Traditional Chinese Medicine Clinics Research Articles

Oral bacteriome and mycobiome of patients with idiopathic membranous nephropathy with different tongue coatings treated with a Chinese herbal formula

Ethnopharmacological relevanceMoshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. Aim of the studyIn this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. Materials and methodsWe enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. ResultsThe therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. ConclusionThe regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

Part-of-Speech Tagging for Traditional Chinese Medicine Clinical Pulse Feeling and Palpation Information Based on Hidden Markov Model Prompt-Tuning

This paper proposes a Traditional Chinese Medicine Clinical Pulse Feeling and Palpation Information part-of-speech tagging method based on Hidden Markov Model Prompt-Tuning, aimed at addressing the challenges of scarce annotated samples and the issue of words with multiple parts of speech in Traditional Chinese Medicine Clinical Pulse Feeling and Palpation Information part-of-speech tagging tasks. By designing specific prompt templates, this method transforms the downstream task into a cloze task for the pretrained language model during its pretraining phase, thereby bridging the gap between pretraining and fine-tuning objectives and enhancing the knowledge representation ability of the pretrained language model for downstream tasks. This approach also integrates the part-of-speech information of adjacent words into the prompt templates and uses the Hidden Markov Model to model the dependencies between adjacent words' parts of speech, effectively improving the overall performance of the model in the Traditional Chinese Medicine Clinical Pulse Feeling and Palpation Information part-of-speech tagging task, particularly in identifying words with multiple parts of speech. Furthermore, empirical evidence demonstrates the outstanding performance of the proposed method in this part-of-speech tagging task, achieving an F1 score of up to 85.52%.

A multi-center cross-sectional study of Chinese Herbal Medicine-Drug adverse reactions using active surveillance in Singapore’s Traditional Chinese Medicine clinics

BackgroundThis study aimed to investigate the rates and causality of patient-reported adverse events (AEs) associated with concomitant Chinese Herbal Medicine (CHM) and Western Medicine prescription drug (WMPD) consumption through active surveillance in Singapore’s Traditional Chinese Medicine (TCM) clinics.MethodsA cross-sectional study was conducted at five TCM clinics across Singapore from 8th May till 8th July 2023. Patients were screened to determine rates of CHM and WMPD consumption, and then interviewed if an AE was reported. An expert committee assessed the AE reports to determine causality. Along with descriptive statistics, odds ratios were calculated to determine AE occurrence likelihoods for patients who consumed both CHM and WMPD compared to CHM consumption alone.Results1028 patients were screened and 62.65% of them reported concurrent CHM-WMPD consumption. Patients who consumed CHM and WMPD were 3.65 times more likely to experience an AE as compared to CHM consumption alone. 18 AE reports were adjudicated, with most AEs deemed unlikely due to CHM consumption.ConclusionsA large proportion of patients consumed CHM and WMPD concurrently, thus increasing their risk of experiencing AEs compared to those consuming CHM only. Active surveillance is applicable for detecting AEs, collecting data for causality assessment, and analysis.

Usage Patterns of Traditional Chinese Medicine for Patients with Bipolar Disorder: A Population-Based Study in Taiwan.

Patients with bipolar disorder (BD) receive traditional Chinese medicine (TCM) for clinical needs unmet with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD. Data for a total of 12,113 patients with BD between 1996 and 2013 were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000). The chi-square test was used for categorical variables, and the independent t-test was used for continuous variables. A p-value less than 0.05 indicated significance. One thousand three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group (n = 1053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herbs and herbal formulae. Physicians need to be aware of the use of TCM in patients with BD.

Unlocking the hidden potential: Enhancing the utilization of stems and leaves through metabolite analysis and toxicity assessment of various parts of Aconitum carmichaelii

Ethnopharmacological relevanceAconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves. Aim of the studyUsing plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications. Materials and methodsUHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites. ResultsA total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers. ConclusionGiven the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development.

