Herbal Textual Research on Farfarae Flos in Famous Classical Formulas / 中国实验方剂学杂志

By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.

Chiral separation methods and the applications in the study of chiral components of traditional Chinese medicines / 药学学报

Chirality is one of the fundamental properties of nature, and most of the important molecules in living organisms contain chiral structures. The efficacy and safety of drugs are often closely related to the chiral structure of compounds, however, there are relatively more studies on synthetic characterization, pharmacology, and toxicology of chiral small molecule chemical drugs, but relatively less studies on chiral compounds contained in natural drugs such as traditional Chinese medicines. Chiral separation, as the basis of chiral research, has a pivotal position in the study of chiral compounds. In this paper, we systematically describe the separation methods of chiral compounds from the classification of chiral splitting methods based on chromatographic and non-chromatographic methods, as well as chromatographic packing materials, chiral additives and chiral derivatization, and review the chiral compounds in natural drugs such as traditional Chinese medicines reported in the past ten years, in order to provide references for the splitting and evaluating the activity of chiral compounds, and the improvement of quality standards of traditional Chinese medicines.

Tiaoqi Jieyu acupuncture for treatment-resistant depression: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Tiaoqi Jieyu (regulating qi and relieving depression) acupuncture on the clinical symptoms of treatment-resistant depression (TRD), and to explore the relationship between the acupuncture pain sensitivity and symptom's improvement.@*METHODS@#A total of 78 patients with TRD were randomly divided into an observation group (39 cases, 3 cases dropped off) and a control group (39 cases, 4 cases dropped off). The patients in the control group were treated with medications according to the treatment plan of psychiatrists (at least one medication was 5-hydroxytryptamine reuptake inhibitor). On the basis of the control group, the patients in the observation group were treated with Tiaoqi Jieyu acupuncture, and Baihui (GV 20), Yintang (GV 24+), Yanglingquan (GB 34), Taichong (LR 3), Hegu (LI 4), Neiguan (PC 6), Yinlingquan (SP 9) and Zusanli (ST 36), etc. were selected. The acupuncture was given three times a week. Both groups were treated for 8 weeks. After 8-week treatment, the response rate of Hamilton depression scale-24 (HAMD-24) score after was evaluated in the two groups. The scores of HAMD-24 and Hamilton anxiety scale (HAMA) were compared between the two groups before treatment, after 4, 8-week treatment and 12 weeks after treatment (follow-up). After the first treatment and 8-week treatment, the visual analogue scale (VAS) score in the observation group was evaluated, and the correlation between VAS score after the first treatment and HAMD-24 score before treatment, between VAS score after the first treatment and the course of disease in the observation group was analyzed, and the correlation between difference of VAS after 8-week treatment and after the first treatment and difference of HAMD-24 score before treatment and after 8-week treatment was analyzed.@*RESULTS@#After 8-week treatment, the response rate of HAMD-24 score in the observation group was 52.8% (19/36), higher than 17.1% (6/35) in the control group (P<0.001). Compared before treatment, the scores of HAMD-24 and HAMA in the two groups were decreased after 4-week treatment, 8-week treatment and in follow-up (P<0.05), and those in the observation group were superior to the control group (P<0.05). After 8-week treatment, the acupuncture pain VAS score in the observation group was (5.28±2.13) points, which was higher than (3.33±1.62) points after the first treatment (P<0.001). There was a negative correlation between VAS score after the first treatment and HAMD-24 score before treatment in the observation group (r =-0.486, P=0.003); there was no correlation between acupuncture pain VAS score after the first treatment and the course of disease in the observation group (P>0.05). After 8-week treatment, there was a positive correlation between the difference of VAS score and the difference of HAMD-24 score in the observation group (r =0.514, P=0.001).@*CONCLUSION@#Tiaoqi Jieyu acupuncture could improve the depression and anxiety in patients with TRD, and the symptom's improvement is related to the recovery of acupuncture pain sensitivity.

