Rapid screening of 28 alkaloids in food poisoning samples by liquid chromatography-tandem mass spectrometry / 中国热带医学

@#Abstract: Objective　To investigate a poisoning incident caused by eating eight treasure congee, and establish liquid chromatography (LC)-mass spectrometry (MS)/MS screening method of 28 alkaloids to provide references for disposal of similar poisoning incidents. Methods　LC-MS/MS was used for screening 28 alkaloids in the urine, eight treasure congee and food raw material, and the detected alkaloids were quantified. Samples were extracted with 0.4% formic acid aqueous solution and separated by a Acquity UPLC BEH C18 column (1.7 μm, 100 × 2.1 mm). Acetonitrile-0.2% formic acid aqueous solution was used as the mobile phase and gradient elution was adopted. The ionization mode was electrospray positive ionization mode, and the detection method was multi-reaction monitoring (MRM). Analytes were quantified with the external standard method. Results　In the concentration range of 0-100 ng/mL, the linear correlation coefficient r were greater than 0.999 for 28 alkaloids. The recovery of 28 alkaloids in urine sample ranged from 63.0% to 105.0%, and the relative standard deviations (RSDs) were between 5.8% and 8.6%. The recovery of 28 alkaloids in eight treasure congee sample ranged from 72.0% to 109.0%, and the RSDs were between 6.3% and 9.7%. The recovery of 28 alkaloids in semen sesami nigrum sample ranged from 60.0% to 95.0%, and the RSDs were between 4.8% and 8.2%. Hyoscyamine (2 380.0 ng/mL), scopliamine (3.6 ng/mL) and rac-anisodamine (4.7 ng/mL) were detected in the patient's urine. Hyoscyamine (63.3 μg/g), scopliamine (5.7 μg/g) and rac-anisodamine (2.1 μg/g) were detected in eight treasure congee. Hyoscyamine (901.0 μg/g), scopliamine (80.0 μg/g) and rac-anisodamine (30.1 μg/g) were detected in the seed of Datura stramonium L. The ratio of scopliamine and hyoscyamine in the seed of D. stramonium was 1∶11, which complies with the characteristics of D. stramonium L. In urine sample, the proportion of scopliamine and rac-anisodamine was 0.15% and 0.20%, and hyoscyamine accounted for 99.65%. Conclusion　Seed morphology, the content range and proportion of three alkaloids are all in accord with the characteristics of D. stramonium. Combined with the clinical symptoms of atropine poisoning, it can be deduced that this incident is a family food poisoning caused by accidental consumption of seed of D. stramonium L. The method can provide technical support for the clinical diagnosis and treatment of alkaloid poisoning patients, and also provide a basis for emergency detection and disposal of alkaloid poisoning events.

Research progress on medical image dataset expansion methods / 生物医学工程学杂志

Computer-aided diagnosis (CAD) systems play a very important role in modern medical diagnosis and treatment systems, but their performance is limited by training samples. However, the training samples are affected by factors such as imaging cost, labeling cost and involving patient privacy, resulting in insufficient diversity of training images and difficulty in data obtaining. Therefore, how to efficiently and cost-effectively augment existing medical image datasets has become a research hotspot. In this paper, the research progress on medical image dataset expansion methods is reviewed based on relevant literatures at home and abroad. First, the expansion methods based on geometric transformation and generative adversarial networks are compared and analyzed, and then improvement of the augmentation methods based on generative adversarial networks are emphasized. Finally, some urgent problems in the field of medical image dataset expansion are discussed and the future development trend is prospected.

A survey of loss function of medical image segmentation algorithms / 生物医学工程学杂志

Medical image segmentation based on deep learning has become a powerful tool in the field of medical image processing. Due to the special nature of medical images, image segmentation algorithms based on deep learning face problems such as sample imbalance, edge blur, false positive, false negative, etc. In view of these problems, researchers mostly improve the network structure, but rarely improve from the unstructured aspect. The loss function is an important part of the segmentation method based on deep learning. The improvement of the loss function can improve the segmentation effect of the network from the root, and the loss function is independent of the network structure, which can be used in various network models and segmentation tasks in plug and play. Starting from the difficulties in medical image segmentation, this paper first introduces the loss function and improvement strategies to solve the problems of sample imbalance, edge blur, false positive and false negative. Then the difficulties encountered in the improvement of the current loss function are analyzed. Finally, the future research directions are prospected. This paper provides a reference for the reasonable selection, improvement or innovation of loss function, and guides the direction for the follow-up research of loss function.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations / 药物分析学报