Mechanism of Nardostachyos Radix et Rhizoma–Salidroside in the treatment of premature ventricular beats based on network pharmacology and molecular docking

To analyse the mechanism of Nardostachyos Radix et Rhizoma–Salidroside in the treatment of Premature Ventricular Brats by using network pharmacology and molecular docking and to provide the basis for developing the use of experimental and clinical traditional Chinese medicine. The chemical compositions of Nardostachyos Radix et Rhizoma and Salidroside were determined, and their related targets were predicted. The disease-related targets were obtained by searching the common disease databases Genecards, OMIM, Drugbank and DisGeNET, and the intersection between the predicted targets and the disease targets was determined. Then using the STRING database to set up the protein‒protein interactions (PPIs) network between Nardostachyos Radix et Rhizoma–Salidroside and the common targets of PVB. An “herb-ingredient-target” network was constructed and analyzed by Cytoscape3.7.2 software. Using the metascape database to analysis the predicted therapeutic targets based on the GO and KEGG. Finally, molecular docking technology was used toconfirm the capacity of the primary active ingredients of the 2 herbs to bind to central targets using the online CB-Dock2 database. 41 active components of Nardostachyos Radix et Rhizoma–Salidroside were detected, with 420 potential targets of action, with a total of 1688 PVB targets, and the top 10 core targets of herb-disease degree values were AKT1, TNF, GAPDH, SRC, PPARG, EGFR, PTGS2, ESR1, MMP9, and STAT3. KEGG analysis indicated that its mechanism may be related to the calcium signalling pathway, cancer signalling pathway, AGE-RAGE signalling pathway and other pathways. Molecular docking suggested that main of the active ingredients of the Nardostachyos Radix et Rhizoma–Salidroside pairs were well bound to the core targets. Based on novel network pharmacology and molecular docking validation research methods, we revealed for the first time the potential mechanism of Nardostachyos Radix et Rhizoma–Salidroside in PVB therapy.

Insights into the inhibition of stomach cancer MKN45 cell growth by Poria cocos ethanol-soluble extract based on MAPK/PI3K signaling pathways and components cell fishing

Ethnopharmacological relevancePoria cocos F.A. Wolf is an edible fungus with forming sclerotia, which has the effects of promoting diuresis, exuding dampness, invigorating the spleen, and regulating the stomach. P. cocos has a high application in the clinic of traditional Chinese medicine, and some studies have indicated that P. cocos has a good effect on tumor diseases. According to ancient records and modern studies, P. cocos wine offers beneficial effects in terms of strengthening tendons and bones and anti-tumor effects. Aim of the studyTo understand the substance composition of P. cocos ethanol-soluble extract (PESE) and then further study the effect and potential mechanism of PESE components on gastric cancer. Materials and methodsIn vitro and in vivo experiments were performed to detect the cell activity and apoptotic condition. Differential expression analysis and pathway enrichment were performed based on transcriptomics and were verified by real-time polymerase chain reaction and western blotting. The mice of the stomach cancer tumor model were randomly categorized into three groups. The weight and tumor volume of the mice were measured, and the pathological characteristics of tumor tissue and immunohistochemical changes were determined. Then, the main active components of PESE were detected by MKN45 cell fishing. ResultsIn vitro experiments showed that PESE inhibited the proliferation of MKN45 cells, but it did not induce apoptosis. Based on the transcriptome and western blotting results, the inhibition of MKN45 proliferation by PESE may be influenced by mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase–protein kinase B (PI3K-Akt) signaling pathways. In vivo experiments showed that PESE inhibited tumor growth in mice and caused partial necrosis of tumor cells but had no toxic effect on mice. Cell fishing identified nine triterpenoids of P. cocos as the major active components of PESE. ConclusionsThe results indicated that PESE has a significant inhibitory effect on stomach cancer, and its mechanism probably commonly affects the MAPK and PI3K-Akt signaling pathways, which could be due to the triterpenoid components.

