon-inducible protein (IP)-10, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and NF-κB inhibitor α (IκBα) was significantly suppressed by WCA and its active ingredients. E-cadherin expression in UC rats and CM-stimulated Caco-2 cells was downregulated and vimentin expression was upregulated, whereas both were blocked when administered with WCA.
Conclusions: Our data showed that WCA alleviated UC progression by inhibiting inflammation-induced EMT progression.

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by recurrent abdominal pain, bloating, and irregular bowel movements with complex pathogenesis. Due to its high prevalence and reoccurring symptoms, it seriously impacts patients' quality of life. One of the causes of IBS is turbulence of gastrointestinal motility and intestinal secretion due to dysfunction of the autonomic nervous system (ANS), which the includes the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system. Current research has proven that acupuncture, a traditional Chinese therapy, is useful and effective for treating IBS. The ANS is a key pathway for bidirectional information transmission between the gastrointestinal tract and the central nervous system, which plays an important role in IBS treatment with acupuncture. Research on the mechanisms of acupuncture for IBS is receiving more attention, and the use of contemporary methods has made significant progress. Evidence suggests that acupuncture may mitigate the negative consequences of IBS, as seen by reduced inflammatory signaling, neurotransmitter levels in the colon and central neural tissues, and balanced gut flora. We review and discuss acupuncture's possible mechanisms of action for IBS treatment via the ANS, including modulation of gastrointestinal motility, improvement of visceral hypersensitivity, and innervation of the gut-brain-microbiota axis. Our review demonstrates the available evidence for acupuncture treatment of IBS in clinical settings; however, we also observe that the relationship between the ANS and the gut-brain-microbiota axis is unclear, and further research is needed.

Objective: As an injection made from traditional Chinese medicine, Shuxuetong (SXT) injection is used for the treatment of ischemic stroke. Hypoxanthine is regarded as one of its potential quality markers. The purpose of this study is to lay the foundation for the quality control of SXT injection by the analysis of the quantitation and pharmacokinetic behavior of hypoxanthine.
Methods: A quantitative method of hypoxanthine in SXT injection based on standard addition method by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established for the first time. On the other hand, a determination method of hypoxanthine in rat plasma samples after administration of SXT was also successfully established based on LC-MS/MS.
Results: It was found that the content of hypoxanthine was higher using conventional liquid-mass spectrometry technology compared to the application of LC-MS/MS combined standard addition method in the same batch of SXT injection. The ratio of low, medium and high doses of intravenous SXT were 1:2:4, and the AUC_0-t was (848.34 ± 324.53) μg·h/L, (1483.94 ± 497.74) μg·h/L, and (3074.84 ± 910.29) μg·h/L, respectively. AUC_0-t shows a good linear dose-dependent relationship.
Conclusions: The influences of endogenous substances tend to be eliminated by calibrating the concentration level of the target compound by the introduction of the standard addition method. The added allopurinol could inhibit the conversion of the target compound, and ensure the accuracy of the detection during the pharmacokinetic studies. “Blank biological matrix” obtained from the pretreatment of blank plasma successfully distinguished endogenous and drug-derived hypoxanthine. There is a good linear relationship between the blood concentration of intravenous hypoxanthine and the dosage of administration. Similarly, there was no drug accumulation in the multiple medium-dosage group, which is similar to the pharmacokinetic characteristics of the single medium-dosage group.

Coronavirus disease 2019 (COVID-19) is a major disease that threatens human life and health. Its pathogenesis is complex and still not fully clarified. The clinical treatment is mainly supportive and lacks specific treatment methods. Acupuncture treatment can inhibit immune inflammatory reactions, neuroinflammatory reactions, oxidative stress levels, and hypothalamus-pituitary-adrenal (HPA) axis activity, improve lung function, and relieve migraine, fatigue, anxiety, and depression. However, whether acupuncture treatment is suitable for treating these symptoms in patients with COVID-19 still needs to be investigated. For this review, the literature was systematically searched for multiple databases to summarize the mechanisms of acupuncture treatment for COVID-19-related symptoms and complications. A complex network analysis of acupoints and symptoms was also performed to clarify acupoint selection in the acupuncture treatment of symptoms related to COVID-19. The evidence indicates that acupuncture can improve the respiratory, digestive, nervous, and mental and psychological symptoms related to COVID-19 by inhibiting immune inflammatory reactions, regulating intestinal flora, mitochondrial function, oxidative stress level, cardiomyocyte apoptosis, neurotransmitter release, and HPA axis activity, and alleviating basic diseases such as diseases of the vascular system. Acupuncture can improve various clinical and concomitant symptoms of COVID-19; however, its mechanism of action is complex and requires further study.