Exogenous methionine contributes to reversing the resistance of Streptococcus suis to macrolides.

Streptococcus suis (S. suis) has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Multidrug-resistant Streptococcus suis is becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. In the present study, an untargeted metabolomics analysis showed that the significant decrease in methionine content and the methionine biosynthetic pathway were significantly affected by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis in drug-resistant S. suis. The addition of L-methionine restored the bactericidal activity of macrolides, doxycycline, and ciprofloxacin on S. suis in vivo and in vitro. Further studies showed that the exogenous addition of methionine affects methionine metabolism by reducing S-adenosylmethionine synthetase activity and the contents of S-adenosylmethionine, S-adenosyl homocysteine, and S-ribose homocysteine. Methionine can decrease the total methylation level and methylesterase activity in multidrug resistant S. suis. The drug transport proteins and efflux pump genes were significantly downregulated in S. suis by exogenous L-methionine. Moreover, the exogenous addition of methionine can reduce the survival of S. suis by affecting oxidative stress and metal starvation in bacteria. Thus, L-methionine may influence the development of resistance in S. suis through methyl metabolism and metal starvation. This study provides a new perspective on the mitigation of drug resistance in S. suis.IMPORTANCEBacterial antibiotic resistance has become a severe threat to human and animal health. Increasing the efficacy of existing antibiotics is a promising strategy against antibiotic resistance. Here, we report that L-methionine enhances the efficacy of macrolides, doxycycline, and ciprofloxacin antibiotics in killing Streptococcus suis, including multidrug-resistant pathogens. We investigated the mechanism of action of exogenous methionine supplementation in restoring macrolides in Streptococcus suis and the role of the methionine cycle pathway on methylation levels, efflux pump genes, oxidative stress, and metal starvation in Streptococcus suis. It provides a theoretical basis for the rational use of macrolides in clinical practice and also identifies a possible target for restoring drug resistance in Streptococcus suis.

Guideline on Establishing Diagnostic Criteria for Chinese Medicine Syndromes.

AIM: To formulate the guideline for the development of diagnostic criteria for Chinese medicine syndromes, which can contribute to standardization of development of Chinese medicine syndrome diagnostic standards. METHODS: We embark into account on the development of Guideline on Establishing Diagnostic Criteria for Chinese Medicine Syndromes through Delphi method with reference to the existing technical system of diagnostic criteria for Chinese medicine syndromes and relevant criteria. RESULTS: Our guideline specifies principles, methods, and procedures for the formulation of diagnostic criteria for Chinese medicine syndromes. CONCLUSIONS: It is a comprehensive and systematic evidence-based guideline, and we hope this guideline can be applied as a reference in developing diagnostic criteria for Chinese medicine syndromes in other disciplines. It is also applicable to the formulation of diagnostic criteria for relevant clinical, educational, and scientific research by hospitals, institutes, and academies.

Identification and expression analysis of invertase family genes during grape (Vitis vinifera L.) berry development under CPPU and GA treatment.