DIA-based serum proteomics revealed the protective effect of modified siwu decoction against hypobaric hypoxia

Ethnopharmacological relevanceSiwu decoction (SWD) is a common traditional formula for nourishing blood, and its derived formulas are also widely used in traditional Chinese medicine (TCM) clinic. However, the protective effects of SWD and its derived formulas on blood deficiency and blood stasis caused by rushing to the plateau are rarely reported, and the underlying mechanism has not been fully elucidated. Aim of the studyThis study explores the pharmacological effects and mechanisms of modified siwu decoction (MSWD) adding Persicae Semans (Prunus persica (L.) Batsch) and Carthami Flos (Carthamus tinctorius L.) against hypobaric hypoxia (HH). The acute toxicity of MSWD was also evaluated to further validate the potential of MSWD as a therapeutic candidate for HH. Materials and methodsHypoxic models of C57BL/6 J and KM male mice were used to evaluate the pharmacological effect of MSWD. 2 μL serum sample of C57BL/6 J mice was digested into peptide mixtures and analyzed with DIA mode on an Orbitrap Fusion Lumos mass spectrometer after LC separation. The peptide and protein identifications were limited to a 1% FDR. Screening of differential expressed proteins, correlation analysis, hierarchical clustering analysis, principal components analysis and Mfuzz analysis were all performed by R packages. The protein−protein interaction network was analyzed using the STRING website and constructed with Cytoscape software. ResultsMSWD showed a protective effect against acute hypoxia exposure through increasing the number of red blood cells and improving hemodynamics indexes in mice. Meanwhile, the biochemical results showed that MSWD could reduce the inflammation and oxidative stress, reduce the content of organ injury biomarkers and significantly improve the high-intensity exercise ability of mice. Subsequently, serum DIA proteomic results revealed significant changes in proteomic characteristics after MSWD intervention. Specifically, proteins related to oxidative stress and ubiquitin-proteasome system, such as Sod1, Gstp1, Vcp and Usp14, were down-regulated after MSWD intervention, suggesting that the protective effect of MSWD involved the reduction of oxidative stress and energy expenditure. MSWD also intervened in energy metabolism and lipid metabolism processes by altering the expression levels of Eno1, Sphk1 and Apoa1 to ameliorate hypoxia-induced disorders. At the same time, MSWD acute toxicity test showed no obvious toxicity. ConclusionsMSWD has a good protective effect against HH by ameliorating hypoxia-induced disorders of energy and lipid metabolism, supporting MSWD as a safe drug candidate for the prevention and treatment of acute hypoxia fatigue.

Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis.

Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 μM) or a COX-2 inhibitor Celecoxib (1, 3, 9 μM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.

Cantharidin induces apoptosis of human triple negative breast cancer cells through mir-607-mediated downregulation of EGFR

BackgroundTriple negative breast cancer (TNBC) is a major subtype of breast cancer, with limited therapeutic drugs in clinical. Epidermal growth factor receptor (EGFR) is reported to be overexpressed in various TNBC cells. Cantharidin is an effective ingredient in many clinical traditional Chinese medicine preparations, such as Delisheng injection, Aidi injection, Disodium cantharidinate and vitamin B6 injection. Previous studies showed that cantharidin had satisfactory pharmacological activity on a variety of tumors. In this study, we aimed to study the therapeutic potential of cantharidin for TNBC treatment by targeting EGFR, and expound its novel regulator miR-607.MethodsThe effect of cantharidin on breast cancer in vivo was evaluated by 4T1 mice model. Then the effects of cantharidin on TNBC cells was assessed by the MTT, colony formation, and AnnexinV-PE/7AAD staining. Cantharidin acts on EGFR were verified using the cell membrane chromatography, RT-PCR, Western blotting, MTT, and so on. Mechanistic studies were explored by dual-luciferase report assay, RT-PCR, western blotting, and immunofluorescence staining assay.ResultsCantharidin inhibited TNBC cell growth and induce apoptosis by targeting EGFR. miR-607 was a novel EGFR regulator and exhibited suppressive functions on TNBC cell behaviors. Mechanistic study showed that cantharidin blocked the downstream PI3K/AKT/mTOR and ERK/MAPK signaling pathway.ConclusionOur results revealed that cantharidin may be served as a potential candidate for TNBC treatment by miR-607-mediated downregulation of EGFR.Graphical

Influence of Gegenqinlian decoction on pharmacokinetics and pharmacodynamics of saxagliptin in type 2 diabetes mellitus rats.

