Serum metabolomics analysis of biomarkers and metabolic pathways in patients with colorectal cancer associated with spleen-deficiency and qi-stagnation syndrome or damp-heat syndrome: a prospective cohort study.

Objective: To profile the serum metabolites and metabolic pathways in colorectal cancer (CRC) patients associated with spleen-deficiency and qi-stagnation syndrome (SDQSS) or damp-heat syndrome (DHS). Methods: From May 2020 to January 2021, CRC patients diagnosed with traditional Chinese medicine (TCM) syndromes of SDQSS or DHS were enrolled. The clinicopathological data of the SDQSS and DHS groups were compared. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). The variable importance in the projection >1, fold change ≥3 or ≤0.333, and P value ≤0.05 were used to identify differential metabolites between the two groups. Furthermore, areas under the receiver operating characteristic (ROC) curve > 0.9 were applied to select biomarkers with good predictive performance. The enrichment metabolic pathways were searched through the database of Kyoto Encyclopedia of Genes and Genomes. Results: 60 CRC patients were included (30 SDQSS and 30 DHS). The level of alanine aminotransferase was marginally significantly higher in the DHS group than the SDQSS group (P = 0.051). The other baseline clinicopathological characteristics were all comparable between the two groups. 23 differential serum metabolites were identified, among which 16 were significantly up-regulated and 7 were significantly down-regulated in the SDQSS group compared with the DHS group. ROC curve analysis showed that (S)-3-methyl-2-oxopentanoic acid, neocembrene, 1-aminocyclopropanecarboxylic acid, 3-methyl-3-hydroxypentanedioate, and nicotine were symbolic differential metabolites with higher predictive power. The top five enrichment signalling pathways were valine, leucine and isoleucine biosynthesis; lysosome; nicotine addiction; fructose and mannose metabolism; and pertussis. Conclusion: Our study identifies the differential metabolites and characteristic metabolic pathways among CRC patients with SDQSS or DHS, offering the possibility of accurate and objective syndrome differentiation and TCM treatment for CRC patients.

[Expression of CD44v6 and COX-2 in pleomorphic adenomas and carcinomas of parotid gland].

PURPOSE: To investigate the correlation between CD44v6 and cyclooxygenase-2(COX-2) expression and recurrence and deterioration of pleomorphic adenoma of parotid gland. METHODS: Immunohistochemistry was used to detect the expression of CD44v6 and COX-2 in 19 normal parotid tissues, 25 primary pleomorphic adenomas, 15 first recurrent pleomorphic adenoma, 15 second recurrent pleomorphic adenoma and 13 cancer in pleomorphic adenomas. The correlation between CD44v6 and COX-2 and the recurrence and deterioration of pleomorphic adenomas was evaluated using SPSS 15.0 software package. RESULTS: The positive expression rate of CD44v6 in normal parotid gland, primary pleomorphic adenoma, first recurrent pleomorphic adenoma, second recurrent pleomorphic adenoma and cancer was 5.26%, 44.00%, 60.00%, 93.37% and 100.00%, respectively;and the positive expression rate of COX-2 was 10.53%, 40.00%, 63.33%, 93.37% and 100.00%, respectively. There was significant difference in the positive expression intensity of CD44v6 and COX-2 among the groups (P<0.05). The positive expression rate and intensity of CD44v6 and COX-2 in normal parotid gland tissue were significantly lower than those in other groups (P<0.05). There was no significant difference in the positive expression rate and intensity of CD44v6 between primary pleomorphic adenoma and first recurrent pleomorphic adenoma (P>0.05). There was no significant difference in the expression intensity of COX-2 between the two groups (P>0.05), but the positive expression rate of COX-2 between the two groups was not significant(P>0.05). The positive expression rate and intensity of CD44v6 and COX-2 in the second recurrent pleomorphic adenoma were significantly higher than those in the first recurrent pleomorphic adenoma(P<0.05), but there was no significant difference between the two groups(P>0.05). CD44v6 in the second recurrent pleomorphic adenoma and cancer was significantly higher than that in the first recurrent pleomorphic adenoma(P<0.05). There was no significant difference in the expression rate and intensity of COX-2 (P>0.05). CONCLUSIONS: CD44v6 and COX-2 may play an important role in promoting occurrence, invasion, recurrence and deterioration of pleomorphic adenoma through synergistic action.