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Textual Research on Ancient and Modern Literature of Classical Prescription Wandaitang / 中国实验方剂学杂志

The Wandaitang，recorded in an ancient medical book named Fu Qingzhu's Obstetrics and Gynecology，is one of the Classical Prescriptions. The detailed discussion and record on Wantaitang by later medical scholars can be also regarded as the inheritance and development of the original academic thought from Fu Qingzhu's Obstetrics and Gynecology. By referring to recent literatures，we have found that there are a few reports on Wandaitang from the perspective of ancient literature，but such reports are not systematic or comprehensive enough. Under the premise of inheriting but not rigidly adhering to the ancients，investigation and analysis would be made in this paper from the aspects of the origin，efficacy，dose conversion between ancient and modern uses，usage and dosage form，modern clinical application，contraindications and others based on ancient and modern literatures，in order to further promote the textual research work on Wandaitang and provide reference for its secondary research and development. The research results showed that the origin of Wandaitang can be traced back to the Bianzhenglu（Collecting Record of Differentiation of Symptoms and Signs），and its effect can be summarized as invigorating Qi and spleen，soothing liver-Qi stagnation，elevating yang and arresting leucorrhoea. In view of the great difference between the dose of the original prescription of Wandaitang and the recommended dose in the pharmacopoeia，the author recommended that the clinical dosage of Wandaitang should be 30 g Atractylodis Macrocephalae Rhizoma，30 g Dioscoreae Rhizoma，6 g Ginseng Radix et Rhizoma，15 g Paeoniae Radix Alba，10 g Plantaginis Semen，10 g Atractylodis Rhizoma，3 g Glycyrrhizae Radix et Rhizoma，3 g Citri Reticulatae Pericarpium，3 g Schizonepetae Spica Carbonisata，and 3 g Bupleuri Radix. The main indications included leucorrhea，vulva pruritus，diarrhea，stranguria，anorexia，eczema，vertigo and so on. This prescription should be used with caution in pregnant women or those with excessive phlegm and dampness，Qi stagnation of spleen and stomach，or deficiency of Yin-fluid and blood. The research and development of Wandaitang compound preparation can be inclined to the direction of compound granules，to give full play to its clinical value and market value. The above studies，based on the textual research of ancient and modern literatures，are of great significance for clarifying the origin and clinical application of Wandaitang，and provide a new idea and basis for the secondary development of Wandaitang.

Efficacy of Chinese Medicinal Formulae for Antimicrobial-resistant Pneumonia: A Systematic Review and Meta-analysis / 中国实验方剂学杂志

Objective:To evaluate the efficacy and safety of Chinese medicinal formulae in the treatment of antimicrobial-resistant pneumonia. Method:Following article retrieval from eight databases and data extraction by two reviewers， the methodological quality of the included trials was assessed and the outcome indicators were subjected to Meta-analysis using RevMan 5.3. Result:A total of 24 randomized controlled trials （RCTs） were included， involving 1 818 cases. Meta-analysis showed that Chinese medicinal formulae combined with western routine intervention was superior to the western routine intervention in improving the overall response rate （ORR） ［relative risk （RR）=1.27， 95% confidence interval （CI） （1.21， 1.34）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M005.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M005c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］， the bacterial clearance rate ［RR=1.49，95% CI （1.33， 1.66）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M006.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M006c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］， and the clinical pulmonary infection score （CPIS） ［mean difference （MD）=-1.64， 95% CI （-1.87， -1.41）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M007.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M007c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］. There was no significant difference in the incidence of adverse reactions ［RR=0.72， 95% CI （0.48， 1.07），<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mtext> </mml:mtext><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M008.jpg"><?fx-imagestate width="3.04799986" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M008c.jpg"><?fx-imagestate width="3.04799986" height="2.62466669"?></graphic></alternatives></inline-formula>=0.1］. The comparison with the western routine intervention also revealed that Chinese medicinal formulae better improved the ORR and CPIS. Conclusion:According to the current research results， the Chinese medicinal formulae alone or combined with western routine intervention yielded more favorable clinical outcomes than western routine intervention in the treatment of antimicrobial-resistant pneumonia， without increasing the incidence of adverse events. Due to limited quality and quantity of the included RCTs， more high-quality trials are required to verify the above conclusions.

