Characteristics and Functional Differences of Intestinal Flora in Type 2 Diabetes Mellitus Patients with Dampness Heat Trapping Spleen Syndrome and Qi-Yin Deficiency Syndrome： An Analysis Based on High-throughput Sequencing Technology / 中国实验方剂学杂志

ObjectiveTo explore the structural characteristics and functional differences of intestinal flora in patients with type 2 diabetes mellitus （T2DM） of dampness heat trapping spleen（DHTS） syndrome and Qi-Yin deficiency（QYD） syndrome. MethodFrom June 2018 to January 2020，62 T2DM patients with DHTS syndrome and 60 with QYD syndrome were selected from Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Serum and fecal samples were collected to compare body mass index（BMI），glucose and lipid metabolism，fasting insulin （FINS） and fasting C-peptide （FCP） levels，and homeostasis model assessment of insulin resistance（HOMA-IR） of the two syndrome types. Fecal samples were extracted for DNA database construction，and 16S rDNA high-throughput sequencing was used to analyze and compare the intestinal flora and metabolic pathways. Result① The BMI，fasting plasma glucose（FPG），2-hour postprandial blood glucose （2 h PBG），total cholesterol（TC），triglyceride（TG），low density lipoprotein（LDL），FINS，FCP，and HOMA-IR were higher in patients with DHTS syndrome than in patients with QYD syndrome，and the high density lipoprotein（HDL） of the former was lower than that of the latter，（P<0.05，P<0.01）. ② In terms of species composition and differences，Bacteroidetes， Clostridia and Gammaproteobacteria were dominant at the class level，and the relative abundance of Clostridia，Mollicutes and Verrucomicrobiae in QYD syndrome group was higher than that in DHTS syndrome group. At the order level，Bacteroidales，Clostridiales and Enterobacteriales were mainly found. The relative abundance of Clostridiales，Erysipelotrichales and Verrucomicrobiales in QYD syndrome group was obviously higher than that in DHTS syndrome group，while Aeromonadales in the former was lower than that in the latter （P<0.05）. At the family level，Bacteroidaceae，Prevotellaceae and Ruminococcaceae were predominant. The relative abundance of Ruminococcaceae，Porphyromonadaceae and Erysipelotrichaceae in QYD syndrome group was higher than that in DHTS syndrome group（P<0.05）. At the genus level，Bacteroides，Prevotella and Parabacteroides were mainly found. The relative abundance of Parabacteroides，Butyrivibrio and Ruminiclostridium in QYD syndrome group was higher than that in DHTS syndrome group，while that of Klebsiella and Megasphaera in DHTS syndrome group was higher than that in QYD syndrome group（P<0.05）. ③ Through Venn analysis of operational taxonomic units（OTU），it was found that there were 49 OTUs in patients with DHTS syndrome patients and 47 OTUs in QYD syndrome patients. ④ The results of OTU β diversity and α analysis showed that Shannon and Simpson indexes had statistical differences，while Ace and Chao indexes had no statistical differences. The intestinal microbial diversity of patients with QYD syndrome was higher than that of patients with DHTS syndrome（P<0.05）. The analysis of similarities （ANOSIM） showed that the difference of β diversity between the two groups was significant（P<0.05）. ⑤ Linear discriminant analysis Effect Size（LEfSe） results demonstrated that Klebsiella，Megasphaera and Aeromonadales could be selected as the key biomarkers for DHTS syndrome； 14 bacteria such as Ruminiclostridium，Burkholderiaceae，Lautropia，Butyrivibrio，Erysipelotrichales can be selected as the key biomarkers for QYD syndrome. ⑥Functional annotation and analysis showed that the DHTS syndrome involved 9 metabolic pathways，including arginine and proline metabolism，lipopolysaccharide biosynthesis，nicotinic acid and nicotinamide metabolism，while the QYD syndrome involved 10 metabolic pathways，including acarbose and valinomycin biosynthesis，glucagon signaling pathway and NOD-like receptor signaling pathway. ConclusionThere are obvious differences in intestinal flora and functions in T2DM patients of DHTS syndrome and QYD syndrome，which can be used as reference for traditional Chinese medicine （TCM） syndrome differentiation and the target of TCM treatment.