TVT versus TOT in the treatment of female stress urinary incontinence: a systematic review and meta-analysis.

BACKGROUND: To evaluate the evidence available on the effects and safety of tension-free vaginal tape (TVT) versus transobturator tape (TOT) for female stress urinary incontinence therapy based on randomized controlled trials (RCTs). METHODS: PubMed, Cochrane, Embase, Wanfang, China National Knowledge Infrastructure, and Weipu database were searched up to July 2017 to identify relevant studies, including qualified RCT and quite-RCT and literature sources. Relative risks (RRs), mean difference (MD), and 95% CI were calculated in our review. RESULT: Twenty-eight RCTs were involved in the meta-analysis with 2,505 patients in the TVT group and 2,477 patients in the TOT group. The aggregated results indicated that TOT significantly decreased the operative time (MD, -1.27; 95% CI: -1.77 to -0.76) and hospital stay (MD, -0.62; 95% CI: -1.08 to -0.17) when compared with TVT. Besides, the complications (RR, 0.86; 95% CI: 0.64-1.16) and blood loss (MD, -0.29; 95% CI: -0.71 to 0.14) were decreased in TOT but with no statistical significance; the change of VAS score (MD, 0.07; 95% CI: -0.05 to 0.19), IIQ-7 score (MD, 0.06; 95% CI: -0.03 to 0.15), and UDI-6 score (MD, 0.15; 95% CI: -0.19 to 0.48) were larger in TOT group than in TVT group, but still, with no statistical significance. However, there was no significant difference of cure rate (RR, 1.00; 95% CI: 0.96-1.04) and satisfied rate (RR, 1.00; 95% CI: 0.96-1.04) between the 2 groups. CONCLUSION: TOT may have more valid effects than TVT in operative time and hospital stay. Besides, TOT method showed fewer complications and blood loss than TVT, but there was no significant difference between them. The scores of VAS, incontinence impact questionnaire short form-7 (IIQ-7), and urogenital distress inventory short form-6 (UDI-6) were higher in TOT than TVT, but still no significant difference was observed. However, more studies with higher quality and larger sample size that are multicentric and have longer follow-up in the form of RCTs are warranted to confirm the current findings.

Molecular cloning and functional analysis of a 10-epi-junenol synthase from Inula hupehensis.

Junenol based-eudesmanolides have been detected in many compositae plant species and were reported to exhibit various pharmacological activities. So far, the gene encoding junenol synthase has never been isolated. Here we report the molecular cloning and functional analysis of a 10-epi-junenol synthase from Inula hupehensis (designated IhsTPS1). IhsTPS1 converts the substrate farnesyl diphosphate into multiple sesquiterpenes with the product 10-epi-junenol being predominant. The transcript levels of IhsTPS1 correlate well with the accumulation pattern of 10-epi-junenol in I. hupehensis organs, supporting its biochemical roles in vivo.

Molecular cloning and functional characterization of two divergent 4-coumarate†:†coenzyme A ligases from Kudzu (Pueraria lobata).

As part of the efforts to understand isoflavonoid metabolism in Pueraria lobata at the molecular level, the cDNAs encoding two divergent 4-coumarate : coenzyme A ligases (4CLs, designated Pl4CL1 and Pl4CL2, respectively) were isolated from P. lobata roots. Sequence analysis revealed that Pl4CL1 had an N-terminal extension of twenty-one amino acid residues compared to Pl4CL2. Phylogenetic analysis showed that Pl4CL1 and Pl4CL2 fell into angiosperm Class II and Class I, respectively. Through in vitro biochemical assays, both Pl4CLs were found to have the capacity to utilize 4-coumarate and trans-cinnamate as substrates, while neither of them could convert sinapate. Pl4CL2 had a broader substrate specificity than Pl4CL1. The affinity of Pl4CL1 for 4-coumarate was 2.6-fold higher than that of Pl4CL2 (with the Km values of 3.5 µM and 9.1 µM, respectively). Combining the dataset including gene expression profiles, metabolites measurements, and biochemical properties, our results indicated that Pl4CL1, just as other angiosperm Class II 4CLs, might play a role in isoflavone biosynthesis in P. lobata, while Pl4CL2 belongs to angiosperm Class I, and may function as a housekeeping enzyme concerning lignification.