Gegenqinlian decoction (GQD) is a classic prescription of traditional Chinese medicine (TCM), which originated from Shanghanlun. The combination of GQD and hypoglycemic drugs (saxagliptin, Sax, metformin) is often used to treat Type 2 diabetes mellitus (T2DM) in TCM clinics. However, the herb-drug interactions (HDIs) between GQD and hypoglycemic drugs are still unclear. In order to determine the safety of the combination, we assessed the influences of GQD on the pharmacokinetics and pharmacodynamics of Sax in T2DM rats. The plasma concentration of Sax (5mg/kg) pretreated with GQD (freeze-dried powder, 1.35g/kg) or not was determined by high-performance liquid chromatography (HPLC), and pharmacokinetics parameters were calculated. The influence of GQD on the pharmacodynamics of Sax was investigated by detecting the levels of weight, (see abbreviations list) OGTT, TC, TG, LDL-C, HDL-C, FBG, FINS, HOMA-IR, QUICKI, AST, ALT, and the liver coefficient. The Cmax , AUC0-t ,and AUC0-∞ of Sax increased significantly in the combination group whether in normal or T2DM rats. The results of pharmacodynamics showed that the weight of rats in each treatment group increased. FBG, TC, TG, LDL-C, and HOMA-IR decreased, HDL-C, FINS, and QUICKI increased significantly (p<0.05) compared with the model control group. The result showed that the combination of GQD and Sax could not only improve the hypoglycemic effect but also increase the plasma exposure of Sax. The potential HDIs between GQD and Sax should be taken into consideration in clinics. Moreover, for the complexity of the human compared with experimental animals, as well as genetic differences, the in-depth study should be carried out to assess the uniformity of the pharmacokinetics and pharmacodynamics between rats and humans.

Total flavonoids of Hippophae rhamnoides L. improves type 2 diabetes symptoms in rats through down-regulating of the DAG/PRKCA/MAPK10/p65/TNF-α signalling pathway

Ethnopharmacological relevanceDry mature fruits of Hippophae rhamnoides L. (HRL), Elaeagnaceae, have traditional functions of invigorating spleen and improving spleen insufficiency. Traditional Chinese medicine (TCM) clinics have been proved that HRL is in favor of diabetes treatment. Modern pharmacological studies demonstrated that total flavones of Hippophae rhamnoides (TFH) are the main substance for HRL to develop anti-inflammation and anti-diabetes functions. However, chemical features, active ingredients and anti-diabetes pharmacological mechanism of HRL still remain unclear. Aim of the studyKey targets and metabolites in anti-type-II diabetes mellitus (T2DM) of TFH have been explored based on AGE-RAGE signaling pathway in diabetic complications. The anti-T2DM mechanism of TFH has been elaborated from comprehensive perspectives, including target prediction, metabolites, potential metabolic pathways, and so on. Materials and methodsIn this study, a qualitative test of chemical composition of HRL was carried out based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The anti-T2DM targets and pathways of HRL were predicted through network pharmacological approach. The T2DM rat model was induced by high-fat and high-glucose diet combined with streptozotocin (STZ). The T2DM model was evaluated through fasting blood glucose level, body weight, serum biochemical indicators, insulin levels and homeostatic model assessment of insulin resistance. The key metabolic pathways were screened through the correlation between metabolites and key targets. Finally, the quantitative analysis of key targets and metabolites was verified through experiments. ResultsAfter TFH intervention, the fasting blood-glucose level of T2DM rats induced by high-fat and high-glucose diet combined with streptozotocin (STZ) was downregulated significantly, while body weight, serum liquid level, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) were improved. According to ELISA, Western blotting (WB) and reverse transcriptase polymerase chain reaction (RT-PCR), TFH significantly downregulates expression levels of diglyceride (DAG)-activated protein kinase C (PRKCA), mitogen activated protein kinase 10 (MAPK10), human nuclear factor κB subunit p65 (NF-κB p65) and tumor necrosis factor-α (TNF-α) in pancreas of STZ-induced rats. ConclusionsTFH downregulates expressions of PRKCA, MAPK10 and p65 TNF-α as well as level of the key metabolite DA in the DAG/PRKCA/MAPK10/TNF-α/p65 pathways, improves lipid metabolism disorder, inhibits inflammatory response and thereby relieves symptoms of T2DM.

Study on the substance basis of the efficacy of eucommiae cortex before and after salt processing for the treatment of kidney-yang deficiency syndrome based on the spectrum-effect relationship

Ethnopharmacological relevanceKidney-Yang deficiency syndrome (KYDS) is one of the common diseases of the elderly and closely related to the ageing of the body, it has a major impact on the quality of life of the patient. Eucommiae Cortex (EC) is the dried bark of Eucommia ulmoides Oliv. Which has the effect of tonifying the liver and kidneys, strengthening the muscles and bones. In Traditional Chinese Medicine clinics, EC is commonly used in the treatment of KYDS, but the material basis for the improvement of its efficacy in treating KYDS after salt processing remains unclear. Aim of the studyThis study aimed to find the main active ingredients that could improve the treatment of KYDS efficacy of EC after salt processing. Materials and methodsFirstly, the fingerprints of raw and salt-processed EC were established to determine the common components by using HPLC, and then an experimental study on the treatment of KYDS efficacy was carried out to compare the difference in the efficacy between raw and salt-processed EC. Thirdly, the spectrum-effect relationship of chemical components and pharmacodynamic indexes was established by using Grey Relational Analysis and Entropy Method. Finally, the network pharmacology and molecular docking technique was used to verify the kidney tonifying effect of the active ingredients of EC. ResultsAccording to the results of the analysis of hormonal index levels on the hypothalamic-pituitary-target gland axis and the extent of renal lesions, the therapeutic effect of EC on KYDS was mainly reflected in the regulation of the Adrenocorticotropic hormone, Corticosterone in the hypothalamic-pituitary-adrenal axis and Tri-iodothyronine, Tetra-iodothyronine in the hypothalamic-pituitary-thyroid axis, moreover the therapeutic effect of salt-processed EC was stronger than that of raw EC. The pharmacologically active ingredients that improved its treatment of KYDS efficacy after salt processing were peak 1 (geniposidic acid), peak 2 (chlorogenic acid), peak 5 (geniposide), peak 6 (genipin), peak 7 (pinoresinol diglucoside) and peak 11 (hyperoside). Meanwhile, the results of network pharmacology and molecular docking showed that the 6 active ingredients could exert kidney tonic effects through multiple signaling pathways by acting on core targets such as AKT1 and PTGS2. ConclusionAs far as we known, this was the first time to establish and compare the spectrum-effect relationship between raw and salt-processed EC, which laid the foundation for the pharmacokinetics studies of EC and provided a reference for future EC studies.

Research on Changes and Response Strategies of Health Human Resource Demands in CHSC in the aftermath of the COVID-19 Pandemic

Community health service centers (CHSC) are the first line of defense for national health. In the post-epidemic era, CHSC need to effectively play the role of the grassroots "outpost." In addition to daily medical and public health work, they should also strengthen joint prevention and control to consolidate the achievements of epidemic prevention and control. Under the new situation, the demand for talent in CHSC has also changed, and the construction of its talent team faces many challenges. This article collects relevant materials and data to analyze the changes in the work content of health personnel in CHSC in the post-epidemic era, and analyzes the changes in talent demand and key problems under the new situation, providing strategies to strengthen the construction of talent teams in CHSC in the new era. Key problems in CHSC in the post-epidemic era include unreasonable structure of health personnel, insufficient allocation of health personnel, unclear rights and responsibilities, and rigid talent training models. To improve the professional level and governance ability of health personnel in CHSC, optimize the working environment of health personnel, and address the issue of scarce positions, strategies are proposed such as relaxing recruitment conditions for scarce positions, encouraging the establishment of traditional Chinese medicine clinics, fully leveraging social collaborative forces, promoting diversified training for the capacity building of grassroots health personnel, and establishing new talent development platforms.

Discovery of Elaphuri Davidiani Cornu-specific peptide biomarkers by peptidomics analysis-based method.

Elaphuri Davidiani Cornu (EDC) is the antler of the male Père David's deer, which has been reported to have multiple biological activities, and its use as a traditional Chinese medicine (TCM) in China has been known for thousands of years. However, EDC is difficult to distinguish from other related species-derived antlers in powder or extract form in TCM clinic use, such as Cervus elaphus Cornu (CEC) and Cervus nippon Cornu (CNC), both derived from Cervidae and easily confused with EDC. In this study, a strategy using peptidomics combined with mathematics set analysis was used to identify EDC-specific peptide biomarkers, and four specific peptide biomarkers (Pep-E1-E4) were identified and validated. Pep-E1, Pep-E3, and Pep-E4 could be exclusively detected in EDC samples, with relative peak areas of 0.298±0.060, 0.039±0.015, and 0.037±0.008, whereas Pep-E2 showed relative peak area of 0.516±0.101 in EDC, 0.132±0.026 in CEC, and 0.136±0.047 in CNC samples, respectively. These four peptides are applicable to distinguish EDC from CEC and CNC, which is of great significance for the quality control of EDC.

Trehalose and brassinolide enhance the signature ingredient accumulation and anti-oxidant activity in the hairy root cultures of Polygala tenuifolia Willd.

Polygala tenuifolia Willd. is a commonly used clinical traditional Chinese medicine with a variety of biological activities. Hairy root cultures of medicinal plants are considered as a source of active constituents for pharmaceutical industries. In this study, P. tenuifolia hairy root cultures (PTHRCs) were established by induction of four Rhizobium rhizogenes, including ATCC15834, LBA9402, C58C1 and ACCC10060. The contents of active ingredients such as polygalaxanthone III, 3′,6-disinapoylsucrose, onjisaponin B, onjisaponin F, polygalacic acid and senegenin were detected in the hairy roots by high performance liquid chromatography (HPLC). Forty-five day-old leaf disc of P. tenuifolia sterile seedlings were prepared for explants, the highest hairy root transformation rate reached 85.83 % by using R. rhizogenes C58C1 co-cultured for 3 d with an optical density of 1.5 at 600 nm, coupled with 200 µM acetosyringone added in the solid culture medium. Meanwhile, the conditions of PTHRCs were optimized for the xanthones, saponins, and oligosaccharides components production. The results showed that the dry weight of the hairy roots reached its maximum of 0.44 g/flask (9.26 fold than that of the control) under the optimal culture conditions: 6,7-V medium, 3 % sucrose (m/v), pH 5.8, and 6 week-old PTHRCs, and the six signature ingredients in the hairy roots accumulated massively under the same condition simultaneously. Furthermore, trehalose and brassinolide were found to significantly promote the biomass and active ingredients biosynthesis in the hairy root cultures. The content of polygalaxanthone III was 8.92 folds higher than the description in the Chinese Pharmacopoeia (2020 year version) induced by 10 µM trehalose, while 1 × 10−12 M brassinolide treatment promoted onjisaponin F accumulation at 33.63 mg/g (dry weight) in PTHRCs. In addition, total phenolics, flavonoids, and antioxidant activity of PTHRCs extracts were significantly increased induced by trehalose (5 µM) and brassinolide (1 ×10−10 M), respectively. This is the first report on the systematic construction of PTHRCs and trehalose and brassinolide as effective elicitors for polygalaxanthone III, 3′,6-disinapoylsucrose, onjisaponin B, onjisaponin F, polygalacic acid and senegenin production in PTHRCs. The results demonstrated that PTHRCs can be used to produce active constituents in pharmaceutical and nutraceutical fields.