Textual Research on Ancient Literature of Classical Prescription Kaixinsan and Its Associated Prescription / 中国实验方剂学杂志

The classical prescription Kaixinsan，which is recorded in an ancient medical book named Beiji Qianjin Yaofang，is one of the famous prescriptions used by ancient physicians to treat amnesia. Research on classical prescriptions has attracted more and more attention from scientific research institutions and related enterprises. Based on ancient books，textual research on origins and development of prescriptions，combing the evolution of prescriptions，preparations，oral ways，taboos and others are the important contents of the study on classical prescriptions. The research results show that the creation of Kaixinsan in Beiji Qianjin Yaofang can be traced back to Kaixinsan recorded in Jiyanfang and Dingzhiwan recorded in Gujinluyanfang. Later generations of physicians created many associated prescriptions in the process of applying Kaixinsan，and the efficacy of these prescriptions was constantly expanded with the development of the times. In the Tang and Song dynasties，Kaixinsan and its associated prescriptions were mainly used to treat amnesia，sorrow，fear，and other diseases. In the Jin and Yuan dynasties，these prescriptions were also used to treat convulsions and yawning. In the Ming dynasty， they were mainly for the treatment of hyperopia， myopia， sprematorrhea，and constipation. In the Qing dynasty，these herbs could be used to treat auricular deafness， aging and sweating. The dosage of Ginseng Radix et Rhizoma and Poria should be increased in the treatment of farsightedness，spermatorrhea and blurred urine，and in the treatment of nearsightedness，the dosage of Polygalae Radix and Haliotidis Concha should be increased. The main pathogenesis of the disease that Kaixinsan and its associated prescriptions treated could be summarized as the deficiency of heart and spleen，imbalance between heart-Yang and kidney-Yin，and the internal resistance of phlegm stagnation. By summarizing the contents of the preparation of tradition Chinese medicine products for Kaixinsan and its associated prescriptions，it is suggested that the dosage form of Kaixinsan can be pills，with the specification size confroming to the most record of ancient generations of physicians，as big as Firmiana platanifolia's fruit.The volume of a single pill is about 0.25 mL and the weight is about 0.3 g. The initial dosage is fifteen pills，which can be modified according to the severity of the illness，with no more than forty pills for each time，three times a day. Also，some excitant food like the sour food，sweet food and mutton should be avoided during the medication. The above research results can provide literature basis for the development of compound tradition Chinese Medicine preparation of Kaixinsan.

Textual Research on Ancient and Modern Literature Analysis and Research of Classical Prescriptions for Shentong Zhuyutang / 中国实验方剂学杂志

The Shentong Zhuyutang is recorded in an ancient medical book named Yilin Gaicuo， and it is one of the classical prescriptions. Based on the literature reviewed，it is generally found that the Shentong Zhuyutang is evolved from the prescription named Chentongsan that recorded by Danxi Xinfa. Statistics on the dosage of clinical research on this prescription in recent years， reference to the textbook and pharmacopoeia dose， at the same time to respect the original dosage， verify historical changes， and ensure the safety of prescriptions， at the same time consider the pharmacy's dispenses， the author recommends that the clinical dosage of Shentong Zhuyutang could be 3 gram of Gentianae Macrophyllae Radix， 6 gram of Chuanxiong Rhizoma， 10 gram of Persicae Semen， 10 gram of Carthami Flos， 6 gram of Glycyrrhizae Radix Et Rhizoma， 3 gram of Notopterygii Rhizoma Et Radix， 5 gram of Myrrha， 12 gram of Angelicae Sinensis Radix， 5 gram of Cyperi Rhizoma，12 gram of Cyathulae Radix， and 6 gram of Pheretima used as a reference. The efficacy of the compound preparation can be marked as promoting blood circulation， removing blood stasis， removing wind and dampness， and relieving pain. At present， most of its research is focused on clinical research and experimental research， and there are few literature on the research of Shentong Zhuyutang from the level of key information verification. The diseases it treats include more than 10， such as Gubi， Pibi， Xuebi， shechuanchuan， headache， postpartum pain and dysmenorrhea， especially in the study of Gubi， which means that it has a huge market demand and broad development prospects in orthopedic diseases， the core point of "blood stasis and cold dampness evil" should be closely held in the course of treatment. Some scholars deem that Shentong Zhuyutang should not be used the method of Force Sweat in the treatment of Bizheng，while others believe that this prescription should be used with caution in menstruation， pregnancy and blood deficiency. Modern pharmacological studies have shown that Shentong Zhuyutang has obvious anti-inflammatory， relieve pain， anticoagulan， nerve and bone protection. In view of the fact that there are less researches on Shentong Zhuyutang except for Gubi， this suggests that the mechanism of this prescription treat other diseases has a relatively broad research space.