Research progress on chemical constituents and pharmacological effects of Glechomae Herba and prediction of its Q-markers / 中国中药杂志

Glechomae Herba, the dried aerial part of Glechoma longituba(Labiatae), has the effects of promoting urination, draining dampness, and relieving stranguria. It has received wide attention in recent years owing to the satisfactory efficacy on lithiasis. Amid the in-depth chemical and pharmacological research, it has been found that Glechomae Herba has antibacterial, anti-inflammatory, antioxidant, antithrombotic, hepatoprotective, cholagogic, antitumor, hypoglycemic, and lipid-lowering effects. The main chemical constituents are volatile oils, flavonoids, terpenoids, phenylpropanoids, and organic acids. This paper summarized the chemical constituents and pharmacological effects of Glechomae Herba. Based on genetic relationship of plants, the characteristics, efficacy, and pharmacokinetics of the chemical constituents, and the potential of these constituents as quality markers(Q-markers), it was summed up that ursolic acid, caffeic acid, rosmarinic acid, luteolin-7-O-diglucuronide, apigenin, apigenin-7-O-diglucuronide, apigetrin, and glechone can be the candidate Q-markers of Glechomae Herba.

Research status of Bovis Calculus and relevant Chinese patent medicines based on bibliometric analysis / 中国中药杂志

With scarce resources, natural Bovis Calculus is expensive and hard to meet clinical demand. At the moment, four kinds of Bovis Calculus are available on the market: the natural product, in vitro cultured product, synthesized product, and the product formed in cow after manual intervention. In this study, papers on the four kinds of Bovis Calculus products and relevant Chinese patent medicines were searched from Web of Science, PubMed, and China National Knowledge Infrastructure(CNKI). CiteSpace, citexs AI, and CNKI were employed for bibliometric analysis and knowledge map analysis. On this basis, the status, trend, and focuses of research on Bovis Calculus and relevant Chinese patent medicines were summarized. The results suggested overall slow development in the research on Bovis Calculus and relevant Chinese patent medicines with three typical growth stages. It is consistent with the development of Bovis Calculus substitutes and the national policy for the development of traditional Chinese medicine. At the moment, the research on Bovis Calculus and relevant Chinese patent medicines has been on the rise. In recent years, there has been an explosion of research on them, particularly the quality control of Bovis Calculus and the Chinese patent medicines, the pharmacological efficacy of Chinese patent medicines, such as Angong Niuhuang Pills, and the comparison of the quality of various Bovis Calculus products. However, there is a paucity of research on the pharmacological efficacy and the mechanism of Bovis Calculus. This medicinal and the relevant Chinese patent medicines have been studied from diverse perspectives and China becomes outstanding in this research field. However, it is still necessary to reveal the chemical composition, pharmacological efficacy, and mechanism through multi-dimensional deep research.

Quality evaluation of Huocao based on UPLC fingerprint and multi-component content determination / 中国中药杂志

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.

Main components from cultivated and wild Nardostachyos Radix et Rhizoma by LC-MS and GC-MS / 中国中药杂志