Quantitative and Fingerprint of Ilex pubescens Slices / 中国实验方剂学杂志

Objective:To establish HPLC-UV fingerprints of Ilex pubescens pieces,and simultaneously determine two components in 46 batches of I. pubescens in pieces of I. pubescens saponin A1 and B1,in order to provide a reference for the quality standard of I. pubescens slices. Method:Methanol was used to extract the I. pubescens saponin samples,and the extracts were measured by HPLC-UV with the absorption wavelength at 210 nm. Kromasil C18 column (4.6 mm×250 mm,5 μm) was used for determining the extracts at a flow rate of 1.0 mL·min-1. The mobile phase condition was acetonitrile-0.1% phosphoric acid aqueous solution with gradient mode. The chromatographic fingerprint similarity evaluation system of traditional Chinese medicine (2012 edition) was used to analyze I. pubescens fingerprints. SPSS 20.0 software was used to cluster the peak area of common peaks. Principal component analysis was performed to reduce the dimension of common peaks. Result:There were great differences between the root and stem parts in I. pubescens fingerprints. The fingerprints of roots and stems of I. pubescens were established respectively,cluster results assorted the roots of I. pubescens into three categories andthe branches of I. pubescens into two categories. The integrity and difference of I. pubescens decoction pieces from different parts and places of origin were compared,and the principal component analysis was performed to screen out the common components that played a decisive role in fingerprint of I. pubescens pieces. And the common peaks were determined. The content of saponin A1 and saponin B1 in Radix I. pubescens were determined. Conclusion:The established I. pubescens fingerprints and content determination methods are simple and suitable. Cluster analysis and principal component analysis are used to screen out the key components of quality control of I. pubescens. The results can provide references for quality control of I. pubescens.

Research progress of 5-hydroxymethylfurfural, a safety-related substance in traditional Chinese medicine injections / 中国中药杂志

Screening out the safety-related substances and establishing the corresponding standard has been a key research issue to improve the safety of traditional Chinese medicine injections(TCMIs). 5-HMF which widely exists in sugar-containing TCMIs has long been considered as an important safety-related substance. In this review, we summarizes the research progress on the toxicology of 5-HMF as well as the content and standards of 5-HMF in TCMIs.Therein, both literature summary and analysis results indicate that there are lack of toxicology researches of 5-HMF and its metabolites in TCMIs, although the potential toxicity of 5-HMF and its metabolites has been reported. Moreover, the content of 5-HMF largely varies from TCMIs to TCMIs, and even in the same TCMIs from different factories. To ensure the clinical efficacy of TCMIs, it urgent to carry out the study of the toxicology of 5-HMF in TCMIs comprehensively and systematically, so as to set up a relatively uniform standard as well as to develop process quality control method.

Pharmacokinetic-Pharmacodynamic Analysis on Inflammation Rat Model after Oral Administration of Huang Lian Jie Du Decoction.

Huang-Lian-Jie-Du Decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK) and pharmacodynamic (PD) data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR) of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM) method. Additionally, the levels of 7 cytokines (CKs) in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax) and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, IL-10, and macrophage inflammatory protein-2 (MIP-2) and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that HLJDD may restrain inflammation synergistically via its major constituents (alkaloids, flavonoids and iridoids). A correlation between the exposure concentration of different types of compounds and their anti-inflammatory effects in the body was shown. This study provides a comprehensive understanding of the anti-inflammatory activity of HLJDD.

[Chemical studieson hydrophilic constituents of toad skin].