Textual Research of Persicae Semen / 中国实验方剂学杂志

Textual research on Chinese herbs is the preliminary work for the preparation of famous classical prescriptions. Through literature review，it was found that the researches of Persicae Semen focused on chemical compositions，pharmacological mechanism and medical record analysis in the recent years，and few researches based on the ancient literature were about the origin，concocting methods，flavor，meridian tropism，effects and indications. Textual research shows that the most commonly used names are Taoren and Taoheren，with a wide range of producing areas. The plant origin of Persicae Semen has not changed much since ancient times. Before the Qing dynasty，the plant origin of Persicae Semen was from the seeds of a kind of fruit named Shantao or Maotao，and in modern times，the seeds of Amygdalus persica or A. davidiana have become the major source. While different books have different views on Latin names for the origin of the Persicae Semen. We suggest that the Latin names of A. persica and A. davidiana should be more reasonable for Tao and Shantao respectively .In the concocting methods of Persicae Semen for activating vital energy and blood circulation，raw Persicae Semen should be used with peel and tip，while for moisturizing dryness，it should be fried into yellow without peel. Therefore，in the concocting methods of Persicae Semen for Taohe Chengqitang and Taohong Siwutang，the raw materials should be fried into yellow without peel or tip，while for Shentong Zhuyutang，raw Persicae Semen materials should be used with peel and tip. The indications of Persicae Semen include amenorrhea，lump，parasite，obstruction of chest，cough and asthma，constipation，etc.，and the people with blood deficiency，blood dryness and the pregnant women should use it with caution or should not use it. The modern clinical application of Persicae Semen is only a partial inheritance of ancient literature，which means that the Persicae Semen still has many effects to be verified and studied，and it is worthwhile for further exploration in order to expand its clinical application. The records of ancient literature on flavor，meridian tropism，and quality evaluation of Persicae Semen were consistent with those in Chinese Pharmacopoeia. Because of the similar appearance，it is especially difficult to distinguish Persicae Semen and Armeniacae Semenis Amarum after crushing ，requiring much time and money for identification. It is recommended that medical institutions should purchase Persicae Semen without crushing as far as possible，then decide the best concocting methods according to the clinical requirement.

Correlation Between Intestinal Flora and Traditional Chinese Medicine Syndromes of Diarrhea： A Review / 中国实验方剂学杂志