In this study, ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography-mass spectrometry(GC-MS) were combined with non-targeted metabonomic analysis based on multivariate statistics analysis, and the content of five indicative components in nardosinone was determined and compared by UPLC. The main chemical components of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma were comprehensively analyzed. The results of multivariate statistical analysis based on liquid chromatography-mass spectrometry(LC-MS) and GC-MS were consistent. G1 and G2 of the imitative wild cultivation group and G8-G19 of the wild group were clustered into category 1, while G7 of the wild group and G3-G6 of the imitative wild cultivation group were clustered into category 2. After removing the outlier data of G1, G2, and G7, G3-G6 of the imitative wild cultivation group were clustered into one category, and G8-G19 of the wild group were clustered into the other category. Twenty-six chemical components were identified according to the positive and negative ion modes detected by LC-MS. The content of five indicative components(VIP>1.5) was determined using UPLC, revealing that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid C, linarin, nardosinone, and total content in the imitative wild cultivation group were 1.85, 1.52, 1.26, 0.90, 2.93, and 2.56 times those in the wild group, respectively. OPLS-DA based on GC-MS obtained 10 diffe-rential peaks. Among them, the relative content of α-humulene and aristolene in the imitative wild cultivation group were extremely significantly(P<0.01) and significantly(P<0.05) higher than that in the wild group, while the relative content of 7 components such as 5,6-epoxy-3-hydroxy-7-megastigmen-9-one, γ-eudesmol, and juniper camphor and 12-isopropyl-1,5,9-trimethyl-4,8,13-cyclotetrade-catriene-1,3-diol was extremely significantly(P<0.01) and significantly(P<0.05) lower than that in the wild group, respectively. Therefore, the main chemical components of the imitative wild cultivation group and wild group were basically the same. However, the content of non-volatile components in the imitative wild cultivation group was higher than that in the wild group, and the content of some volatile components was opposite. This study provides scientific data for the comprehensive evaluation of the quality of Nardostachyos Radix et Rhizoma with imitative wild cultivation and wild Nardostachyos Radix et Rhizoma.

Progress in research methods or strategies of compatibility mechanism of traditional Chinese medicine prescriptions / 中国药房

Compound formulas of traditional Chinese medicines （TCM）， also known as prescription in clinic， refers to a form of medication in which several TCMs are selectively combined according to the certain compatibility principles and the needs of patient’s condition， based on syndrome differentiation and treatment. At present， the methods and strategies for investigating the compatibility mechanisms of TCM prescriptions mainly focus on the following two aspects: analysis of pharmacological substances （including chemical composition analysis of TCM， ingredients of TCM analysis in blood， and pharmacokinetic analysis） and pharmacological signaling pathways analysis （involving network pharmacology analysis， signal pathway indicator detection， and metabolomics analysis）. In future research， the compatibility relationships of TCM prescriptions should be explored according to the principles of “Qiqing Hehe”，“ Shengjiang Fuchen”，“ Junchen Zuoshi”， and “Siqi Wuwei”. The regularity of TCM prescriptions compatibility should be shown in the change regularity of chemical components， pharmacokinetics， pharmacological pathways， and chemical compositions of various ratios of TCMs. Based on the insurance of holistic efficacy of TCM prescriptions， the underlying mechanisms of compatibility should be uncovered， which will provide references for the optimization of clinical applications of prescriptions and new directions for the creation of innovative TCM prescriptions.

Herbal Textual Research on Anemarrhenae Rhizoma in Famous Classical Formulas / 中国实验方剂学杂志

Through reviewing ancient and modern literature， the textual research of Anemarrhenae Rhizoma（AR） has been conducted to verify the name， origin， changes in production areas， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing AR. Through the herbal textual research， AR was first published in Shennong Bencaojing， and has been used as the proper name for this herb for generations， and the mainstream source of AR used for generations is the rhizome of Anemarrhena asphodeloides. The high-quality production areas that have been revered throughout the ages are Hebei， Shanxi， Shaanxi， Inner Mongolia and Fangshan district of Beijing， etc. In recent times， AR produced in Yixian county of Hebei province（Xiling Zhimu）， is better known and is regarded as a very good source. At present， cultivated AR is mainly produced in Yixian county and Anguo of Hebei province， Bozhou of Anhui province and other places. The medicinal parts of AR in ancient and modern times are all rhizomes， and the quality is better if it has thick flesh， hard wood， yellow outer color and white section color. The harvesting time recorded in ancient medical books is usually in lunar February and August， with exposure to dryness， while modern harvesting is spring and autumn. The processing methods of the past dynasties were mainly to remove the hair when using， avoid iron when cutting， process with wine or salt water， while the two main specifications in modern times are raw and salted products. Based on the systematic research， it is recommended that the dried rhizome of A. asphodeloides in the famous classical formulas be used for AR. If the original formula specifies processing requirements， it should be operated according to the requirements， if the processing requirements are not indicated， the raw products can be used as medicine.

