[Research ontherapeutics effect of extract of Ornithogalum caudatum on liver fibrosis].

Rat models of liver fibrosis were made by carbon tetrachloride, and the serum levels of AST, ALT, γ-GT, MDA, GSH-px, SOD were detected, serum markers of PCⅢ, IV-C, LN, HA were detected by ELISA method. HE and Masson staining were conducted in hepatic tissues to observe pathological variations. Collagen Ⅲ, TGF-ß, α-SMA, E-cadherin were detected by Western blot. The curative effect of the extract of Ornithogalum caudatum on rat liver fibrosis induced by CCl4was observed and the mechanism was discussed. The experiment results showed that the extract of O. caudatum (50, 150, 500 mg•kg⁻¹) obviously decreased the serum levels of AST, ALT, γ-GT, MDA, increased the serum levels of GSH-px, SOD, decreased the expression of serum markers of PCⅢ, IV-C, LN, HA, and improved the liver pathological variations of fibrotic rats. The experiment proved that the extract of O. caudatum could treat the liver fibrogenesis induced by CCl4 in rats. The positive medicine may inhibit accumulation of extracellular and activate hepatic stellate cell and epithelial-mesenchymal transition.

Revisiting the Koebner phenomenon: role of NGF and its receptor system in the pathogenesis of psoriasis.

Nerve growth factor (NGF) influences the key pathological events of psoriasis: keratinocyte proliferation, angiogenesis, and T-cell activation. We have systematically examined the kinetics of NGF expression, keratinocyte proliferation, and migration of T lymphocytes in the epidermis in Koebner-induced developing psoriatic plaques. In skin traumatized by the tape-stripping method (n = 12), a marked up-regulation of NGF in Koebner-positive lesions (n = 7) was observed 24 hours after trauma. Synthesis of NGF reached its maximum level in the 2nd week. Furthermore, cultured keratinocytes from nonlesional skin of psoriasis patients produced 10 times higher levels of NGF compared with keratinocytes from healthy individuals. To substantiate the in vivo effect of NGF secreted by keratinocytes in psoriatic plaques, we studied psoriatic plaques and normal human skin in a SCID-human skin xenograft model. The transplanted psoriatic plaques demonstrated marked proliferation of NGF-R (p75)-positive nerve fibers compared with only a few nerves in the transplanted normal human skin. Our results demonstrate that 1) in a developing psoriatic lesion, up-regulation of NGF together with keratinocyte proliferation are early events and precede epidermotropism of T lymphocytes; 2) keratinocytes in patients with psoriasis are primed to produce elevated levels of NGF; and 3) NGF synthesized by these keratinocytes is functionally active.

FR255734, a humanized, Fc-Silent, Anti-CD28 antibody, improves psoriasis in the SCID mouse-psoriasis xenograft model.

In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal injections of FR255734 at 10, 3, and 1-mg kg(-1) doses. Groups treated with doses of 10 and 3 mg kg(-1) had significant thinning of the epidermis and reduced HLA-DR-positive lymphocytic infiltrates. The length of the rete pegs changed from 415.2+/-59.6 to 231.4+/-40.4 microm (P<0.005) in the 10-mg kg(-1) group, and from 323.4+/-69.6 to 237.5+/-73.6 microm in the 3-mg kg(-1) group (P=0.002). Positive controls treated with CTLA4-Ig and cyclosporine had significant histological improvement, whereas plaques treated with saline and isotype controls (human and mouse IgG2) remained unchanged. In vitro studies have shown that FR255734 effectively blocked T-cell proliferation and proinflammatory cytokine production. These observations warrant studies to evaluate the efficacy of FR255734 in human autoimmune diseases.

[Evidence and mechanisms of fetal origins of adult diseases].

This review focuses on the fetal origins of adult disease hypothesis put forward by David Barker and his colleagues, recent advances in epidemiological studies and experimental research in this field. Barker Hypothesis states that environmental factors, particularly intrauterine nutrition, as indicated by birth weight, operate in early life to program the risks for adverse health outcomes in adult life. A large growing body of reports described the association between the early development and adult diseases, such as diabetes, hypertension, coronary heart disease, abnormal lipids metabolism, obesity and cancer, etc. Experimental studies show that the changes of some key genes' expression, caused by epigenetic modifications, lead to a permanent alteration of cellular proliferation and differentiation and finally the genesis in key tissues and organs. These results bring about the impairment in structures and functions and the increased susceptibility to chronic diseases in adult life. The hypothesis provides a new perspective for the prevention and therapy of chronic diseases.

[A neglected master on integrative medicine: Wei-Ju ZHU].

