A novel enzyme-based functional correlation algorithm for multi-omics reveals the potential mechanisms of traditional Chinese medicines: Taking Jian-Pi-Yi-Shen formula as an example.

The integrated analysis of host metabolome and intestinal microbiome is an opportunity to explore the complex therapeutic mechanisms of traditional Chinese medicines. Currently, researchers mainly employ various statistical correlation analytical methods to investigate metabolome-microbiome correlations. However, these conventional correlation techniques often focus on statistical correlations and their biological meanings are always ignored, especially the functional relevance between them. Here, we developed a novel enzyme-based functional correlation (EBFC) algorithm to further improve the interpretability and the identified scope of microbe-metabolite correlations based on the conventional Spearman's analysis. The proposed EBFC algorithm is successfully utilized to reveal the therapeutic mechanisms of Jian-Pi-Yi-Shen (JPYS) formula on the treatment of adenine-induced chronic kidney disease (CKD) rats. JPYS, a TCM formula for treating CKD, has beneficial clinical effects. We tentatively revealed the potential mechanism of JPYS for treating CKD rats from the perspective of the serum metabolome, gut microbiome, and their interactions. Specifically, 11 metabolites and 19 bacterial genera in the CKD rats were significantly regulated to approaching normal status after JPYS treatment, suggesting that JPYS could ameliorate the pathological symptoms of CKD rats by reshaping the disturbed metabolome and gut microbiota. Further correlation analysis between the significantly perturbed metabolites, microbiota, and the related enzymes provided more strong evidence for the study of host metabolism-microbiota interactions and the therapeutic mechanism of JPYS on CKD rats. In conclusion, these findings will help us to deeply understand the pathogenesis of CKD and provide new insights into the therapeutic mechanism of JPYS.

Comprehensive assessment of the utilization of manure in China's croplands based on national farmer survey data.

China's rapid increase in mass excreta and its environmental discharge have attracted substantial attention. However, cropland as a main destination of excreta utilization has not been extensively evaluated. Here, a national survey was used to assess the utilization of manure in croplands across China. The data included the inputs of manure nitrogen (N), phosphorus (P), and potassium (K) for cereals, fruits, vegetables, and other crops, along with the manure proportion of total N, P, and K inputs at the county level. The results showed that the manure N, P, and K inputs were 6.85, 2.14, and 4.65 million tons (Mt), respectively, constituting 19.0%, 25.5%, and 31.1% of the total N, P, and K, respectively. The spatial distribution of the manure proportion of total inputs was lower in Eastern China and higher in Western China. The results provide a detailed description of the utilization of manure nutrients in agricultural areas throughout China, which will serve as basic support for policymakers and researchers involved in future agricultural nutrient management in China.

The association between serum folate and gestational diabetes mellitus: a large retrospective cohort study in Chinese population.

OBJECTIVE: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. DESIGN: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage-response relationship between serum folate and the risk of GDM. SETTING: A sigle, urban hospital in Shanghai, China. PARTICIPANTS: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. RESULTS: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P-for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs). CONCLUSIONS: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention.

Polyphenols in Highland Barley Tea Inhibit the Production of Advanced Glycosylation End-Products and Alleviate the Skeletal Muscle Damage.

SCOPE: Highland barley tea is a kind of caffeine-free cereal tea. Previous studies have shown that it is rich in polyphenol flavonoids. Here, the effect of Highland barley tea polyphenols (HBP) on the production of advanced glycosylation end-products and alleviate the skeletal muscle damage is systematically investigated. METHODS AND RESULTS: HBP effectively inhibits the formation of AGEs in vitro, and 12 phenolic compounds are identified. In addition, d-galactose is used to construct a mouse senescence model and intervenes with different doses of HBP. It is found that high doses of HBP effectively inhibit AGEs in serum and flounder muscle species and increased muscle mass in flounder muscle; also, high doses of HBP increase the expression of the mitochondrial functional protein SIRT3 and decrease the expression of myasthenia-related proteins. Furthermore, cellular experiments show that AGEs can significantly increase oxidative stress in skeletal muscle. CONCLUSION: These data indicate that the relationship between the biological activity and HBP properties is relevant since Highland barley can be a potential functional food to prevent AGEs-mediated skeletal muscle damage.

Phosphorus vacancy-engineered Ce-doped CoP nanosheets for the electrocatalytic oxidation of 5-hydroxymethylfurfural.

The electrooxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furanedioic acid (FDCA) has received increasing attention. To achieve satisfactory electrooxidation of HMF, the development of an efficient electrocatalyst is particularly critical. Herein, porous Ce-CoP nanosheets integrating Ce doping and P vacancies are designed through a deep eutectic solvent approach, and they allow the excellent electrocatalytic oxidation of HMF to FDCA in 1 M KOH electrolyte with 100% HMF conversion, 98% FDCA yield, and a faradaic efficiency of 96.4% at low potential.

An in-house database-driven untargeted identification strategy for deep profiling of chemicalome in Chinese medicinal formula.

Deep profiling of chemicalome in Chinese medicinal formulas is vital for disclosing the secret underlying their effectiveness. To address this issue, an in-house database-driven untargeted identification strategy was proposed with the use of ultra-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry. Firstly, an in-house mass spectral database for the analyzed herbs was constructed, and database querying was performed for rapid recognition of known compounds. Secondly, a chemical diagnostic characteristics algorithm was originally developed for deep mining unrecorded ions, and thus expanding coverage of components beyond the database. Additionally, we proposed evaluation criteria for the untargeted identification of compounds with different confidence levels. As a case study, the integrated strategy was applied to comprehensively characterize complex multi-type components in Gegen-Qinlian Decoction. A total of 381 compounds were characterized and annotated with four different confidence levels, and 88.40% of these annotated compounds were successfully re-identified in triplicate analyses with a different instrument. The integrated strategy was demonstrated powerful in deep profiling of chemicalome in Chinese medicinal formulas with higher throughput, analytical sharpness, and lower omission ratios.

Clinical effects of the combination of Traditional Chinese and Western Medicines on coronavirus disease 2019: a systematic review and Meta-analysi.

OBJECTIVE: To explore the clinical efficacy of the combination of Traditional Chinese and Western Medicines for the treatment of coronavirus disease 2019 (COVID-19). METHODS: Studies were identified in six popular medical databases. RESULTS: Thirteen studies were included. The results showed that combined treatment with Traditional Chinese and Western Medicines can reduce the probability of progression from mild to severe disease [RR = 0.34, 95% confidence interval (CI) (0.18, 0.65)] (P = 0.001) and improve the clinical cure rate [RR = 0.17, 95% CI (0.05, 0.28)] (P = 0.004). The use of an integrated treatment strategy shortened the time to the remission of fever [WMD = －1.27, 95% CI (－1.67, －0.92)](P < 0.001) and improved the incidences of the disappearance of fever and fatigue [RR = 1.25, 95% CI (1.06, 1.47) (P = 0.007); RR = 1.49, 95% CI (1.13, 1.97) (P = 0.004)]. CONCLUSION: A combined treatment strategy is effective for COVID-19.

Crocins: A comprehensive review of structural characteristics, pharmacokinetics and therapeutic effects.

Crocins, as a kind of water-soluble carotenoid pigment, are a series of ester compounds formed from crocetin and gentibiose or glucose, and mainly distributed among Crocus sativus L. (CSL), Gardenia jasminoides Ellis. (GJE). Crocins exhibit a wide range of pharmacological effects on neurodegeneration, cardiovascular disease, cerebrovascular disease, depression, liver disease, arthritis, tumor, diabetes, etc. This review systematically discussed the pharmacologic study of crocins in the aspect of structural characteristic and pharmacokinetics, and summarized the mechanism of treating disease. It summarized the abundant research of crocins from 1984 to 2020 based on the above aspects, which provide a reference for the deeply development and application of crocins.

[Quality changes of Gardeniae Fructus Praeparatus processed by different frying methods: a color-component correlation analysis].

The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.

Investigation of Potential Pharmacodynamic Substances and Mechanism of Gardeniae Fructus in Treatment of Ischemic Stroke Based on HPLC-Q-TOF-MS/MS and Network Pharmacology / 中国实验方剂学杂志