Diarrhea is characterized by increased bowel movements and loose and even watery stools. Its occurrence and development have been proved by modern research to be closely related to the imbalance of intestinal flora. Traditional Chinese medicine （TCM） pays a special attention to syndrome differentiation in treating diarrhea. Exploring the TCM syndromes of diarrhea is of great significance to the formulation of TCM diagnosis and treatment scheme of diarrhea and the improvement of clinical curative effects. There exist many similarities between TCM theory and micro-ecological theory concerning diarrhea. With the deepening of intestinal flora research， the significance of intestinal flora in TCM syndrome research has been increasingly highlighted. The close correlation of intestinal flora with the occurrence and development of diarrhea has provided new ideas of deducing syndrome and selecting prescription based on intestinal flora. This paper summarized the relationship between TCM syndromes of diarrhea and microscopic indexes such as immune response， neurotransmitters， brain-gut peptide， and proteins and analyzed the intestinal flora characteristics related to six common TCM syndromes of diarrhea. Meanwhile， based on the theory of deducing syndrome by prescription， namely deducing the syndrome by the efficacy of prescription or its medicinal components， the correlation between TCM syndromes of diarrhea and intestinal flora was indirectly verified， so as to identify the research direction of correlation between intestinal flora and TCM syndromes in the future. Numerous studies have shown that the TCM syndromes of diarrhea were highly correlated with the microscopic indexes such as inflammatory cytokines， neurotransmitters， and proteins. Syndromes and dysbacteriosis both resulted from pathogenic factors acting on the body， which were summarized from different angles. Different TCM syndromes corresponded to specific objective indicators of intestinal flora. Intestinal flora has the potential of being an internal material basis for powerfully revealing the TCM syndromes of diarrhea in the future.

Relation Textual Research Between Effect Variation and Dosage of Famous Classical Formula Kaixinsan / 中国实验方剂学杂志

Kaixinsan recorded in an ancient medical book named Beiji Qianjin Yaofang is one of the famous classical formula，which is one of the common prescriptions used by ancient physicians to treat amnesia. In the process of using this prescription，later generations of physicians derived many kinds of associated prescriptions. The effect and indications of these prescription have been inherited and expanded from those in the Beiji Qianjin Yaofang because of the changes in dosages. Therefore，it is necessary to verify the effect and indications of the formulas and the rules of dosage changes. The research results showed that its basic effects included to nourish the mind，induce resuscitation，strengthen the spleen and calm the mind，and keep balance between heart-Yang and kidney-Yin. The main indications included amnesia，sorrow and sadness，fright and fear，and so on，which may differ slightly in different dynasties. In Song，Jin and Yuan dynasties，it also demonstrated the effect of warming the heart and Yang，clearing away heat and relieving wind besides the basic effects， with basically the same indications （slightly different from those in previous dynasties）. In Ming dynasty，it demonstrated the effect of nourishing Yin，clearing away heat and nourishing blood besides the basic effects，and the indications expanded to farsightedness，nearsightedness，spermatorrhea and blurred urine. In the Qing dynasty，its effect also included to nourish the heart and kidney on the basis of the Ming dynasty，and the indications were basically the same with those in the previous dynasties. The compatibility ratio of ancient physicians in the application of this prescription and its associated prescriptions showed some remarkable features，for example，Ginseng Radix et Rhizoma and Poria should be increased and their ratio was≈1∶1 in the treatment of amnesia，sorrow，sadness，fright，fear，farsightedness，spermatorrhea and blurred urine，with ratio of Polygalae Radix to Acori Tatarinowii Rhizoma≈1∶1； the dosage of Polygalae Radix and Acori Tatarinowii Rhizoma should be increased in the treatment of nearsightedness，and their ratio was≈1∶1. The compatibility ratio of Polygalae Radix-Ginseng Radix et Rhizoma-Poria-Acori Tatarinowii Rhizoma=2∶3∶3∶2 was the most frequent，which basically included the indications of this prescription and its associated prescriptions. According to statistics，the average dosages that ancient physicians used were significantly higher than those in the modern times，Polygalae Radix 57 g，Ginseng Radix et Rhizoma 62 g，Poria 70 g，and Acori Tatarinowii Rhizoma 54 g，respectively in ancient times，while Polygalae Radix 11 g，Ginseng Radix et Rhizoma 15 g，Poria 17 g，and Acori Tatarinowii Rhizoma 9.5 g，respectively in modern times. The above textual research results can provide some reference for preparation of tradition Chinese medicine products of Kaixinsan.