[Study protocol for a self-controlled case study to evaluate the safety and standardization for external application of Chinese medicine Jiuyi Powder].

BACKGROUND: As the main medicinal powder for drawing out pus and removing necrotic tissue in external therapies of traditional Chinese surgery, Sheng Powder has made great contributions to the treatment of inflammatory wounds and has the unique bactericidal and decay-discharging function that can not be replaced by antibiotics. However, Sheng Powder has toxicity because it contains mercury. So far, there is no clinical research on the standards of dose and usage of Sheng Powder and there is a lack of objective and quantitative criteria for operating standards and monitoring of toxicity and side effects. Therefore, the authors choose Jiuyi Powder, one of the most commonly used Sheng Powder, to evaluate the safety of its external use, and form a standardization program for clinical implementation. METHODS AND DESIGN: This study is a nonrandomized, nonblinded, self-controlled case study. There will be two key stages in the study. In stage one, 10 patients with plasma cell mastitis will be enrolled. The patients will receive continuous external application of Jiuyi Powder with a fixed dose (160 mg/d). Blood mercury and urine mercury levels will be dynamically tested at different time intervals, and the observation of pharmacokinetic parameters will be conducted after Jiuyi Powder has been absorbed by the surface of the wound. In stage two, 30 patients with each of the four conditions including postoperative wounds of head or facial surgeries, plasma cell mastitis, anal fistula and chronic absorption ulcer of the shank will be enrolled, respectively. According to the dose of 1.5 mg/cm(2), Jiuyi Powder will be externally applied to the wound surface for 14 d. On the basis of the first-phase study, the test time will be chosen and the toxicity outcome will be detected to evaluate the safety of external application of Jiuyi Powder and to establish recommendations for standardized clinical use. DISCUSSION: The purpose of this study is to evaluate the safety of the external application of Jiuyi Powder through a two-stage study. The pharmacokinetic parameters of external application of Jiuyi Powder at the clinical dose range, the changes in blood and urinary mercury levels and related safety indexes will be observed on different wounds located in different positions externally. The evaluation of whether Jiuyi Powder could be a routine medication for drawing out pus and removing necrotic tissue in inflammatory and refractory wounds will be stated. TRIAL REGISTRATION NUMBER: ChiCTR-TNC-11001366.

Cloning and functional characterization of a chalcone isomerase from Trigonella foenum-graecum L.

Flavonoids belong to a group of plant natural products with variable phenolic structures and play important roles in protection against biotic and abiotic stress. Fenugreek (Trigonella foenum-graecum L.) seeds and stems contain flavonol glycosides and isoflavone derivatives. Up to now, the molecular features of fenugreek flavonoid biosynthesis have not been characterized. Here we present cloning of a cDNA encoding a chalcone isomerase (namely TFGCHI-1) from the leaves of T. foenum-graecum which convert chalcones to flavanones in vitro. Transformation of Arabidopsis loss-of-function TT5 (CHI) mutant with a TFGCHI-1 cDNA complemented TT5 and produced higher levels of flavonol glycosides than wild-type Col-0.

Isolation and characterization of a new ginsenoside from the fresh root of Panax Ginseng.

A new saponin, malonylginsenoside Ra3, was isolated from the fresh root of Panax ginseng, along with four known ginsenosides. The new compound was identified as (20S)-protopanaxadiol-3-O-(6-O-malonyl-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranoside-20-O-beta-D-xylopyranosyl(1-->3)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis.

A new geldanamycin analogue from Streptomyces hygroscopicus.

A new geldanamycin analogue was isolated from Streptomyces hygroscopicus A070101. The structure was elucidated as 11-methoxy-17-formyl-17-demethoxy-18-O-21-O-dihydrogeldanamycin (1) on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. Compound 1 showed considerable cytotoxicity (SRB) against human cancer cell lines (breast cancer MCF-7, skin melanoma SK-MEL-2 and lung carcinoma COR-L23).