Objective:Combined with high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （HPLC-Q-TOF-MS/MS） and network pharmacology， to predict the target and potential mechanism of Gardeniae Fructus in the treatment of cerebral ischemia. Method:HPLC-Q-TOF-MS/MS was used to identify the chemical constituents of Gardeniae Fructus according to the retention time， relative molecular weight， secondary mass spectrometry fragmentation and other information of chromatographic peaks， and combined with literature data. The targets of main active ingredients in Gardeniae Fructus were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction database. The potential targets of Gardeniae Fructus against cerebral ischemia were obtained through Online Mendelian Inheritance in Man （OMIM）， GeneCards and Kyoto Encyclopedia of Genes and Genomes （KEGG）. Gene ontology （GO） function enrichment and KEGG pathway analysis of potential targets were analyzed with the DAVID 6.8. Cytoscape 3.6.0 software was used to construct the network of active components-targets-pathways. At last， Discovery Studio 2016 software was applied in the molecular docking verification between the key active ingredients and potential protein targets. Result:A total of 40 chemical constituents in Gardeniae Fructus were identified， including iridoids， diterpenoid pigments， organic acids， monoterpenoids and other components. According to the main active ingredients， 208 potential targets were predicted， 560 disease targets related to cerebral ischemia were retrieved， 59 key targets were selected by mapping component targets with disease targets. These targets could act on key target proteins such as tumor necrosis factor （TNF）， Caspase-3 （CASP3） and CASP8， and participate in the regulation of TNF， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， hypoxia inducible factor 1 （HIF-1） and other signal pathways. Molecular docking results showed that geniposide could interact with targets of prostaglandin G/H synthase 2 （PTGS2）， TNF<italic> </italic>and nuclear transcription factor-<italic>κ</italic>B p65 （RELA）， crocin Ⅰ could interact with interleukin-2 （IL-2）. Conclusion:Geniposide， crocin Ⅰ and other ingredients in Gardeniae Fructus can play a role of anti-inflammatory and inhibiting apoptosis to prevent or treat cerebral ischemic diseases by up-regulating protein expression level of RELA and IL-2， down-regulating protein expression level of TNF， CASP8， CASP3 and matrix metalloproteinase 2 （MMP2）， and regulating TNF， PI3K/Akt and HIF-1 signaling pathways.

Quality changes of Gardeniae Fructus Praeparatus processed by different frying methods: a color-component correlation analysis / 中国中药杂志

The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.

In silico production of relative correction factor for the quantitative analysis of multi-components by single marker method.

INTRODUCTION: Traditional methods to derive experimentally-generated relative correction factors (RCFs) for the quantitative analysis of herbal multi-components by single marker (QAMS) method require reference standards and multiple validations with different instruments and columns, which hampers high throughput implementation. OBJECTIVES: To effectively reduce the application amounts of raw material and provide higher and more stable accuracy, this study aimed to develop a method to computationally generate RCFs of herbal components. MATERIALS AND METHODS: This strategy included the published data collection, calibration curves screening, computer algorithm-based RCFs generation and accuracy validation. RESULTS: Using the in silico approach, we have successfully produced 133 RCFs for the multi-component quantitative analysis of 63 widely used herbs. CONCLUSION: Compared with conventional RCFs, this in silico method would be a low cost and highly efficient way to produce practical RCFs for the QAMS method.

Overexpression of Smad7 in hypothalamic POMC neurons disrupts glucose balance by attenuating central insulin signaling.

OBJECTIVE: Although the hypothalamus is crucial for peripheral metabolism control, the signals in specific neurons involved remain poorly understood. The aim of our current study was to explore the role of the hypothalamic gene mothers against decapentaplegic homolog 7 (Smad7) in peripheral glucose disorders. METHODS: We studied glucose metabolism in high-fat diet (HFD)-fed mice and middle-aged mice with Cre-mediated recombination causing 1) overexpression of Smad7 in hypothalamic proopiomelanocortin (POMC) neurons, 2) deletion of Smad7 in POMC neurons, and 3) overexpression of protein kinase B (AKT) in arcuate nucleus (ARC) in Smad7 overexpressed mice. Intracerebroventricular (ICV) cannulation of insulin was used to test the hypothalamic insulin sensitivity in the mice. Hypothalamic primary neurons were used to investigate the mechanism of Smad7 regulating hypothalamic insulin signaling. RESULTS: We found that Smad7 expression was increased in POMC neurons in the hypothalamic ARC of HFD-fed or middle-aged mice. Furthermore, overexpression of Smad7 in POMC neurons disrupted the glucose balance, and deletion of Smad7 in POMC neurons prevented diet- or age-induced glucose disorders, which was likely to be independent of changes in body weight or food intake. Moreover, the effect of Smad7 was reversed by overexpression of AKT in the ARC. Finally, Smad7 decreased AKT phosphorylation by activating protein phosphatase 1c in hypothalamic primary neurons. CONCLUSIONS: Our results demonstrated that an excess of central Smad7 in POMC neurons disrupts glucose balance by attenuating hypothalamic insulin signaling. In addition, we found that this regulation was mediated by the activity of protein phosphatase 1c.

