In traditional Chinese medicine(TCM),abnormal and diseased conditions have been defined as Zheng Hou, a unique disease definition system in the context of holism. For over 3000 years the main clinical treatment method for TCM therapeutics has been so called Fang-ji, a TCM medicinal formula usually composed of several herbs and medical materials. The compositions of Fang-ji are based on the clinical practice under the guidelines of "bian-zheng-lun-zhi" and the principles of "Jun-chen-zuo-shi". Each Zheng is treated with a correspondingly-individualized Fang-ji.The modern approach to the study of Fang-ji pharmacology,however,has been focusing on the isolation and identification of individual active components for cellular and molecular targets. Although this approach has led to the development of many new monomers purified from Fang-ji as new drugs widely used in clinical practice such as the an-timalarial artemsinin,which has earned a Nobel Prize,the pharmacological bases of these purified effective monomers or active components have lost the TCM characteristics and are far different from the phar-macological theory and clinical applications of Fang-ji,in terms of the principles of"bian-zheng-lun-zhi"and "Jun-chen-zuo-shi". Here we introduce the emerging pharmacophenophenics as a systematical paradigm for the pharmacological study of Fang-ji.Pharmacophenomics studies the orchestrated multi-target pharmacology of combination therapy.With well-defined molecular mechanisms of Zheng Hou at the level of multi-omics and a suite of new phenomics technologies and platforms, the pharmacophe-nomics may be used to characterize the drug-response phenome of Fang-ji and to identify the corre-sponding multiple therapeutic targets according to the TCM theory of Jun-chen-zuo-shi.Pharmacophe-nomic study of Fang-ji will also lay a theoretical foundation for the new science of precision medicine.

A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.
Adenoma ; Animals ; Bacteria ; Bacteroides fragilis ; Carcinogenesis* ; Colon ; Colorectal Neoplasms ; Enterotoxins ; Escherichia coli ; Fecal Microbiota Transplantation ; Fusobacterium nucleatum ; Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Mice ; Microbiota* ; Models, Theoretical* ; Mutagens ; Rats ; Virulence ; Virulence Factors

The present study was performed to observe histopathological effects of Oculotrema hippopotami Stunkard, 1924 infection in the eye of Hippopotamus amphibius, as well as to reveal new details of morphology and structural features of this monogenean and its comparison between 2 age stages of the parasite. This was done using both light and scanning electron microscopy, energy dispersive X-ray analysis (EDXA) and histopathology. The presence of a mixture of different generations (adult and sub-adult) in one host individual is common for Oculotrema Stunkard, 1924 in contrast to Polystoma Zeder, 1800. New metrical and graphical information obtained for adults and sub-adults compared with the previous studies. Here we show the presence of genital papillae in adults, metrical data on the distal part of the vas deferens. SEM micrographs of sperm ejaculatory structures and information about the flattened dorsal side of the body provided for the first time. Histopathological changes, such as necrosis and hemorrhage in host tissues as a result of O. hippopotami attachment structures are described. Structural analysis of different body parts of O. hippopotami of both age groups are also included. We show qualitative differences in the presence of hardening ions (S, P, Ca) in attachment structures (oral and haptor suckers) that increase with the age of the worm. The presence of sub-adults and adults on the same host, together with high levels of infection without high pathogenicity may account for Oculotrema being one of the most successful parasites among the Monogenea.
Adult ; Family Characteristics ; Hemorrhage ; Human Body ; Humans ; Ions ; Microscopy, Electron, Scanning ; Necrosis ; Parasites ; Spermatozoa ; Vas Deferens ; Virulence

Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis(TM), we identified genes (up- or down-regulated, > or = 1.5 fold, P < or = 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 microg/ml) in UtLM cells. Downregulation of TGF-beta signaling pathway genes, activin A, activin B, Smad3, TGF-beta2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-beta pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.
Activins/*genetics/metabolism/pharmacology ; Anticarcinogenic Agents/*pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cyclin-Dependent Kinase Inhibitor p15/genetics/metabolism ; Down-Regulation ; Female ; Genistein/*pharmacology ; Humans ; Leiomyoma/*metabolism ; Oligonucleotide Array Sequence Analysis ; Signal Transduction/drug effects ; Smad3 Protein/*genetics/metabolism ; Transforming Growth Factor beta/*genetics/metabolism ; Up-Regulation ; Uterine Neoplasms/*metabolism

BACKGROUND: Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce the patient's steroid dose and maintain low disease activity in systemic lupus erythematosus (SLE). OBJECTIVE: This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE. SEARCH STRATEGY: A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included "systemic lupus erythematosus," "Chinese medicine" and "clinical trial," and their synonyms. Subject headings matching the above terms were also used. INCLUSION CRITERIA: This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids. DATA EXTRACTION AND ANALYSIS: Two authors independently conducted database search, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI). RESULTS: In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58-5.01; P < 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects. CONCLUSION The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH's relevant bioactive constituents.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome