Humans ; Cyclosporine/therapeutic use* ; Anemia, Aplastic/drug therapy* ; Neoplasms/drug therapy* ; Immunosuppressive Agents/therapeutic use* ; Benzoates/therapeutic use*

Huocao(a traditional Chinese herbal medicine) moxibustion is a characteristic technology in Yi medicine suitable for cold-dampness diseases. Huocao, as the moxibustion material, is confusedly used in clinical practice and little is known about its quality control. In this study, UPLC method was used to establish the chemical fingerprint of non-volatile components in Huocao, and the contents of eight phenolic acids such as chlorogenic acid were determined. Multivariate statistical analysis was performed to obtain the indicator components of Huocao for quality evaluation, and thus a comprehensive evaluation system for the quality of Huocao was built. The UPLC fingerprints of 49 batches of Huocao were established, and there were 20 common peaks, of which eight phenolic acids including neochlorogenic acid and chlorogenic acid were identified. Except for three batches of Huocao, the similarity of the other 46 batches was higher than 0.89, suggesting that the established fingerprint method could be used for quality control of the medicinal herb. The correlation coefficient between entropy weight score of the eight phenolic acids and comprehensive fingerprint score in Huocao was 0.875(P<0.01), which indicated that the eight phenolic acids could be used as indicator components for the quality evaluation of Huocao. Furthermore, in multivariate statistical analysis on the common peaks of fingerprint and the contents of the eight phenolic acids, chlorogenic acid, isochlorogenic acid A and isochlorogenic acid C were screened to be the indicator components. The results revealed that the proposed method achieved a simple and accurate quality control of Huocao based on UPLC fingerprint and multi-component content determination, which provided useful data for establishing the quality standard of Huocao.
Chlorogenic Acid ; Entropy ; Hydroxybenzoates ; Quality Control

Objective: To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods: Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results: Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion: Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.
Male ; Humans ; Adult ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Purpura, Thrombocytopenic, Idiopathic/diagnosis* ; Retrospective Studies ; Treatment Outcome ; China/epidemiology* ; Benzoates/therapeutic use*

Moutan Cortex(MC) residues produced after the extraction of MC can be re-extracted for active components and used to produce organic fertilizer and animal feed. However, they are currently disposed as domestic waste, which pollutes the environment. This study analyzed the chemical composition of the medicinal material, residues, and residue compost of MC by UPLC-UV-Q-TOF-MS. Furthermore, the nutrient composition of MC residues and the residue compost was analyzed. The results showed that:(1)MC residues had lower content of chemicals than the medicinal material, and content of paeonol, gallic acid, and galloylglucose in MC residues were about 1/3 of that in the medicinal material. The content of chemicals were further reduced after residue composting, and the quantitative compounds were all below the limits of detection.(2)Compared with MC residues, the residue compost showed the total nitrogen, total phosphorus, total potassium, and organic matter content increasing by 122.67%, 31.32%, 120.39%, and 32.06%, respectively. Therefore, we concluded that the MC residues can be used to re-extract active compounds such as paeonol, gallic acid, and galloylglucose. The MC residue compost is a high-quality organic fertilizer containing minimal content of chemicals and can be widely used in the cultivation of Chinese medicinal herbs.
Animals ; Composting ; Fertilizers ; Soil/chemistry* ; Hydrolyzable Tannins ; Nutrients ; Acetophenones ; Drugs, Chinese Herbal ; Paeonia

BACKGROUND: Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. METHODS: This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. RESULTS: At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. CONCLUSIONS: Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. REGISTRATION ClinicalTrials.gov, NCT04214951.
Adult ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; Thrombopoietin/adverse effects* ; Prospective Studies ; Recombinant Fusion Proteins ; Receptors, Fc/therapeutic use* ; Receptors, Thrombopoietin/therapeutic use* ; Thrombocytopenia/chemically induced* ; Benzoates/adverse effects* ; Hydrazines/adverse effects*

Dao-di herbs, produced in a specific region and screened through long-term clinical application, is characterized by high stable quality, good efficacy, and high popularity. With favorable climate conditions, Gansu gives birth to the Dao-di herbs Angelicae Sinensis Radix which is widely used in clinical practice, and multiple regions in Gansu, with similar ecological environment produce Angelicae Sinensis Radix. In this study, the spatial correlation and difference of phenolic acid content in Angelicae Sinensis Radix from Dao-di producing areas, emerging producing areas, and emerging planting areas in Gansu were analyzed based on ArcGIS to explore the "quality(chemical type)" characteristics of genuine Angelicae Sinensis Radix. Moreover, spatial distribution law and main driving factors of the total phenolic acid content in Angelicae Sinensis Radix in Gansu were analyzed based on geodetecctor. This study is expected to lay a basis for Dao-di research and production regionalization of Angelicae Sinensis Radix.
Angelica sinensis ; Cell Differentiation ; Drugs, Chinese Herbal ; Hydroxybenzoates