Through analyzing the academic ideas in Shanghan Zhinan written by Wei-Ju ZHU, a modern famous physician, it is pointed out that ZHU's achievement on integrative medicine has been overlooked. Taking the theory of syndrome differentiation of six channels from Shanghan Lun as an example, ZHU presumed that the essence of therapeutic theory of traditional Chinese medicine was to conform to or strengthen human body's self-healing and self-regulating abilities. Since Yangqi is the major force in the body to help heal disease when it occurred, ZHU often took measures to strengthen Yang first in treating disease and also was good at using hot-natured herbs, such as Radix aconiti lateralis preparata. ZHU's thoughts on integrative medicine were concerned with etiology, pathology and therapeutics. In addition, ZHU generalized the syndrome differentiation into the theory of five phases and eight principles, and made important contributions to the history of integrative medicine. His thinking will provide valuable revelation for clinical practice and modern research on traditional Chinese medicine.

Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science.

The reasons why the standards of evaluating Western medicine are not suitable for testing traditional Chinese medicine (TCM) are explicit in the therapeutic objective and principles of TCM. TCM aims to correct maladjustments and restore the self-regulatory ability of the body, and not to antagonize specific pathogenetic targets. Maladjustments in a disease can be classified into several 'patterns' according to TCM theory. Multiple diseases might share one 'pattern' and be treated by the same herbal formula whereas one disease might display several different 'patterns' and be treated by multiple formulae. These principles are supported by evidence that multi-system changes in one pattern can be modulated by a herbal formula. The approaches used in systems biology and pharmacogenetics are similar to the practices of TCM. I propose that a combined approach using specific parameters associated with modern medicine, the general condition of individuals, as outlined by TCM, and pattern stratification of diseases should be employed to re-evaluate herbal formulae.

Therapeutic wisdom in traditional Chinese medicine: A perspective from modern science.

Extract: Misunderstanding usually stems from ignorance. This is the case for comments directed at each other by western medicine and traditional Chinese medicine (TCM). Modern biomedical scientists insist that herbal remedies need quality control, rigorous clinical trials, and illumination of active ingredients and their action mechanisms. In fact, almost all ever-increasing number of research projects on herbal medicine are being conducted based on this belief. Researchers often disrespect those so-called unique, seemingly inaccessible and ridiculous theories in traditional medicine. While, in the eyes of TCM doctors, most published articles about TCM in Western medicine journals haven't felt TCM's "pulse" yet. They thought that such studies are also ridiculous to focus only on herbal drugs instead of the thinking which guides drug's usage. This is like studying Vincent van Gogh's paintbrush instead of his thoughts about art expression. TCM experts are disgruntled with the demand and rebuke from western medicine. They believe the real efficacy and toxicity of herbal agents will not be adequately demonstrated using the present evaluation paradigm for single chemical compounds, since TCM does not focus solely on the disease defined by specific pathological changes (e.g., the level of blood pressure or sugar, the identifying of tumor cells or microorganisms, etc.) but instead concentrates on the overall functional state of the patient. However, because of TCM's classic naming systems, they can not convey their notions effectively to the field of the mainstream medicine.

[Preliminary exploration on establishing a simulated model of acute and chronic after-qi-stagnation blood stasis by adrenaline injection].

OBJECTIVE: To testify the TCM theory on "qi-stagnation causes blood stasis" and explore the method of using adrenaline to establish an acute and chronic blood stasis animal model. METHODS: Wistar rats were divided into 5 groups, the blank group (un-modeled), the model group A (modeled with once subcutaneous injection of 0.1% adrenaline), the model group B (modeled with once a day of subcutaneous injection of 0.01% adrenalinei for consecutive seven days), the Salvia group (treated with salvia after modeling) and the Chuanxiong group (treated with Chuanxiong after modeling). The model was established by simulating the anger and anxious status to form acute and chronic blood stasis model respectively and the treatments of Salvia and Chuanxiong was used to testify the syndrome type. Hemorrheologic parameters of the rats were measured. RESULTS: Compared with that in the blank group, the low sheared rate of whole blood viscosity increased, and the RBC deformability and aggregation index raised in both model group A and B (P < 0.01 or P < 0.05). Compared with that in Group A, in the Salvia group, the in vitro thrombus lengthened (P < 0.01), with its dry weight, wet weight increased (P < 0.01) after treatment, but the above-mentioned parameters in the Chuanxiong group were not changed at all. CONCLUSION: One time large dosage and multiple times of small dosage adrenaline subcutaneous injection to simulate angry and anxious status could produce blood stasis animal model. This fact provides an experimental basis for "Qi stagnation causes blood stasis" theory in TCM.