Discussion on Development Status of Traditional Chinese Medicine Dispensing Granules and Survival Strategy of Enterprises / 中国实验方剂学杂志

As an important complementary form of decoction pieces of traditional Chinese medicine（TCM）， TCM dispensing granules has the advantages of being free of decoction， easy to take， easy to carry and easy to be dispensed， which greatly improves the capacity of emergency services of TCM and is more in line with the needs of modern society. With the end of the pilot project of TCM dispensing granules， the market has been fully liberalized， the competition has been intensified， and it is in the transition period of switching between the new standard and the old one， and there are some problems such as the shortage of varieties， the change of specifications and the difference of quality， and the production enterprises are facing new opportunities and challenges. Based on this， the authors intend to systematically sort out the policies and regulations， enterprise layout and standard formulation since the pilot of TCM dispensing granules. In view of the problems in the post-pilot stage and from the perspective of survival and development of enterprises， it is suggested that enterprises should establish a quality control system for the whole industry chain of TCM dispensing granules to reduce process costs and increase enterprise competitiveness， further increase the investment in scientific research， overcome the key technical problems of difficult varieties， actively and orderly promote the research of national standards， in order to ensure the integrity of clinical formula varieties， and establish and improve the efficacy evaluation mechanism of TCM dispensing granules， build a consistency evaluation system between TCM dispensing granules and decoction pieces. Government departments should strengthen the guidance， fully mobilize the enthusiasm of scientific research institutions， enterprises and hospitals， and explore the establishment of "government-industry-study-research-application" mode to promote the development of TCM dispensing granule industry.

Advances on toxicity and metabolism of alkaloids from the "toxic" traditional Chinese medicines / 药学学报

The "toxicity" and safety of traditional Chinese medicines have been seriously concerned. Alkaloids are the main pharmacodynamic components of many kinds of traditional Chinese medicines, which show strong biological activity at low concentration. It will also cause toxic side effects but if used improperly. Some alkaloids are both active and toxic, and the safety of related traditional Chinese medicines is particularly noteworthy. The efficacy or toxicity of alkaloids may be the result of the combined action of parent compounds and metabolites, which is not only related to the structural types of compounds, but also has obvious species differences between humans and animals. This review focused on the alkaloids contained in the "toxic" traditional Chinese medicines that are officially recorded in Chinese Pharmacopoeia and the metabolism patterns of alkaloids with different structures as well as the enzymes involved were summarized and discussed by referencing the publications in recent two decades. The present study will be beneficial to the rational use of these traditional Chinese medicines in clinic.

Fexaramine improves non-alcoholic fatty liver disease in mice by stimulating intestinal FXR / 药学学报

Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation of metabolic syndrome and has become one of the chronic diseases that endanger health around the world. There is still a lack of effective therapeutic drugs in clinical practice. Farnesoid X receptor (FXR) has been a popular target for NAFLD research in recent years. Fexaramine (Fex) is a potent and selective agonist of FXR, and its mechanism of action to improve NAFLD is unclear. Therefore, in this study, a mouse model of NAFLD was constructed using a high-fat, high-cholesterol diet and treated with Fex orally for 6 weeks. We evaluated the ameliorative effect of Fex on disorders of glucolipid metabolism in NAFLD mice, and preliminarily explored its potential mechanism of action. The animal experiments were approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM210913011). In this study, it was found that 100 mg·kg-1 Fex significantly inhibited body weight gain, alleviated insulin resistance, improved liver injury and lipid accumulation in NAFLD mice. The effect of Fex on the expression of hepatic intestinal FXR and its target genes in NAFLD mice was further examined. Analysis of serum and hepatic bile acid profiles and expression related to hepatic lipid metabolism. It was found that Fex could stimulate intestinal FXR, promote fibroblast growth factor 15 (FGF15) secretion, inhibit the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1), the rate-limiting enzyme of bile acid synthesis in liver, regulate bile acid synthesis by negative feedback, and improve the disorder of bile acid metabolism. At the same time, Fex reduces liver lipid synthesis and absorption, increases fatty acid oxidation, thus improving liver lipid metabolism. This study shows that Fex can improve NAFLD by activating intestinal FXR-FGF15 signal pathway and regulating liver lipid metabolism.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes.

OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes

SUMMARY OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Panax notoginseng saponins ameliorated LPS-induced acute lung injury in mice by inhibiting the activation of NF-κB / 药学学报

Acute lung injury (ALI) is a kind of lung disease mainly caused by excessive inflammatory reaction. At present, there is a lack of effective therapeutic drugs in clinic. The aim of this study was to investigate the improvement effect of Panax notoginseng saponins (PNS) on ALI and its potential mechanism. The model of wild-type C57BL/6J mice was established by intratracheal instillation of 50 μL 25 mg·mL-1 lipopolysaccharide (LPS). 24 h later, 200 and 400 mg·kg-1 PNS was given intragastric, respectively. 24 h after administration, the improvement effect of PNS on ALI mice was evaluated by lung function, wet-to-dry weight ratio (W/D), total protein, interleukin 6 (IL6) and tumor necrosis factor α (TNFα) concentration of bronchoalveolar lavage fluid (BALF), expression levels of IL6 and TNFα in lung tissues, pathological changes of lung tissues and expression of inflammatory cells in BALF. The protein expression levels of NF-κB and its upstream kinases in Raw264.7 cells and ALI mice lung tissues were further detected to evaluate the potential mechanism of PNS improving ALI mice. The experimental scheme was approved by the Animal Experiment Ethics Committee of Shanghai University of Traditional Chinese Medicine. It was found that 400 mg·kg-1 PNS could significantly improve the lung function of ALI mice, reduce the contents of W/D, BALF total protein, IL6 and TNFα, neutrophils expression in BALF and the infiltration of inflammatory cells in lung tissue. In Raw264.7 cells and ALI mice lung tissue, PNS significantly reduced the expression of NF-κB, reduced the protein expression and phosphorylation of NF-κB, promoted the expression of IκBα, and inhibited the inflammatory response. This study showed that PNS can improve ALI by inhibiting the activity of NF-κB, inhibiting the release of inflammatory factors and inflammatory cells infiltration, alleviating lung inflammation.

The protective effect of schisandrol A against senecionine-induced hepatotoxicity in mice / 药学学报

Hepatotoxicity induced by herbal medicines such as Gynura japonica, which contains large amount of pyrrolizidine alkaloids (PAs) such as senecionine (SEN), is among the most serious problems of herbal drug-induced liver injury, yet there is no effective treatment in clinic. We have previously reported that ritonavir (the well-known CYP3A4 inhibitor) protected rats against Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs. A large number of lignans have been identified in Schisandrae Chinensis Fructis and are reported to attenuate drug-induced liver injuries by modulating the drug metabolism enzymes. Therefore, the present study investigated the protective effect and potential mechanism of schisandrol A (SoA, a representative lignan identified in Schisandrae Chinensis Fructis) against SEN-induced hepatotoxicity in mice. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM210604002). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Liver injury was induced by a single gavage of SEN (150 μmol·kg-1); mice in the protection group were gavaged with SoA (116 μmol·kg-1) 7 days before SEN treatment. The results show that SoA dramatically alleviated SEN-induced liver injury in mice. Mice in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase; in addition, the hepatic necrosis and sinusoidal hemorrhage in SEN-treated mice were markedly attenuated in the protection group. The serum contents of SEN metabolites in mice were decreased. In vitro studies were performed by using human liver microsomes and proved that SoA inhibits CYP3A4 to decrease the metabolism of SEN. These studies indicate that SoA attenuated SEN-induced liver injury in mice, which was closely related to the inhibition of the metabolic activation of SEN. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work also will be helpful in developing effective treatments for SEN-induced liver injury based on inhibition of its metabolic activation, and in making reasonable evaluations of the safety of herbal medicines containing PAs such as G. japonica.

A Bibliometric Analysis and Visualization of Current Research Trends in Chinese Medicine for Osteosarcoma / 中国结合医学杂志

BACKGROUND@#To illustrate the research framework, overall knowledge structure, and development trends of Chinese medicine (CM) treatment for osteosarcoma (OS) by using a bibliometric analysis and newly developed visualization tools.@*METHODS@#Research datasets were acquired from the Web of Science (WOS) database from January 1, 1980 to September 30, 2019. VOS viewer and Citespace software was used to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution of institutes, distribution of journals, citation and H-index status, co-authorship status, research hotspots and co-citation status were analyzed.@*RESULTS@#A total of 223 publications in the WOS database met the requirement. The number of published articles showed a rise but the citation frequency and the H-index of China were relatively low. The cooperation between the countries, institutes and authors were relatively weak. Most publications were basic researches. Most of the previous researches focused on basic mechanisms of CM in treating OS, and therapy and improvement of dosage form may become a frontier in this research field.@*CONCLUSIONS@#Compared with other fields, the field of CM treatment for osteosarcome is still in infancy. The distribution of researches is imbalanced and cooperation between countries, institutions and authors remains to be strengthened. Furthermore, basic research occupies an absolute dominant position, and the exploration of the molecular mechanism of CM in preventing and treating OS may become a key point in the future.

Efficacy of postoperative radiotherapy based on modified clinical target volume according to high-frequency recurrence regions in patients with esophageal squamous cell carcinoma / 国际肿瘤学杂志

Objective:To analyze the survival efficacy, prognostic factors and failure patterns of patients with esophageal squamous cell carcinoma (ESCC) underwent postoperative radiotherapy (PORT) using modified clinical target volume (CTV) based on postoperative high-frequency recurrence regions, so as to provide reference for the further optimization of CTV of PORT.Methods:The patients with ESCC underwent radical operation in Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 28, 2014 to November 29, 2018 were retrospectively analyzed. Patients with stage pT 3-4aN 0 or N +, who underwent PORT with modified CTV based on postoperative high-frequency recurrence regions, were included in the study. Kaplan-Meier method was used to calculate overall survival (OS) and locoregional recurrence free survival (LRFS) , adverse events of patients were evaluated, Cox proportional hazards model was used for univariate and multivariate survival analysis, and the failure patterns of patients after PORT were analyzed. Results:A total of 85 patients were included in this study, and the median follow-up time was 52.6 months. The median OS of the whole group was 74.1 months. The 1-year, 2-year and 3-year OS rates were 97.6%, 84.7% and 71.7% respectively. The median LRFS was not reached, and the 1-year, 2-year and 3-year LRFS rates were 92.9%, 78.6% and 71.5% respectively. The incidence of grade 3-4 adverse events was 17.6% (15/85) , mainly including lymphopenia, bone marrow suppression, gastrointestinal reaction and skin reaction. Univariate analysis of OS after PORT showed that the degree of differentiation (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=4.19, 95% CI: 1.91-9.17, P<0.001; NA+basal-like group HR=4.16, 95% CI: 1.29-13.44, P=0.017) and postoperative stage ( HR=2.19, 95% CI: 1.09-4.39, P=0.030) were the influencing factors of OS. Cox multivariate analysis showed that the degree of differentiation was an independent prognostic factor for OS after PORT (set G1+G1-2+G2 group as the control group, G2-3+G3 group HR=5.24, 95% CI: 2.30-11.93, P<0.001; NA+basal-like group HR=4.83, 95% CI: 1.33-17.62, P=0.017) . The first failure patterns analysis showed that 39 cases (45.9%) had recurrence, among which, 22 cases (25.9%) had locoregional recurrence with the median onset time of 15.2 months after operation, 19 cases (22.4%) had distant metastasis with the median onset time was 14.1 months after operation, and 2 cases (2.4%) were mixed failure mode. Among the locoregional recurrence, 16 cases (72.7%) recurred in the radiation field. Among all the local recurrence sites, the lymph node drainage regions in the supraclavicular, upper middle mediastinum and upper abdominal perigastric/celiac artery trunk areas were the most common sites. Among the distant metastatic organs, lung, bone and liver metastases were the most common. Conclusion:Patients of ESCC with high risk of recurrence after radical esophagectomy have long survival time and high safety after PORT with modified CTV according to the high-frequency recurrence regions. It is worthy of further confirmation by multicenter, large sample and prospective clinical trials.