Literature Research on Origin and Application of Classical Prescription Xiebaisan / 中国实验方剂学杂志

Xiebaisan is one of the 100 classical prescriptions published by the state， and the research and development of its compound preparation has gradually become an upsurge. The research and development of classical prescriptions should start from the theory of traditional Chinese medicine and clinical practice， laying a solid foundation for research and development. Based on the above thinking， this study adopts the methods of traceability and bibliometrics to analyze the source， pathogenesis， efficacy， Fangyi and clinical application of Xiebaisan in order to further promote its literature research work. The results show that the origin of Xiebaisan can be traced back to the prescription of Xiefeitang in Yinhai Jingwei（Volume 1）. Although there are more than 20 prescriptions with the same name of Xiebaisan developed in later generations， they either reflect the inheritance and development of Qian Yi's thought of composing prescriptions， or only the meaning of "Xiebai" in the name of the prescription. The main pathogenesis of Xiebaisan is adverse lung Qi of heat. Mori Cortex and Lycii Cortex are sweet and cold， which can clear away lung heat and reduce adverse Qi， and then cough and asthma can stop. Supplemented with Glycyrrhizae Radix et Rhizoma and japonica rice， which are endowed with the meaning of nourishing earth and generating gold， to invigorate spleen and replenish Qi. The compatibility of Xiebaisan can clear away lung heat， relieve cough and asthma， and norish erath and generate gold to treat lung heat， asthma and cough. Although the main treatment of Xiebaisan recorded in ancient books involves various diseases and syndromes of internal， external， gynecology and pediatrics， the pathogenesis of Xiebaisan is "adverse lung Qi of heat". Modern clinical application of Xiebaisan focuses on the respiratory system， skin and subcutaneous tissue system， ear， nose and throat system， digestive system， ophthalmic system， etc.， and it has more advantages in the treatment of pneumonia， cough， bronchitis， epistaxis， acne， bronchiectasis， postinfectious cough， constipation and other diseases. The syndrome differentiation of the above diseases is in accordance with the relevant syndrome types with lung heat as the main pathological factor， so we can modify and apply the prescription appropriately.

Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology / 中国天然药物

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.

Mechanism and experimental verification of Sijunzi Decoction in treatment of ulcerative colitis based on network pharmacology / 中国中药杂志

To explore the mechanism of Sijunzi Decoction in the treatment of ulcerative colitis(UC) based on network pharmacology. The active components and corresponding targets of Sijunzi Decoction were extracted with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets were standardized with the help of Uniprot database. The related targets of UC were obtained through GeneCards database and Disgenet database, and the intersection targets of drugs and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein-protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology(GO) and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG) pathway were carried out on Bioconductor platform, and some of the targets were verified by animal experiments. Through database analysis, a total of 135 active components of Sijunzi Decoction, 114 predicted targets and 80 common targets with UC were obtained. The core target proteins included interleukin 6(IL-6), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR) and so on. GO functional enrichment analysis involved 102 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis showed that 120 items were involved in human cytomegalovirus infection, cancer, apoptosis, inflammation and other pathways. Mouse experiments showed that Sijunzi Decoction could down-regulate the expression of target proteins IL-6 and caspase-3 and inhibit intestinal epithelial cell apoptosis. The treatment of UC with Sijunzi Decoction is the result of the interaction among multi-components, multi-targets and multi-pathways. It is proved by experiments that Sijunzi Decoction may play an effective role by regulating the expression of IL-6 and caspase-3, and getting involved in apoptosis, inflammation and other pathways.

Effect of High Dose Vitamin C on Proliferation and Apoptosis of Acute Myeloid Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34 leukemia cells in AML.@*METHODS@#CD34 cells were sorted by using immunomagnetic cell sorting system, then the primary CD34 leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot.@*RESULTS@#The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34 leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34 cells.@*CONCLUSION@#High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34 leukemia cells in AML.

Investigation of Xiebaisan Based on Ancient Literature / 中国实验方剂学杂志

Xiebaisan, which is one of the famous classical formulas in the Catalogue of Ancient Famous Classical Formulas (The First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018, is derived from the Xiao' er Yaozheng Zhijue with definite clinical effect. By means of bibliometrics, 118 relevant ancient book data were collected, including 75 ancient books of TCM. It was found that the main symptoms of Xiebaisan had been expanded in the past dynasties. For example, the adaptive population of Xiebaisan had been extended from children to women and adults, and the scope of symptoms and signs had also been extended from pediatrics to internal medicine and gynecology. Meanwhile, the names, pathogenesis and syndromes of diseases are also described extensively, although the dosage ratio is different, the compatibility ratio of Mori Cortex, Lycii Cortex and Glycyrrhizae Radix et Rhizoma is relatively constant, and the decoction method is mostly followed by decocted power. At the same time, doctors in Ming and Qing dynasties have made a lot of general comments on explanation of this formula, but there is little controversy.