In this paper, the newly isolated tannins were sorted after a review of the literature concerning tannins in recent 10 years, and their research progress was summarized in terms of extraction, isolation, pharmacological activity and metabolism. Hydrolysable tannins and condensed tannins are the main structural types. Modern research shows that tannins have many pharmacological effects, such as bacteriostasis, antioxidation, antitumor, antivirus and blood glucose reduction, and have broad development prospects. They are usually extracted by water, ethanol and acetone and isolated and purified by macroporous resin and gel column chromatography. The packings commonly adopted for the column chromatography mainly included Sephadex LH-20, Diaion HP-20, MCI-gel CHP-20 and Toyopearl HW-40. Modern analytical techniques such as nuclear magnetic resonance spectroscopy(NMR), fast atom bombardment mass spectrometry(FAB-MS) and circular dichroism(CD) are generally used for the structural identification of tannins. Howe-ver, their isolation, purification and structural identification are still challenging. It is necessary to use a variety of high-throughput screening methods to explore their pharmacological activities and to explore the material basis responsible for their functions through experiments in vivo.
China ; Hydrolyzable Tannins ; Medicine, Chinese Traditional ; Proanthocyanidins ; Tannins

A new phenolic acid ester, 4'-hydroxyphenylethyl 4,8(R)-dihydroxyphenylpropionate(1), was isolated from an endophytic fungus Colletotrichum capsici of Paeonia lactiflora roots, along with eight known phenolic derivatives, tyrosol(2), 2-(4-hydroxyphenyl) ethyl acetate(3), methyl p-hydroxyphenylacetate(4), methyl m-hydroxyphenylacetate(5), 4-(4-hydroxyphene-thoxy)-4-oxobutanoic acid(6), 4-hydroxyphenethyl methyl succinate(7), trichodenol B(8) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl) acetate(9). Their structures were identified by a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) spectroscopy, ultraviolet(UV) spectroscopy and electronic circular dichroism(ECD) spectroscopy. Compounds 2-9 were isolated from this fungus for the first time.
Colletotrichum ; Esters ; Hydroxybenzoates ; Paeonia

There is no consensus on the content, accumulation, transformation and content determination methods of phenolic acids in fresh Salvia miltiorrhiza. In order to find out the true content of phenolic acids in fresh S. miltiorrhiza, a variety of treatment me-thods were used in this study to prepare sample solution. The content changes of phenolic acids in S. miltiorrhiza samples with different dehydration rates were investigated during drying and shade drying processes. Polyphenol oxidase(PPO) of S. miltiorrhiza was extracted and purified by ammonium sulfate precipitation and dialysis to investigate the enzymatic properties. The content of rosmarinic acid, lithosperic acid and S. nolic acid B in S. miltiorrhiza was determined by UPLC. The results showed that the content of phenolic acids in fresh S. miltiorrhiza was highest when it was homogenized with 1 mol·L~(-1) HCl solution or 1 mol·L~(-1) HCl methanol solution. There was no significant difference in the content of phenolic acids in S. miltiorrhiza with different dehydration rates, indicating that there was no correlation between phenolic acid content and dehydration rate. The optimum pH of S. miltiorrhiza PPO was 7.6 and the optimum temperature was 40 ℃. With catechol as substrate, S. miltiorrhiza PPO had the enzymatic browning reaction which was in compliance with Michaelis equation, with Michaelis constant K_m of 0.12 mol·L~(-1) and V_(max) of 588.23 U·min~(-1). The inhibitory effect of citric acid, disodium ethylenediamine tetraacetate, ascorbic acid and sodium sulfite on S. miltiorrhiza PPO increased with the increase of inhibitor concentration, and sodium sulfite showed the strongest inhibitory effect. The present study proved that there were a large number of phenolic acids in fresh S. miltiorrhiza, which were the secondary metabolite of primitive accumulation during the growth of S. miltiorrhiza, rather than the induced product of postharvest drying and dehydration stress. This study has reference value and significance for the cultivation, harvest and processing of S. miltiorrhiza.
Catechol Oxidase ; Desiccation ; Hydroxybenzoates ; Plant Roots ; Salvia miltiorrhiza

Objective To study the changes of metabolites in serum and tissues （kidney, liver and heart） of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Orbitrap HRMS）. Multivariate statistical principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.
Animals ; Biomarkers/metabolism* ; Chromatography, High Pressure Liquid ; Mass Spectrometry ; Metabolome ; Metabolomics ; Mice ; Mice, Inbred ICR ; Tetracaine