Sugar is crucial for grape berry, whether used for fresh food or wine. However, berry enlargement treatment with forchlorfenuron (N-(2-chloro4-pyridyl)-N'-phenylurea) (CPPU, a synthetic cytokinin) and gibberellin (GA) always had adverse effects on sugar accumulation in some grape varieties, especially CPPU. Therefore exploring the molecular mechanisms behind these adverse effects could provide a foundation for improving or developing technology to mitigate the effects of CPPU/GA treatments for grape growers. In the present study, invertase (INV) family, the key gene controlling sugar accumulation, was identified and characterized on the latest annotated grape genome. Their express pattern, as well as invertase activity and sugar content, were analyzed during grape berry development under CPPU and GA3 treatment to explore the potential role of INV members under berry enlargement treatment in grapes. Eighteen INV genes were identified and divided into two sub-families: 10 neutral INV genes (Vv-A/N-INV1-10) and 8 acid INV genes containing 5 CWINV (VvCWINV1-5) and 3 VIN (VvVIN1-3). At the early development stage, both CPPU and GA3 treatment decreased the hexose level in berries of 'Pinot Noir' grape, whereas the activity of three types inverstase (soluble acid INV, insoluble acid INV, and neutral INV) increased. Correspondingly, most of INV members were up-regulated by GA3 /CPPU application at least one sampling time point during early berry development, including VvCWINV1, 2, 3, 4, 5, VvVIN1, 2, 3 and Vv-A/N-INV1, 2, 5, 6, 7, 8, 10. At maturity, the sugar content in CPPU-treated berries is still lower than that in the control. Soluble acid INV and neutral INV, rather than insoluble acid INV, presented lower activity in CPPU-treated berries. Meanwhile, several corresponding genes, such as VvVIN2 and Vv-A/N-INV2, 8, 10 in ripening berries were obviously down-regulated by CPPU treatment. These results suggested that most of INV members could be triggered by berry enlargement treatment during early berry development, whereas VvVINs and Vv-A/N-INVs, but not VvCWINVs, could be the limiting factor resulting in decreased sugar accumulation in CPPU-treated berries at maturity. In conclusion, this study identified the INV family on the latest annotated grape genome and selected several potential members involving in the limit of CPPU on final sugar accumulation in grape berry. These results provide candidate genes for further study of the molecular regulation of CPPU and GA on sugar accumulation in grape.

[Distribution characteristics of traditional Chinese medicine syndromes in 4 367 adult influenza patients: a Meta-analysis].

OBJECTIVE: To systematically evaluate the distribution characteristics of traditional Chinese medicine (TCM) syndromes in adult influenza patients and to provide a basis for the TCM syndrome differentiation of influenza. METHODS: The CNKI, CBM, Wanfang, VIP, PubMed, Embase, Cochrane Library databases were searched to collect cross-sectional studies on the distribution pattern of TCM syndromes in adult patients with influenza. The risk of bias assessment tool for cross-sectional studies developed by the Joanna Briggs Institute (JBI) evidence-based health care center was used to evaluate the literature quality, and the Stata 15.1 software was used to conduct a Meta-analysis of the pooled effect sizes of the included studies. RESULTS: A total of 11 studies with 4 367 influenza patients were included. Quality assessment results of JBI showed that the risk bias was higher in the sample size calculation, and the description of sampling modalities and response rate was unclear. There were 17 influenza syndromes after specification, and a single group rate Meta-analysis was performed of the syndromes with ≥ 50 incident cases showed that there were 9 syndromes with an incidence ≥ 10% and statistical significance, the top 5 syndromes were syndrome of wind and heat invading the defense [n = 1 583, RATE = 34.3%, 95% confidence interval (95%CI) was 22.2%-46.3%], syndrome of exterior cold and interior heat (n = 1 122, RATE = 36.1%, 95%CI was 21.2%-51.1%), syndrome of wind-cold fettering the exterior (n = 860, RATE = 19.4%, 95%CI was 10.7%-28.0%), syndrome of heat and toxin in the lung (n = 217, RATE = 17.1%, 95%CI was 9.1%-25.0%), and syndrome of disease involving both defense phase and qi phase (n = 184, RATE = 38.8%, 95%CI was 14.2%-63.5%). The results of the subgroup analysis in different geographical regions showed that the frequency of distribution of syndrome of wind and heat invading the defense and heat and toxin in the lung was higher in the South (RATE: 36.5%, 18.6%) than in the North (RATE: 30.9%, 15.4%), and the frequency of distribution of syndrome of wind-cold fettering the exterior and exterior cold and interior heat in the North (RATE: 23.8%, 40.1%) was higher than that in the South (RATE: 15.7%, 32.3%). CONCLUSIONS: There are 9 common TCM syndromes of influenza, including wind and heat invading the defense syndrome, exterior cold and interior heat syndrome, wind-cold fettering the exterior syndrome, heat and toxin in the lung syndrome, disease involving both defense phase and qi phase syndrome, wind and heat complicated by dampnessinvading the surface syndrome, wind and cold complicated by dampnessinvading the surface syndrome, defense phase syndrome and dampness and heatinvading the surface syndrome, which can provide a reference for the TCM syndrome differentiation and treatment of influenza.

Relationship between Dining Place, Iodine Source, and Iodine Nutrition in School-Age Children: A Cross-Sectional Study in China / 生物医学与环境科学（英文）

OBJECTIVE@#This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children.@*METHODS@#School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables.@*RESULTS@#Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status.@*CONCLUSION@#Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.

Mechanisms of traditional Chinese medicine formulas and active ingredients in regulation of macrophage subsets involved in inflammation and repair of coronary heart disease / 中国中药杂志

Coronary artery disease(CAD) caused by atherosclerosis(AS) is a major contributor to the global burden of disease. The pathogenesis of CAD is complex, and the subset and function of cardiac macrophages are important factors affecting the occurrence and development of AS and the prognosis of CAD. Recent studies have shown that some traditional Chinese medicine(TCM) formulas and active ingredients can regulate macrophage subsets involved in the inflammation, injury, and repair process of CAD. This paper summarized the significant role of macrophages in AS and myocardial infarction. Based on the plasticity of macrophages, this paper elaborated that traditional Chinese medicine prevented and attenuated AS by regulating macrophage subsets, reducing the level of inflammatory factors, and promoting macrophage autophagy.Traditional Chinese medicine participated in the cardiac repair process after myocardial infarction by accelerating the recruitment of M2 macrophages, inhibiting the polarization of M1 macrophages mediated by glycolysis, inhibiting M1 macrophage-mediated cardiac nerve remodeling, and promoting M2 macrophage-mediated angiogenesis. In addition, in vitro studies on the regulation of macrophage subsets by the active ingredients of traditional Chinese medicine were also reviewed. It was pointed out that nuclear factor kappa B(NF-κB), adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt), chemokine(C-C motif) ligand 2/C-C chemokine receptor type 2(CCL2/CCR2) were the key targets and pathways for the regulation of macrophages by TCM.

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Phenylpropanoids from Brachybotrys paridiformis maxim. Ex oliv. And their anti-HBV activities (II).

Five undescribed phenylpropanoids, one undescribed phenolic glucoside, and sixteen known compounds were isolated from Brachybotrys paridiformis Maxim. Ex Oliv. The undescribed compounds were named brachoside B-C, brach acid A-B, brachnan A, and brachin D, respectively. Additionally, the anti-hepatitis B virus activities of all isolated compounds were studied. Among them, brachnan A, brach acid A, globoidnan A, 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxy-phenyl)-naphthalene, and 3,4-dihydroxybenzaldehyde showed significant anti-hepatitis B virus activities.

Association of blood lead and blood selenium with serum high-sensitivity C-reactive protein among Chinese adults aged 19 to 79 years / 中华流行病学杂志

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Quality value transfer of substance benchmarks in Sanpian Decoction / 中国中药杂志

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

[Selection of q RT-PCR reference genes for Amomum tsaoko seeds during dormancy release].

Freshly collected seeds of Amomum tsaoko demonstrate obvious dormancy. Therefore, the selection of stable reference genes during seed dormancy release is very important for the subsequent functional research of related genes. In this study, ten commonly used reference genes(GAPDH, 40S, actin, tubulin, EIF4A-9, EIF2α, UBC, UBCE2, 60S, and UBQ) were selected as candidates for quantitative Real-time polymerase chain reaction(qRT-PCR) of the embryo samples of A. tsaoko at different dormancy release stages. Three kinds of software(BestKeeper, geNorm, and Normfinder) and the Delta CT method were used to evaluate the expression stability of the candidate reference genes, and the RefFinder online tool was employed to integrate the results and generate a comprehensive ranking. The results showed that the expression levels of the ten candidate reference genes differed greatly in different embryo samples. GAPDH and UBC had high expression levels, as manifested by the small Ct values. GeNorm identified 40S and UBCE2 as the most stable genes. NormFinder ranked EIF2α as the most stable gene and UBC as the least stable gene. UBCE2 was found to be the most stable gene and actin the least stable one by BestKeeper. Delta CT analysis suggested that the expression of 40S was most stable. UBCE2 was recommended as the most stably expressed gene by RefFinder. Thus, UBCE2 is the ideal reference gene for qRT-PCR analysis of A. tsaoko seeds at different dormancy release stages. The results may lay a foundation for analyzing the expression of related genes during seed dormancy release of A. tsaoko.

Role of Acupuncture in the Treatment of COPD: An Overview of Systematic Reviews.

BACKGROUND: Since consistent evidence on the effectiveness of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD) is not available, this overview aims to summarize and critically evaluate the methodological and evidence quality of systematic reviews (SRs) on this topic. METHODS: Eight electronic databases were searched to identify relevant SRs of the use of acupuncture in the treatment of COPD from inception to January 2021. Two researchers independently screened the literature, extracted the data, and cross-checked the data. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) list was used to assess the methodological quality of SRs. The Grades of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence for the outcomes of interest. RESULTS: Nine SRs that conducted quantitative syntheses were included in this overview. The methodological quality of the SRs and the quality of evidence for the main outcome measures were generally unsatisfactory. Only 2 SRs were rated as low methodological quality by AMSTAR 2, and the remaining SRs were rated as critically low quality. The key limitations of the SRs were lack of a protocol and registration or a list of excluded studies. We did not find high-quality evidence to confirm the effectiveness of acupuncture for COPD, and the main reason was that the qualitative data synthesis relied on trials with small sample sizes and critically low quality. CONCLUSION: Acupuncture appears to be an effective therapeutic method for COPD, but the credibility of the results is limited owing to the generally low methodological quality and evidence quality of the included SRs. Further rigorous and comprehensive studies are required to provide robust evidence and draw definitive conclusions.

Krishnolides E-K: New limonoids from the Krishna mangrove Xylocarpus moluccensis.

Seven new limonoids, named krishnolides E-K (1-7), including three khayanolides, two mexicanolides, a derivative of trangmolin A, and an andirobin, were isolated from seeds of the Indian Krishna mangrove, Xylocarpus moluccensis. The structures of these limonoids were established by HRESIMS, extensive NMR investigations, and X-ray crystallography. Most notably, the absolute configurations of 1, 5, 6, and 7 were unequivocally determined by single-crystal X-ray diffraction analyses (Cu Kα). Krishnolide F (2) exhibited significant agonistic effects on human pregnane-X-receptor (hPXR) at the concentration of 10.0 µM. Molecular docking revealed that 2 could bind a helix near the region of the Helix 12 of hPXR. Polar contribution could be electrostatic effects from the formation of two stable protein-ligand hydrogen bonds between Gln285/1-OH and His407/1-OH, respectively. This is the first report of agonistic effects of a khayanolide-type limonoid on hPXR.

An integrated strategy toward comprehensive characterization and quantification of multiple components from herbal medicine: An application study in Gelsemium elegans / 中草药·英文版

Objective: To develop a powerful integrated strategy based on liquid chromatography coupled with mass spectrometry (LC-MS) systems for the comprehensive characterization and quantification of multiple components of herbal medicines. Methods: Firstly, different mobile phase additives, analysis time, and MS acquisition modes were orthogonally tested with liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) in order to detect as many components of Gelsemium elegans as possible with high peak intensity. Secondly, several data mining strategies, including database searching, diagnostic ion filtering and neutral loss filtering, were utilized to perform chemical profiling. Subsequently, this study focused on the quantification and validation of the performance of a liquid chromatography-triple mass spectrometry (LC-QqQ/MS) assay based on derivative multiple reaction monitoring (DeMRM). Results: A total of 147 components from G. elegans were characterized, among them 116 nontarget components were reported for the first time. A sensitive and reproducible LC-QqQ/MS method was successfully developed and validated for the simultaneous relative quantification of 41 components of G. elegans. This LC-QqQ/MS method was then applied to compare the contents of components in the roots, stems and leaves. Conclusion: The present integrated strategy would significantly contribute to chemical studies on herbal medicine, and its utility could be extended to other research fields, such as metabolomics, quality control, and pharmacokinetics.

Correlation between estrogen levels and coronary heart disease with kidney deficiency and intervention effect of kidney-tonifying traditional Chinese medicine / 中国中药杂志

With the process of urbanization and population aging in China, the burden of cardiovascular disease and the incidence of coronary heart disease among postmenopausal women have greatly increased. Studies have found that the incidence of coronary heart disease in postmenopausal women is closely related to the level of estrogen, but there are still difficulties of low efficiency and large side effects in current therapies. Kidney deficiency has a strong correlation with reproductive development and overall function. The clinical manifestations and characteristics of postmenopausal coronary heart disease patients conform to the pathogenesis of kidney deficiency in traditional Chinese medicine. The kidney-invigorating method has a good efficacy in treating postmenopausal coronary heart disease patients. This paper summarizes clinical and pharmacological evidences, expounds the relationship between kidney deficiency and the level of estrogen, and the pathological mechanism of the kidney-tonifying method in the treatment of coronary heart disease, and defines the clinical efficacy and advantages of the kidney-tonifying method. The method may become an effective method to prevent and treat postmenopausal coronary heart disease, and is expected to benefit patients with coronary heart disease better.

Analysis on quality value transmitting of substance benchmark of Houpo Wenzhong Decoction / 中国中药杂志

By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.

[Correlation between symptoms and their contribution to syndrome based on association rule combined with Bayesian network: syndrome of lung damp-heat accumulation in coronavirus disease 2019].

OBJECTIVE: To explore the correlation between symptoms and their contribution to syndrome based on syndrome of lung damp-heat accumulation in coronavirus disease 2019 (COVID-19), thus to provide methodological basis for the syndrome diagnosis. METHODS: Based on 654 clinical investigation questionnaires data of COVID-19 patients, a model based on syndrome of lung damp-heat accumulation was set. Using SPSS Modeler 14.1 software, association rules and Bayesian network were applied to explore the correlation between symptoms and their contribution to syndrome. RESULTS: There were 121 questionnaires referring to syndrome of lung damp-heat accumulation in total 654 questionnaires. The symptoms with frequency > 40% were fever (53.72%), cough (47.93%), red tongue (45.45%), rapid pulse (43.80%), greasy fur (42.15%), yellow tongue (41.32%), fatigue (40.50%) and anorexia (40.50%). Association rule analysis showed that the symptom groups with strong binomial correlation included fever, thirst, chest tightness, shortness of breath, cough, yellow phlegm, etc. The symptom groups with strong trinomial correlation included cough, yellow phlegm, phlegm sticky, anorexia, vomiting, heavy head and body, fever, thirst, fatigue, etc. Based on SPSS Modeler 14.1 software, with syndrome of lung damp-heat accumulation (yes = 1, no = 0) as target variable, and the selected symptoms with frequency > 15.0% as input variables, the Bayesian network model was established to obtain the probability distribution table of symptoms (groups), in which there was only one parent node (the upper node of each input variable) of fever, and the conditional probability was 0.54. The parent node of cough had yellow phlegm and syndrome of lung damp-heat accumulation, indicating that there was a direct causal relationship between cough and yellow phlegm in syndrome of lung damp-heat accumulation, and the conditional probability of cough was 0.99 under the condition of yellow phlegm. The common symptom groups and their contribution to syndrome were as follows: fever and thirsty (0.47), cough and yellow phlegm (0.49), chest tightness and polypnea (0.46), anorexia and heavy cumbersome head and body (0.61), yellow greasy fur and slippery rapid pulse (0.95). CONCLUSIONS: It is feasible and objective to analyze the correlation between symptoms and their contribution to syndromes by association rules combined with Bayesian network. It could provide methodological basis for the syndrome diagnosis.