The protective effect of ritonavir against Gynura japonica-induced liver injury in rats / 药学学报

Numerous in vitro studies have shown that most pyrrolizidine alkaloids (PAs) are hepatotoxic after being metabolically activated by cytochrome P450 (CYP) 3A4. However, the key role of CYP3A4 has not been confirmed in vivo. Therefore, the CYP3A4 chemical inhibitor ritonavir was employed in this work and the effect of ritonavir on Gynura japonica-induced liver injury in rats was investigated. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Acute liver injury was induced by a single gavage of Gynura japonica extracts (GJE, 8 g·kg-1); rats in the protection group were gavaged with ritonavir (RIT, 30 mg·kg-1) 1 h before GJE treatment. The results show that RIT could significantly attenuate GJE-induced liver injury in rats. Rats in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase, as well as lower total bile acids. In addition, the infiltration of inflammatory cells, sinusoidal hemorrhage, and hepatic necrosis in GJE-treated rats were markedly attenuated in the protection group. The content of pyrrole-protein adducts (PPAs), a recommended biomarker for PA-induced hepatotoxicity in clinics, was determined at 10 min to 24 h after GJE treatment. The content of 13 bile acids was also quantified. RIT treatment reduced the content of PPAs in serum dramatically and restored the impaired bile acid homeostasis caused by GJE. These studies indicate that RIT attenuated Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs and the regulation of bile acid metabolism. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work will also be helpful in developing effective treatments for PA-induced liver injury and making a reasonable evaluation of the safety of drugs containing PAs in clinic.

Determination of six effective ingredients in Imperatae Rhizoma concentrated granules by ultra-performance liquid chromatography using two internal references / 药学学报

To simultaneously determine the contents of p-coumaric acid, chlorogenic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic acid and ferulic acid in Imperatae Rhizoma concentrated granules, an ultra-high performance liquid chromatography (UPLC) with two internal references method (TIRM) was established and validated. Chromatographic separation was achieved on a ZORBAX RRHD Eclipse Plus C18 column (2.1 mm × 100 mm, 1.8 µm) using 1.7 mmol·L-1 oxalic acid in water and methanol as mobile phase. The flow rate was 0.4 mL·min-1 and the column temperature was set as 35 ℃. The relative correction factors (RCFs) of caffeic acid and ferulic acid using p-coumaric acid as internal reference were calculated and the RCFs of 4-caffeoylquinic acid and 5-caffeoylquinic acid were calculated using chlorogenic acid as the internal reference. The TIRM was fully validated for linearity, accuracy, repeatability, stability and recovery so that it could be compared with the external standard method (ESM). The RCFs of 5-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic acid, and ferulic acid were 1.069, 1.022, 1.368, and 1.493, respectively. The TIRM and ESM were used to determine the contents of six ingredients in Imperatae Rhizoma concentrated granules from different manufacturers and the variation between results was within acceptable limits. In conclusion, the newly established TIRM allowed simultaneous determination of six ingredients (p-coumaric acid, chlorogenic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, caffeic acid, ferulic acid) in Imperatae Rhizoma concentrated granules, providing support for the quality control of this traditional Chinese medicine.