The present study investigated the effect of Euphorbiae Pekinensis Radix(EPR) on intestinal flora structure before and after vinegar processing and explored the detoxification mechanism of vinegar-processed EPR. In this study, the extraction efficiency of casbane diterpenes from EPR with different solvents was investigated, and the optimal solvent was selected to enrich these components. After 14 days of intragastric administration of total diterpene extract of EPR and vinegar-processed EPR, 16 S rDNA sequencing technology was used to detect the structural changes of intestinal flora. The flora related to the intestinal toxicity of EPR was screened out based on the results of intestinal pathological damage by correlation analysis. The results showed that Soxhlet extraction with chloroform as extraction solvent could enrich Casbane diterpenes in EPR. As revealed by 16 S rDNA sequencing results, EPR could significantly change the structure of intestinal flora, which could be reversed by vinegar-processing EPR. Some intestinal flora candidates might be related to detoxification of vinegar processing. The correlation analysis of intestinal flora candidates and indexes related to intestinal mucosal injury showed that compared with EPR, vinegar-processed EPR could down-regulate the abundance of some pathogenic bacteria such as Mucispirillum, Bilophila, and Ruminiclostridium, and up-regulated some probiotics such as Enterorhabdus, Ruminococcaceae_UCG-014, Barnesiella, and Candidatus. The intestinal toxicity caused by EPR may be related to the disturbance of intestinal flora, and vinegar-processed EPR can improve intestinal flora disorder by up-regulating the abundance of probiotics and down-regulating the abundance of pathogenic bacteria to remodel the intestinal mucosal barrier and reduce toxicity.
Acetic Acid/chemistry* ; Colon ; Drugs, Chinese Herbal/chemistry* ; Gastrointestinal Microbiome ; Plant Roots

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.

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.

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.

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.

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

OBJECTIVE: To summarize the experience of percutaneous balloon pulmonary valvuloplasty for pulmonary stenosis in infants,and to evaluate its necessity,safety and effectiveness. METHODS: From January 2009 to December2018,68 cases of pulmonary stenosis were treated by percutaneous balloon pulmonary valvuloplasty. The clinical data before and after operation were analyzed retrospectively. RESULTS: The mean age was(6.34±3.6)months. The mean operation weight was(7.81±2.11)kg. The preoperative body weight/age Z score was-0.80±1.38,and growth restriction was in 22 cases(32.4%),cyanosis in 15 cases(22.1%)and tachypnea in 23 cases(33.8%). The mean right ventricular/left ventricular length-diameter ratio was 0.56±0.73 by echocardiography,the mean cardiothoracic ratio was 0.56±0.43 by chest radiography,and the average value of preoperative oxygen saturation was 94.74 ± 6.10. The mean systolic pressure ratio of right ventricle/left ventricle before operation was 0.68±0.26. After balloon dilation,the mean pressure gradient of pulmonary valve decreased from(75.57 ± 18.61)mmHg to(22.37 ± 5.21)mmHg,and the mean systolic pressure of right ventricle decreased from(83.78±22.44)mmHg to(54.16±20.81)mmHg. The immediate success rate of operation was 100%. There were no serious arrhythmia,cardiac perforation,rupture of tendon chordae,vascular injury or other complications during the operation. The proportion of mild to moderate pulmonary regurgitation was 53.3% in early stage after operation,and there was no severe regurgitation. The restenosis rate was 2.94% during the follow-up period of 3 months to 10 years. The pulmonary valve regurgitation degree of 32 children who were followed up for more than 5 years did not further aggravate,and no specific management was carried out. No obvious right ventricular dysfunction was found in all patients. Compared with the toddlerhood infants undergoing PBPV in our center,the babyhood infants had obvious clinical symptoms and serious condition. The early and medium-long-term follow-up after operation was satisfactory. There was no significant difference in the effect of operation in the low-weight or low-age infants in babyhood. CONCLUSION: PBPV is necessary for the treatment of pulmonary stenosis in infants. The technique is safe and feasible,and the follow-up results are effective.

OBJECTIVE: To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP). METHODS: A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events. RESULTS: Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P<0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group (P<0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated. CONCLUSIONS Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP. [ClinicalTrials.gov identifier: NCT03037047].

Through analysis of Lau Wan Yee's published papers,monographs,conference speeches,research designs / revisions for major hospitals in China,combined with analysis of articles revised by Academician Lau in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University for the past decade,authors came up with 9 points in Academician Lau's research ideas.Academician Lau has played a huge and leading role in improving clinical skills and scientific research levels,as well as in development and internationalization of hepatobiliary and pancreatic surgery in China.To summarize the research ideas of Lau is of great importance to the future generations of surgeons.