Mechanism of Traditional Chinese Medicine in Treating Drug-resistant Bacterial Infection / 中国实验方剂学杂志

The discovery of penicillin has effectively controlled the infection caused by Gram-positive bacteria. Afterwards, the research and development of antibacterial drugs has entered the golden age, and made a great contribution to human health. However, in recent years, with the increasing use of antibiotics around the world, pathogenic bacteria drive gene mutation to obtain drug resistance to ensure its survival advantage, and promote the transfer of drug-resistant genes, resulting in a sharp increase of drug-resistant bacteria. In addition, the current development speed of new antibiotics is far slower than the growth and spread speed of drug-resistant bacteria, which makes the drug-resistant crisis more serious and becomes one of the biggest threats to the global community. Compared with the same type of bacterial infection, drug-resistant bacterial infection has the characteristics of complexity and refractoriness, which causes worse clinical outcome and higher risk of death in patients, and brings severe challenges to clinical work. If the trend of bacterial drug resistance is not controlled, the crisis of no drug available will come. Therefore, it is urgent to explore effective alternative means to fight against bacterial drug resistance and reduce the harm of drug-resistant bacterial infection. Traditional Chinese medicine（TCM） has unique advantages in the treatment of infectious diseases. Compared with modern antibacterial drugs, it has the characteristics of wide sources, rich active ingredients, and is not easy to produce drug resistance. It may be an important source for screening and developing new anti-infective drugs. Therefore, it is promising to develop and utilize TCM to solve the problem of drug-resistant bacteria infection. This paper will review relevant studies in recent years in terms of interfering with the biochemical metabolism of drug-resistant bacteria to directly inhibit or kill drug-resistant bacteria, improving bacterial drug resistance to indirectly inhibit bacteria and kill bacteria, and maintaining the balance of the body and regulating the treatment of drug-resistant bacteria infection as a whole, so as to provide references for guiding clinical medication and research and development of new traditional Chinese medicines.

Textual Research on Lycii Cortex / 中国实验方剂学杂志

The research and development of classical prescriptions is an important way to promote the inheritance and innovation of traditional Chinese medicine(TCM) and promote the modernization and internationalization of TCM. It is particularly important to summarize the historical development of the composition of classical prescriptions, so as to define their origin, taste efficacy and syndrome taboos. It is also the source to ensure the safety and effectiveness of the whole prescription. As a commonly used traditional Chinese medicinal material, Lycii Cortex is widely used and has a good prospect for research and development. There are five prescriptions containing wolfberry bark in the Catalogue of Ancient Classical Prescriptions(the First Batch). There are only a few modern literatures on the development of Lycii Cortex. Therefore, this paper will summarize the development of skeleton skin alias, origin, nature, taste, meridian, efficacy, syndromes and taboos in ancient books of the previous dynasties. Textual analysis found that Lycii Cortex was first recorded in the Fifty-two Pathogenic Prescriptions. Ancient books before the Han dynasty did not mention the Chinese medicinal material named " Digupi" . There are little differences in the contents about Digupi between modern literatures and ancient books of the previous dynasties. With the changes of the times, Lycii Cortex has been rarely used, with a fault inheritance, suggesting that there are still many potential efficacy indications for clinical application. In addition to the traditional Chinese medicinal specifications, ancient books also recorded the processing methods with liquorice soup, fried, roasted, children's stool, wine soaking and steaming.

