In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.
Biomedical Research ; China ; Clinical Trials as Topic ; Databases, Factual ; Humans ; Medicine, Chinese Traditional ; United States

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.
Biomarkers ; blood ; urine ; Chemical and Drug Induced Liver Injury ; diagnosis ; Humans ; Sensitivity and Specificity

Acquired Immunodeficiency Syndrome ; epidemiology ; prevention & control ; HIV Infections ; epidemiology ; prevention & control ; Humans ; Population Surveillance ; methods

International clinical trials register is one of the global measures to realize transparency in clinical trials and also one of a powerful measure to improve the quality of clinical trials. Many scholars studying the quality of TCM clinical trials find that they are poor in quality and lack transparency. Furthermore, they find that TCM clinical trial registry has many problems. We must base on the successful experiences of WHO and international clinical trial registry to establish technical specifications for registry of traditional Chinese medicine clinical study of their own. Then, it can effectively improve the overall level of TCM clinical studies. We have suggested some concrete and feasible measures to establish technical specifications for registry of traditional Chinese medicine clinical study of their own based on the problems of TCM clinical trial registry.
Biomedical Research ; Humans ; Medicine, Chinese Traditional ; standards ; Registries

In temporomandibular disorders (TMD), pain takes place when neuropeptides stimulate synovial tissue to produce several cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, which activate neurons and glia of synovial membrane at the bilaminar regions of temporomandibular joint (TMJ). It has been reported that, after neurogenic differentiation, the synovial mesenchymal stem cells (SMSCs), deriving from TMJ, possess the same cytological features as the neuronal cells. This study examined the ability of substance P (SP) and calcitonin gene-related peptide (CGRP) to stimulate SMSCs and neurogenic SMSCs secreting inflammatory cytokines during TMD, evaluated the mutual effects of inflammatory cytokines and neuropeptides and tested the analgesic effect of hyaluronic acid (HA). The levels of IL-1β, IL-6 and TNF-α in SMSCs and neurogenic SMSCs in the presence of neuropeptides were measured by ELISA. SP and CGRP produced by SMSCs and neurogenic SMSCs were determined by RT-PCR and Western blotting. The results showed that the expression of SP and CGRP was significantly enhanced in the neurogenic SMSCs in response to IL-1β, IL-6 and TNF-α, and the effect was remarkably inhibited by HA. IL-1β, IL-6 and TNF-α, in return, could be enhanced in the neurogenic SMSCs upon stimulation by SP and CGRP. Neuropeptides and inflammatory cytokines might work mutually on the TMD pain. The HA-mediated analgesic effect may be implicated in the inhibition of SP and CGRP expression in neurogenic SMSCs.

A phytochemical investigation on the aerial parts of a Tibetan medicine Meconopsis horridula, by solvent extraction, repeated chromatographies on silica gel, Sephadex LH-20, and preparative TLC techniques, led to the isolation of 9 compounds. By spectroscopic analysis and comparison of its 1H and 13C-NMR data with those in literatures, their structures were identified as oleracein E(1), N-( trans-p-coumaroyl) tyramine (2), chrysoeriol (3), apigenin (4), hydnocarpin (5), p-coumaric acid glucosyl ester (6), stigmast-5-ene-3beta-ylformate (7), 3beta-hydroxy-7alpha-ethoxy-24beta-ethylcholest-5-ene (8), and beta-sitosterol (9), respectively, among which compounds 6-8 were isolated from the genus for the first time,and 1,3 were isolated from the species for the first time. A MTT method was applied to evaluate the cytotoxic activity of compounds 14 against the human hepatocellular liver carcinoma cell line (HepG2), and compound 1 showed significant cytotoxicity against HepG2,with its inhibitory rate of 52.2% at 10 micromol x L(-1).
Medicine, Tibetan Traditional ; Molecular Structure ; Papaveraceae ; chemistry ; Plant Extracts ; chemistry ; Spectrometry, Mass, Electrospray Ionization

Litsea cubeba is one of aromatic medicinal plant belonging to family Lauraceae. The roots, stems and fruits of L. cubeba have been widely applied as folk medicines in some districts in China for relieving rheumatism and cold, regulating Qi (meridian) to alleviate pain. Previous studies revealed that this species contains major alkaloids, in specific aporphines, and minor flavonoids, lignans as well. Related pharmacological investigations demonstrated its activities and clinical applications on cardiovascular diseases, anti-cancer, against rheumatoid arthritis, relieving asthma and anti-allergic effects, as anti-oxidants, and so on. As an effort for further exploration of this bioactive ingredients and potential drug development, this paper summarizes most phytochemical and pharmacological results. Further, future prospects are also included.
Animals ; Drug Therapy ; Humans ; Litsea ; chemistry ; Molecular Structure ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry

Objective To characterize the clinical manifestations, laboratory findings of patients with occult sys?temic malignant neoplasms, whose initial manifestation presented as multiple acute cerebral infarcts including coagula?tion function,radiological imaging and microembolic signals (MES) detection by transcranial Doppler sonography (TCD) and to explore the possible underlying mechanisms. Methods All clinical records, laboratory hematological tests includ?ing hypercoagulable states measured by D-dimer levels, brain MRI including DWI, and TCD monitoring MES, the treat?ment and prognosis were retrospectively reviewed in 12 patients with multiple acute cerebral infarcts as the first manifes?tation of occult systemic malignancy. Results The clinical manifestations presented as localized neurological dysfunction, e.g. hemiparesis, aphasia, hemiparesthesia, dysarthria, vertigo and seizures, etc. DWI revealed multiple disseminated acute cerebral infarcts in multiple arterial territories such as the bilateral anterior or anterior plus posterior cerebral circu?lation in all patients. Eleven of 12 patients tested had elevated D-dimer. TCD detected MES in 5 of 7 patients. There were 12 patients diagnosed with occult systemic malignancy including 5 lung cancer, 3 pancreatic cancer, 1 gastric can?cer, 1 colon cancer, 1 endometrial adenocarcinoma and 1 metastatic poorly differentiated mucinous adenocarcinoma with unknown primary. Ten patients already had remote metastasis at diagnosis. The prognosis was usually poor and there were 7 cases with ischemic stroke recurrence, 4 cases with acute myocardial infarction, 3 cases died during hospitaliza?tion. Conclusions When patients present with multiple disseminated acute cerebral infarcts involving multiple arterial territories as initial manifestation, the underlying occult systemic malignancy should be considered. Hypercoagulopathy and MES might provide the clues to the diagnosis.

BACKGROUND:The intestine is not only the main target attacked by sepsis but also the vital organ which mediated sepsis. The recovery of the damaged intestinal barrier structure and function is related to the occurrence and outcome of multiple organ dysfunction syndrome (MODS). How to protect and reduce the damage of the intestinal mucosa and how to promote the reconstruction of the intestinal mucosa have been the important topics in sepsis for many years. This study aimed to investigate the influential factors of intestinal mucosal reconstruction after intestinal epithelial injuryin vivo in a mouse model of sepsis.METHODS:Mice were subjected to cecal ligation and puncture (CLP) for induction of sepsis to assess intestinal mucosal damage, epithelial cell apoptosis, and transformed number of goblet cells, and to detect the concentration of TNF-α, IL-1 and TGF-β1 and TFF3 (trefoil factor 3) expression in the small intestinal mucosa. All above were performed by HE staining, western blot, ELISA and immunohistochemistry respectively. The experimental animals were divided into a sepsis group and a sham-operation group. The animals with sepsis were separately killed at 6 (7 animals), 24 (7 animals) and 48 hours (7 animals) after CLP.RESULTS:Injured intestinal mucosa was observed in the 3 groups under a light microscope, in which damage scores in the 24-hour and 48-hour groups were higher than in the 6-hour group and no difference was found between the two groups. Moreover, less of goblet cells or other epithelial cells adjacent to the injured surface migrated into the wound to cover the denuded area. The number of goblet cells was substantially decreased in the three CLP groups compared with the sham-operation group. Protein levels of IL-1 and TNF-α were significantly increased by 3-4 fold at all time points when compared with the sham-operation group, and cleaved caspase-3 by 4 fold. Although TFF3 expression was modestly increased for 6 hours after the onset of CLP, it appeared to decline at 24 hours and 48 hours as shown by Western blot. A similar tendency was observed upon TGF-β1, i.e. the protein level was not elevated at 24 hours and 48 hours, but increased modestly at 6 hours.CONCLUSIONS:Sepsis from CLP shows less restitution on the surface of injured intestinal mucosa. There is evidence that both constant inflammatory reaction and epithelial cell apoptosis may affect mucosal reestablishment of the intestine at the onset of sepsis. Mucosa after severe sepsis showed the state of high inflammation, and declined goblet cell function and mucosal reconstruction, which affected the repair of damaged intestinal barrier. Constant inflammatory reaction, and declined goblet cell function and mucosal reconstruction ability may affect the reestablishment of intestinal mucosa at the onset of sepsis.

Objective To investigate whether mesenchymal stem cells can promote the recovery of acute renal tubular damage induced by mercuric chloride and to explore its possible mechanism.Methods Acute renal failure rat model was established by intraperitoneal injection of mercuric chloride.SD rats were randomly divided into three groups which were MSCs injection group, saline infusion group and normal control group.Seven days later,the changes of rat weight,survival,renal function and pathology were observed;PCNA,ED-1 and GFP were detected by immunohistochemistry; The expression of cytokines in kidney and the distribution of GFP plasmid-transfected MSCs in kidney were examined by RT-PCR.Results MSCs infusion ameliorated the decline of rat weight,survival, renal function,and pathological changes.PCNA and ED-1 positive cells in MSCs group were fewer than those in saline group.Expression of growth factors EGF,PDGF,HGF were obviously up- regulated and pre-inflammatory cytokines TNF-?was significantly reduced in MSCs-treated kidneys. GFP-labelled MSCs occurred occasionally in renal interstitium of MSCs-treated rats,but not in renal tubules.Conclusions Bone marrow mesenchymal stem cells can promote the recovery of acute renal tubular epithelial cells damage caused by mercuric chloride.The mechanism may partly depend on regulating the excretion of cytokines in renal microenvironment rather than completely depend on their differentiation to tubular cells.