Fifteen compounds were isolated from the toad skin by a combination of various chromatographic methods including macroporous resin, silica gel, ODS and semi-preparative HPLC. Their structures were identified as 4,5-dimethyl-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-6-ol(1), serotonin(2), N-methyl serotonin(3), O-methyl bufotenine(4), 1,2,3,4-tetrahydro-6-hydroxy-ß-carboline(5), O-methylserotonin(6), glycinebetaine(7), caffeine(8), bufotenine(9), shepherdine(10), tryptophan(11), (5-hydroxy-1H-indol-3-yl)acetic acid(12), 5-hydroxy tryptophol(13), 2-methyl-6-hydroxy-1,2,3,4-tetrahydro-ß-carboline(14), bufothionine(15). Among them, compound 1 was a new compound,compound 5 was a new natural product. Compounds 4-8 and 10-14 were separated from toad skin for the first time.

Randomized Clinical Trial Comparing Efficacy of Simo Decoction and Acupuncture or Chewing Gum Alone on Postoperative Ileus in Patients With Hepatocellular Carcinoma After Hepatectomy.

To compare the efficacy of simo decoction (SMD) combined with acupuncture at the tsusanli acupoint or chewing gum alone for treating postoperative ileus in patients with hepatocellular carcinoma (HCC) after hepatectomy.In postoperative ileus, a frequent complication following hepatectomy, bowel function recovery is delayed, which increases length of hospital stay. Studies suggest that chewing gum may reduce postoperative ileus; SMD and acupuncture at the tsusanli acupoint have long been used in China to promote bowel movement.Patients with primary HCC undergoing hepatectomy between January 2015 and August 2015 were randomized to receive SMD and acupuncture (n = 55) or chewing gum (n = 53) or no intervention (n = 54) starting on postoperative day 1 and continuing for 6 consecutive days or until flatus. Primary endpoints were occurrence of postoperative ileus and length of hospital stay; secondary endpoints were surgical complications.Groups treated with SMD and acupuncture or with chewing gum experienced significantly shorter time to first peristalsis, flatus, and defecation than the no-intervention group (all P < 0.05). Hospital stay was significantly shorter in the combined SMD and acupuncture group (mean 14.0 d, SD 4.9) than in the no-intervention group (mean 16.5 d, SD 6.8; P = 0.014), while length of stay was similar between the chewing gum group (mean 14.7, SD 6.2) and the no-intervention group (P = 0.147). Incidence of grades I and II complications was slightly lower in both intervention groups than in the no-intervention group.The combination of SMD and acupuncture may reduce incidence of postoperative ileus and shorten hospital stay in HCC patients after hepatectomy. Chewing gum may also reduce incidence of ileus but does not appear to affect hospital stay. (Clinicaltrials.gov registration number: NCT02438436.).

Evaluation of the conjoint efficacy in Chinese medicine with the longitudinal latent variable linear mixed model / 中国结合医学杂志

Chinese medicine (CM) clinical efficacy evaluation research involves the longitudinal multivariate measurement which means that patients are measured repeatedly and each patient is measured by several indicators on each fixed cross-section. Although each indicator can be evaluated separately with a longitudinal linear mixed model, it is important to consider all the endpoints together especially when researchers pay special attention to the change of the conjoint efficacy for several indicators in one patient. In this article, we introduce a latent variable linear mixed model to the CM conjoint efficacy evaluation and discuss why and how to analyze the longitudinal multivariate endpoint data in the clinical CM efficacy evaluation research. It may lead to the new insight of using such methodology in the field of conjoint efficacy evaluating of CM study. And with the definition of syndrome and symptom in the CM theory, the applied discussion brings the insight of CM syndrome evaluating in future. We illustrate this methodology using an example of CM efficacy evaluation from an ischemic stroke research.

English translation of the title of ancient Chinese medical books and documents / 中国中西医结合杂志

The title of a book is, generally, the high concentration of the writer's intention and the theme of content. Translate the title of an ancient Chinese medical book or document accurately and plainly is meaningful for exhibiting the style of the book, also for promoting the international communication of TCM. The principle should be followed is to choose the translating terms accurately to reveal the theme of content and express the cultural connotation of the book perfectly.