Textual Research of Mori Cortex in Classical Prescriptions / 中国实验方剂学杂志

The research and development of classical famous prescriptions is an important way to actively promote the development of traditional Chinese medicine.It is particularly important to sort out the historical evolution of the composition of traditional famous prescriptions to make clear the origin，producing areas and concocting methods of traditional Chinese medicine，which is the source of ensuring the safety and efficacy.Through literature review，it is found that at present，the research of mulberry white skin focuses on chemical composition，pharmacological mechanism and modern clinical research，and there are few ancient literature studies.Therefore，based on the ancient literature，the author conducts a comprehensive textual research on mulberry bark from its name，origin，producing areas and concocting methods and other aspects，in order to provide literature reference for the research and development of the prescription involving mulberry bark in the classic prescription.Through research，we can know that there are more than 20 aliases of mulberry bark，and the most commonly used names in modern times are "sangbaipi""sanggenbaipi""sangpi"，etc.In Tang and Song dynasties and before，mulberry bark was mainly composed of Morus alba var. alba and jisang，after Tang and Song dynasties，mulberry bark plant sources showed diversity，in modern times，Morus alba var. alba was gradually identified as the main medicinal species of mulberry bark.Therefore，it is suggested that Morus alba var. alba be selected as the plant source of mulberry bark.According to ancient books，mulberry trees are cultivated everywhere，with Jiangsu，Zhejiang and Sichuan as the best areas，and Henan and Anhui as the most popular areas in modern times.The conclusion of ancient and modern quality of mulberry bark is basically the same，the root skin is white，thick and sweet.The morden concocting methods of mulberry bark mainly include raw mulberry bark，honey mulberry bark and fried mulberry bark.According to the textual research of ancient literature，in addition to the above three kinds of medical specifications，there have been concocting methods without auxiliary materials，such as burning，baking and roasting，as well as concocting methods with auxiliary materials，such as bran roasting，rice swill soaking，honey wine roasting，etc.The concocting methods of mulberry bark used by the classical famous recipe should be selected in combination with specific drug provisions.

Effects of IDH2 Gene Mutation on Clinical Characteristics and Prognostic of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the prevalence, clinical characteristics and prognostic significance of the isocitrate dehydrogenase 2(IDH2) mutations in patients with acute myeloid leukemia(AML).@*METHODS@#The bone marrow samples of 223 patients with newly diagnosed AML confirmed by MICM typing from January 2015 to October 2018 were collected. The mutation of exon 4 of IDH2 gene was detected by direct sequancing of PCR product; the incidence and types of IDH2 gene mutation in AML patients were analyzed; the clinical characteristics of AML patients with IDH2 gene mutation were analyzed and the therapeutic efficacy for these patients was evaluated.@*RESULTS@#In a cohort of 223 AML patients, mutations were detected in 23(10.31％) patients, among them, 15 with R140Q mutations(65.22%) , 6 with R172K mutations(26.09%) and 2 with R140W mutations(8.70%). The median age in IDH2 mutated group was older than that in non.mutated group(P=0.008). The platelet level at initial diagnosis in IDH2 mutated group was higher than that in non.mutated group(P=0.010). There was no significant statistical difference between IDH2 mutated group and non.mutated group in FAB subtypes of AML(P>0.05). But the rate of IDH2 mutation in M4 and M5 was higher. The rate of IDH2 mutations was higher in AML with normal karyotype and in AML with NPM1 mutations. R140Q mutations associated with NPM1 mutations(χ=8.481，P=0.004), but R172K mutations not associated with NPM1 mutation(P>0.05). IDH2 mutated patients had a lower complete remission rate than non.mutated patients(57.14% vs 80.46%, χ=5.927，P=0.015). The complete remission rate of R140Q mutated patients was not significantly statistically different from non.mutated patients. The complete remission rate of R172K mutated patients was very significantly lower than non.mutated patients(χ=7.734，P=0.005). In the patients without NPM1 mutation, the 2 years overall survival in IDH2 mutated group was lower than in non.mutated group(36.36% vs 66.40%,χ=3.958，P=0.047), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In all patients, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(50% vs 66.88%,P>0.05), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In the patients with normal karyotype or with mutated NPM1, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(P>0.05).@*CONCLUSION@#IDH2 gene mutations are more common in AML patients at older age, higher platelets level and normal karyotype. The rate of IDH2 mutation in M4 and M5 is higher. IDH2 gene mutations associate with NPMl gene mutations, but R172K mutations not associates with NPM1mutation. IDH2 gene mutations associate with prognosis of AML patients, R140Q mutations have no effect on prognosis of patients, but R172K mutations may be the molecular markers for poor prognosis in AML patients.