[Study on traditional Chinese medicine common syndrome characteristic of coronavirus disease 2019 based on latent structure combined with system clustering analysis].

OBJECTIVE: To investigate traditional Chinese medicine (TCM) common syndrome characteristic of coronavirus disease 2019 (COVID-19), thus providing evidence for clinical differentiation. METHODS: The COVID-19 TCM treatment plan and syndrome related literature published before February 24, 2020 was searched and a database was established. TCM common syndrome characteristics of COVID-19 were analyzed by the method of latent structure and system clustering combined with frequency and constituent ratio, which were conducted by Lantern 5.0 and SPSS 20.0. RESULTS: Forty-two literatures about treatment plans, and 212 syndromes records were enrolled. Latent structure model was established based on 53 symptoms with frequency over 10, and 14 latent variables and 7 syndromes were concluded by comprehensive clustering, including syndrome of pathogenic heat invading lung, internal block and outward desertion, syndrome of dampness heat accumulating lung, syndrome of Qi and Yin deficiency, syndrome of epidemic virus closing lung, syndrome of cold dampness closing lung and syndrome of Qi deficiency of lung and spleen. Factor analysis was conducted for 53 symptoms, which were reported more than 10 times, and 14 common factors were obtained. Symptoms with load coefficient over 0.3 were clustered and 6 syndromes were obtained, including syndrome of epidemic virus closing lung, syndrome of pathogenic heat invading lung, syndrome of Qi and Yin deficiency, internal block and outward desertion, syndrome of cold dampness closing lung, and syndrome of dampness heat accumulating lung. The literatures included 25 syndromes, and the syndromes with constituent ratio over 5% were internal block and outward desertion (14.62%), syndrome of epidemic virus closing lung (13.68%), syndrome of dampness heat accumulating lung (12.74%), syndrome of Qi deficiency of lung (10.85%), spleen and syndrome of cold dampness closing lung (8.50%), syndrome of Qi and Yin deficiency (8.50%), syndrome of pathogenic heat invading lung (8.02%) and syndrome of dampness repressing defensive Qi of lung (5.66%). Eighty-seven symptoms whose cumulative frequency was 2 838 were referred, including greasy fur (5.25%), fever (4.83%), red tongue (4.37%), rapid pulse (3.74%) and fatigue (3.46%). According to the results above, the common syndromes and their symptoms of COVID-19 were: (1) syndrome of pathogenic heat invading lung: fever, cough, throat-drying, headache, all of the body distressed and constipation, etc.; (2) syndrome of cold dampness closing lung: aversion to cold, all of the body distressed, nausea and vomiting, abdominal distention and loose stool, etc.; (3) syndrome of dampness heat accumulating lung: cough, sticky phlegm, anorexia, thirst without desire to drink and constipation, etc.; (4) syndrome of epidemic virus closing lung: fever, cough, yellow phlegm, wheezing, suffocation and purple lips, etc.; (5) internal block and outward desertion: coma, feel fidgety, suffocation, sweating and feel cold and purple lips, etc.; (6) syndrome of Qi and Yin deficiency: dry cough, sweating, fatigue, thirsty, feverish feeling in palms and soles and loose stool, etc.; (7) syndrome of Qi deficiency of lung and spleen: cough, wheezing, sweating, fatigue, nausea and vomiting, and loose stool, et al. CONCLUSIONS: The common syndromes of COVID-19 were syndrome of pathogenic heat invading lung, syndrome of cold dampness closing lung, syndrome of dampness heat accumulating lung, syndrome of epidemic virus closing lung, internal block and outward desertion, syndrome of Qi and Yin deficiency and syndrome of Qi deficiency of lung and spleen. This study could provide reference for clinical differentiation.