Clinical Retrospective Analysis of Cold and Heat Diagnosis of Traditional Chinese Medicine by Application of Infrared Thermal Imaging Technology

Objective: Exploring the application of infrared thermal imaging technology in Traditional Chinese Medicine (TCM) diagnosis of cold and heat by comparing the cold and heat of TCM clinical dialectics with the cold and heat objectively measured by infrared thermal imaging technology. Methods: First, there were 77 patients from the Prevention and Treatment Center of Guangdong Hospital of TCM selected to analyze their clinical information retrospectively. Then, transforming the temperature index measured by infrared thermal imaging technology into the cold and heat deviation index, which can reflect the cold and heat of traditional Chinese medicine. Finally, a Correlation analysis was made between patients' cold and heat deviation index, and clinical symptoms, the type of cold and heat syndrome diagnosed by doctors. Results: The cold and heat deviation index of the outer, upper outer, and lower outer parts of the patients was significantly lower than that of the inner, upper inner, and lower inner parts of the patients and the difference in the mean values of the three groups was 0.06, 0.07 and 0.03, respectively. In all parts of the subjects, the coincidence rate of clinical dialectics of cold and cold and heat deviation index less than 0 (belonging to cold) was 70.17%. In patients with fatigue symptoms, the cold and heat deviation index of the lower inner part, the upper inner part, and the inner part was significantly higher than that of the lower outer part, the upper outer part, and the outer part. Conclusions: The pattern of human torso region division combined with the cold and heat deviation index can be used to reflect the quantitative understanding of cold and heat in the TCM clinic. Quantifying the variation of cold and heat according to the trend of torso regional temperature deviation can explain the pathogenesis of some elementary symptoms closely related to cold and heat. As a quantitative index of TCM cold and heat, the offset index can be proof for visualization, objectification, and quantification, combined with doctors' judgment, which can an effective auxiliary diagnostic means of TCM to a certain extent.

When Patients' Assessments of Treatment for Subjective Symptoms are At Odds with Authoritative Assessments in the Biomedical Literature: The Case of Patients Treated with Acupuncture for Low Back Pain in a Traditional Chinese Medicine Clinic in China (and Story of a Bewildered Chicken).

Assessments of treatments for 'subjective symptoms' are problematic and potentially contentious. These are symptoms without ascertainable pathophysiology, also referred to as 'medically unexplained.' Treatments of them may be assessed from different perspectives, and an assessment as seen from one perspective may be discrepant with an assessment as seen from another perspective. The observational study described in the paper represents one perspective. Patients in the study were treated with acupuncture for the subjective symptom of low back pain in a Traditional Chinese Medicine Clinic in China; acupuncture is a form of TCM, which is indigenous to China. Shortly after treatment began and six months afterward, patients reported 'clinically important improvements' on a variety of standard, cross-culturally validated outcome measures, including pain intensity, physical functioning, and emotional functioning; this assessment is consistent with numerous assessments of acupuncture in China and other Southeastern Asian countries. On the other hand, clinical trials represent another perspective from which to assess acupuncture. Although assessments based on trials are not uniform, several assessments based on them, including those published in journals such as Lancet and New England Journal of Medicine, conclude that acupuncture is not effective. These trials, however, were mainly situated in the U.S., western European countries, and other WEIRD (Western, Educated, Industrialized, Rich, Democratic) countries. This is notable, because the population of China, the indigenous context of acupuncture, is greater than populations of WEIRD countries combined. Patients' expectations of a treatment such as acupuncture and their prior familiarity with it vary among contexts, and patients' experiences of treatment outcomes may vary accordingly. In short, although clinical trials constitute a test of truth in biomedicine and inform authoritative assessments in WEIRD countries, they do not necessarily represent the truth from the perspective of those experiencing outcomes of especially indigenous treatments for subjective symptoms in non-WEIRD contexts.