Light-emitting diode photobiomodulation therapy for non-specific low back pain in working nurses: A single-center, double-blind, prospective, randomized controlled trial.

BACKGROUND: Low back pain (LBP) affects approximately 51% to 57% of hospital nurses and nurses' aides in Europe. New high-risk groups include home- and long-term-care nurses and physiotherapists. A number of European countries are experiencing a shortage of healthcare workers. Light therapy has been shown to be an effective treatment for various musculoskeletal disorders, including lateral epicondylitis, temporomandibular joint pain, carpal tunnel syndrome, and delayed-onset muscle soreness. A systematic review and meta-analysis demonstrated that low-level laser therapy is an effective method for relieving non-specific chronic low back pain (NSCLBP). However, the efficacy of light-emitting diode (LED) therapy for NSCLBP is disputed. This study aims to evaluate the effect of LED therapy on NSCLBP. METHODS AND ANALYSIS: We conducted a prospective, double-blind, randomized placebo-controlled trial of 148 patients with NSCLBP. The patients were randomly assigned to 2 groups: intervention group, where patients received LED photobiomodulation therapy 3 times a week for 2 weeks, and the sham group, where patients had sham therapy 3 times a week for 2 weeks. Primary outcome measures included the visual analog scale for pain, lumbar active range of motion assessments, and chair-rising times. Secondary outcome measures included a multidimensional fatigue inventory, fear-avoidance beliefs questionnaire, and the Oswestry disability index. The outcome measures were assessed before therapy and 2weeks, 4 weeks, 8 weeks, 12 weeks, and 6 months after the first interventions were completed. DISCUSSION: This study is a prospective, single-center, double-blind, randomized, controlled study. This study aims to research the efficacy of a 2-week LED program for NSCLBP working nurse. Our results will be useful for patients, working nurses, nurses' aides, and other healthcare workers with chronic low back pain. TRIAL REGISTRATION NUMBER: NCT04424823.

Picrasma quassioides Extract Elevates the Cervical Cancer Cell Apoptosis Through ROS-Mitochondrial Axis Activated p38 MAPK Signaling Pathway.

BACKGROUND/AIM: Picrasma quassioides (P. quassioides) is used in traditional Asian medicine widely for the treatment of anemopyretic cold, eczema, nausea, loss of appetite, diabetes mellitus, hypertension etc. In this study we aimed to understand the effect of P. quassioides ethanol extract on SiHa cervical cancer cell apoptosis. MATERIALS AND METHODS: The P. quassioides extract-induced apoptosis was analyzed using the MTT assay, fluorescence microscopy, flow cytometry and western blotting. RESULTS: P. quassioides extract induced cellular apoptosis by increasing the accumulation of cellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting ATP synthesis. Pretreatment with N-Acetylcysteine (NAC), a classic antioxidant, decreased the intracellular ROS production and inhibited apoptosis. In addition, the P38 MAPK signaling pathway is a key in the apoptosis of SiHa cells induced by the P. quassioides extract. CONCLUSION: The P. quassioides extract exerts its anti-cancer properties on SiHa cells through ROS-mitochondria axis and P38 MAPK signaling. Our data provide a new insight for P. quassioides as a therapeutic strategy for cervical cancer treatment.

Anti-tumor Properties of Picrasma quassioides Extracts in H-RasG12V Liver Cancer Are Mediated Through ROS-dependent Mitochondrial Dysfunction.

BACKGROUND: Picrasma quassioides (PQ) is a traditional Asian herbal medicine with anti-tumor properties that can inhibit the viability of HepG2 liver cancer cells. H-Ras is often mutated in liver cancer, however, the effect of PQ treatment on H-Ras mutated liver cancer is unclear. This study aimed to investigate the role of PQ on ROS accumulation and mitochondrial dysfunction in H-ras mutated HepG2 (HepG2G12V) cells. MATERIALS AND METHODS: PQ ethanol extract-induced HepG2G12V apoptosis was analyzed by the MTT assay, fluorescence microscopy, flow cytometry and western blotting. RESULTS: PQ treatment affected cell migration and colony formation in HepG2G12V cells. Cleaved-caspase-3, cleaved-caspase-9 and BCL2 associated agonist of cell death (BAD) expression levels were increased, while the levels of B-cell lymphoma-extra large (Bcl-xL) were decreased with PQ treatment. PQ treatment led to a reduction of H-Ras expression levels in liver cancer cells, thus reducing their abnormal proliferation. Furthermore, it led to increased expression levels of Peroxiredoxin VI, which regulates the redox signal in cells. CONCLUSION: Taken together these results provide a new functional significance for the role of PQ in treating HepG2G12V liver cancer.