A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action for the Rougui-Fuzi Herb Pair in the Treatment of Cardiocerebral Vascular Diseases.

Cardiocerebral vascular diseases (CCVDs) are the main reasons for high morbidity and mortality all over the world, including atherosclerosis, hypertension, myocardial infarction, stroke, and so on. Chinese herbs pair of the Cinnamomum cassia Presl (Chinese name, rougui) and the Aconitum carmichaelii Debx (Chinese name, fuzi) can be effective in CCVDs, which is recorded in the ancient classic book Shennong Bencao Jing, Mingyibielu and Thousand Golden Prescriptions. However, the active ingredients and the molecular mechanisms of rougui-fuzi in treatment of CCVDs are still unclear. This study was designed to apply a system pharmacology approach to reveal the molecular mechanisms of the rougui-fuzi anti-CCVDs. The 163 candidate compounds were retrieved from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). And 84 potential active compounds and the corresponding 42 targets were obtained from systematic model. The underlying mechanisms of the therapeutic effect for rougui-fuzi were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, component-target-disease (C-T-D) and target-pathway (T-P) networks were constructed to further dissect the core pathways, potential targets, and active compounds in treatment of CCVDs for rougui-fuzi. We also constituted protein-protein in interaction (PPI) network by the reflect target protein of the crucial pathways against CCVDs. As a result, 21 key compounds, 8 key targets, and 3 key pathways were obtained for rougui-fuzi. Afterwards, molecular docking was performed to validate the reliability of the interactions between some compounds and their corresponding targets. Finally, UPLC-Q-Exactive-MSE and GC-MS/MS were analyzed to detect the active ingredients of rougui-fuzi. Our results may provide a new approach to clarify the molecular mechanisms of Chinese herb pair in treatment with CCVDs at a systematic level.

The Active Ingredients Identification and Antidiarrheal Mechanism Analysis of Plantago asiatica L. Superfine Powder.

Plantago asiatica L. is a natural medicinal plant that has been widely used for its various pharmacological effects such as antidiarrheal, anti-inflammatory, and wound healing. This study aims to explore the antidiarrheal active ingredients of Plantago asiatica L. that can be used as quality markers to evaluate P. asiatica L. superfine powder (PSP). Molecular docking experiment was performed to identify the effective components of P. asiatica L., which were further evaluated by an established mouse diarrhea model. Na+/K+-ATPase and creatine kinase (CK) activities and the Na+/K+ concentrations were determined. The gene expression of ckb and Atp1b3 was detected. PSP was prepared and evaluated in terms of the tap density and the angle of repose. The structures of PSPs of different sizes were measured by infrared spectra. The active ingredient contents of PSPs were determined by HPLC. The results indicated that the main antidiarrheal components of P. asiatica L. were luteolin and scutellarein that could increase the concentration of Na+ and K+ by upregulating the activity and gene level of CK and Na+/K+-ATPase. In addition, luteolin and scutellarein could also decrease the volume and weight of small intestinal contents to exert antidiarrheal activity. Moreover, as the PSP size decreased from 6.66 to 3.55 µm, the powder tended to be amorphous and homogenized and of good fluidity, the content of active compounds gradually increased, and the main structure of the molecule remained steady. The optimum particle size of PSP with the highest content of active components was 3.55 µm, and the lowest effective dose for antidiarrhea was 2,000 mg/kg. Therefore, the antidiarrheal active ingredients of PSP were identified as luteolin and scutellarein that exert antidiarrheal activity by binding with Na+/K+-ATPase. PSP was successfully prepared and could be used as a new dosage form for the diarrhea treatment.