Si-Ni-San reduces lipid droplet deposition associated with decreased YAP1 in metabolic dysfunction–associated fatty liver disease

Ethnopharmacological relevanceMetabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. However, its complex pathogenesis and lack of effective drugs for treating it present significant challenges. Si-Ni-San (SNS) is one of the representative formulas for treating patients with MAFLD in traditional Chinese medicine (TCM) clinics. According to our previous work, SNS reduces lipid droplet (LD) deposition in livers of mice with MAFLD. Aim of the studyTo elucidate the mechanism of SNS in reducing LD deposition in MAFLD. Materials and methodsFirst, LD areas were detected with Oil red O staining in HepG2 cells induced by oleic acid (OA). Cell Counting Kit-8 (CCK-8) assay was used to test cell viability after treatment with different concentrations of SNS serum. The expression of Yes-associated protein 1 (YAP1) was monitored by Western blot. Second, C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and gavaged with SNS decoction during the 11th and 12th weeks. Then, the weight of the body and the liver was examined. LD numbers and their locations in the liver were detected by triglyceride (TG) assay and hematoxylin and eosin staining (H&E). The expression levels of YAP1 and perilipin2 (PLIN2) were detected using Western blot and immunohistochemistry (IHC) in liver tissues. Finally, active ingredients of SNS decoction and SNS serum were identified by liquid chromatography-mass spectrometry (LC-MS). Finally, molecular docking was performed between the compounds in SNS and YAP1 to analyze their active interaction. ResultsCellular experiments showed that SNS serum reduced LD vacuoles and YAP1 expression in OA-induced HepG2 cells. Animal experiments confirmed that LD vacuoles, PLIN2 expression (3.16-fold), and YAP1 expression (2.50-fold) were increased in the HFD group compared with the normal diet (ND) group. SNS reduced LD vacuoles, TG content (0.84-fold), PLIN2 expression (0.33-fold), and YAP1 expression (0.27-fold) compared with the normal saline (NS) group in Yap1Flox mice with MAFLD. In SNS, baicalein-6-glucuronide, desoxylimonin, galangin-7-glucoside, glycyrrhizic-acid, licoricesaponin-K2, and nobiletin showed a high binding effect with YAP1. Knockout of hepatocyte YAP1 reduced LD vacuoles, TG content (0.40-fold), and PLIN2 expression (0.62-fold) in mice. Meanwhile, SNS reduced LD vacuoles, TG content (0.70-fold), and PLIN2 expression (0.19-fold) in Yap1LKO mice with MAFLD. The effect of SNS in reducing TG and PLIN2 was diminished in Yap1LKO mice compared with Yap1Flox mice. ConclusionSNS reduced LD deposition and YAP1 expression in MAFLD liver cells both in vivo and in vitro. YAP1 was highly expressed in livers with MAFLD, and knockout of hepatocellular YAP1 reduced LD deposition in mice. SNS reduced LD deposition associated with decreased YAP1 in MAFLD liver cells.

CcTCM: A quantitative component and compound platform for promoting the research of traditional Chinese medicine

Traditional Chinese medicine (TCM) databases play a vital role in bridging the gap between TCM and modern medicine, as well as in promoting the popularity of TCM. Elucidating the bioactive ingredients of Chinese medicinal materials is key to TCM modernization and new drug discovery. However, one drawback of current TCM databases is the lack of quantitative data on the constituents of Chinese medicinal materials. Herein, we present ccTCM, a web-based platform designed to provide a component and compound-content-based resource on TCM and analysis services for medical experts. In terms of design features, ccTCM combines resource distribution, similarity analysis, and molecular-mechanism analysis to accelerate the discovery of bioactive ingredients in TCM. ccTCM contains 273 Chinese medicinal materials commonly used in clinical settings, covering 29 functional classifications. By searching and comparing, we finally adopted 2043 studies, from which we collected the compounds contained in each TCM with content greater than 0.001 %, and a total of 1449 were extracted. Subsequently, we collected 40,767 compound-target pairs by integrating multiple databases. Taken together, ccTCM is a versatile platform that can be used by TCM scientists to perform scientific and clinical TCM studies based on quantified ingredients of Chinese medicinal materials. ccTCM is freely accessible at http://www.cctcm.org.cn.