Effect of a short-term vitamin E supplementation on oxidative stress in infertile PCOS women under ovulation induction: a retrospective cohort study.

BACKGROUND: Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown. METHODS: This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively. RESULTS: It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05). CONCLUSIONS: A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle. TRIAL REGISTRATION: ChiCTR-OOC-14005389, 2014.

Brief study on processing characteristics of first batch of classical prescriptions and suggestions on textual research / 中国中药杂志

As an important treasure for the research and development of new Chinese medicines, the classical prescriptions have a long medical history in China and are the summary of the clinical experience of the medical experts in the past dynasties. To support the research and development of classical prescriptions,relevant encouraging policies were issued by the state and relevant administrative departments. It is one of the key problems in the development process of classical prescriptions to verify and determine the processing methods of prescription herbal drugs. At present, there is no consensus or standard on such problems of classical prescriptions. In this paper, we sorted out and analyzed the related content of the herb processing for classical prescriptions, summarized the characteristics of the processing methods in the Catalogue of classical prescriptions(First Batch) and the problems faced in the textual research, and put forward some suggestions on the processing and textual research, including four research strategies: sorting out the mainstream methods for herbs in various periods of classical prescriptions, clarifying histological changes in the processing methods, determining the processing methods based on the drug processing characteristics, determining the processing methods based on the processing functions and identifying the processing methods according to the clinical efficacy and indication, so as to provide ideas and references for the research of processing methods involved in classical prescriptions.

[Brief study on processing characteristics of first batch of classical prescriptions and suggestions on textual research].

As an important treasure for the research and development of new Chinese medicines, the classical prescriptions have a long medical history in China and are the summary of the clinical experience of the medical experts in the past dynasties. To support the research and development of classical prescriptions,relevant encouraging policies were issued by the state and relevant administrative departments. It is one of the key problems in the development process of classical prescriptions to verify and determine the processing methods of prescription herbal drugs. At present, there is no consensus or standard on such problems of classical prescriptions. In this paper, we sorted out and analyzed the related content of the herb processing for classical prescriptions, summarized the characteristics of the processing methods in the Catalogue of classical prescriptions(First Batch) and the problems faced in the textual research, and put forward some suggestions on the processing and textual research, including four research strategies: sorting out the mainstream methods for herbs in various periods of classical prescriptions, clarifying histological changes in the processing methods, determining the processing methods based on the drug processing characteristics, determining the processing methods based on the processing functions and identifying the processing methods according to the clinical efficacy and indication, so as to provide ideas and references for the research of processing methods involved in classical prescriptions.

Integrating chemical similarity and bioequivalence: A pilot study on quality consistency evaluation of dispensing granule and traditional decoction of Scutellariae Radix by a totality-of-the-evidence approach.

There is an increasing focus on the quality consistency evaluation of dispensing granule in traditional Chinese medicines (TCMs). According to the guideline from Chinese Pharmacopoeia Commission, the substantial equivalence of dispensing granule and traditional decoction should be determined, and the chromatographic fingerprint has been recommended as a comprehensive qualitative approach to assess the quality consistency between dispensing granule and traditional decoction. However, a high-degree chemical similarity does not equal a bioequivalence. Attempting to realize the quality evaluation by integrating chemical consistency and bioequivalence, we herein proposed a totality-of-the-evidence approach based on clustering analysis and equivalence evaluation taking the dispensing granule and traditional decoction of Scutellariae Radix (SR) as a typical case. Chemical fingerprints were developed by high performance liquid chromatography coupled with photodiode array detector and quadrupole time-of-flight mass spectrometry (HPLC-PDA/QTOF-MS). Subsequently, a feature selection strategy, integrated linear and nonlinear correlation analysis, was carried out to assess the correlation between chemical profiles and biological activities. Finally, quality consistency between the dispensing granule and the traditional decoction was determined by bioactive marker-guided hierarchical clustering analysis (HCA), k-means clustering method and bioequivalence evaluation. The available evidence suggested that not all the dispensing granule of SR were sufficiently similar to the traditional decoction. This study provides an applicable methodology for quality consistency evaluation of dispensing granule and traditional decoction in TCMs.