OBJECTIVETo investigate the effect and mechanism of arsenic trioxide on hepatoma cell line BEL-7402 and observe the effect and best administration method of arsenic trioxide on hepatocellular carcinoma patients who were not suitable for operation.

METHODSThe cell activity and morphologic changes were studied after being treated with arsenic trioxide in different concentrations. The apoptosis was detected by flow cytometry assay and DNA fragmentation assay. The caspase-3 level of mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and fluoro-spectrophotometer. The growth inhibition of implant tumor was observed in nude mice treated with arsenic trioxide in different concentrations. Arsenic trioxide was used in hepatocellular carcinoma patients by intravenous dropping and continuous regional infusion through hepatic artery.

RESULTSThe effect of arsenic trioxide on hepatoma cell lines was dependent on the time and concentration obviously. The decrease in cell number was preceded by morphological changes in the treated BEL-7402 cells that were characteristic of apoptosis, including membrane blebbing, shrunken cytoplasm, nuclear condensation and loss of adhesion. Flow cytometry assay showed an arrestment at G(2)/M phase and sub-G(1) cell peak. DNA fragmentation assay showed a marked DNA ladder. The mRNA level of caspase-3 was no change in RT-PCR whereas the protein of caspase-3 was increased after added As(2)O(3) 1 - 36 h. Caspase-3 activity began to increase after 2 h and reached a maximal level after 12 h in a linear fashion. Then, the level of caspase-3 was decreased, but still in a high level. The growth inhibition of implant tumors was obviously in nude mice. The intravenous usage of arsenic trioxide could improve the quality of life with low toxicity in hepatocellular carcinoma patients not suitable for operation. The tumor size decreased in 30 patients and AFP value decreased in 19 patients by continuous regional infusion through hepatic artery.

CONCLUSIONSArsenic trioxide can obviously inhibit the growth of hepatoma cell line BEL-7402 through inducing hepatoma cell apoptosis. The activation and increase of Caspase-3 is the possible mechanism of apoptosis, and the acting point is in pro-enzyme level. The best result of arsenic trioxide on non-operative patients should be gotten in continuous infusion through hepatic artery.

Adult ; Aged ; Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Line, Tumor ; Chemotherapy, Cancer, Regional Perfusion ; Female ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Liver Neoplasms, Experimental ; pathology ; Male ; Mice ; Mice, Nude ; Middle Aged ; Oxides ; pharmacology ; therapeutic use

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

OBJECTIVETo describe the epidemiology of neural tube defects (NTDs) in high- and low-prevalence areas of China.

METHODSBirth defects surveillance data, collected from 1992 through 1994 was analyzed. These data were collected as part of the Sino-American cooperative project on NTDs prevention. We classified NTDs as anencephaly, encephalocele, high-level and low-level spina bifida (SB) according to location of the lesion (high vs low) and whether the defect was isolated or occurred in association with other birth defects. Rates were compared in the high-prevalence (North) region and the low-prevalence (South) region, after adjusted for classification, urban and rural, season and sex, and calculated the adjusted rate of NTDs.

RESULTSAmong seven hundred and eighty-four NTDs cases in 326 874 recorded births (include in livebirth, stillbirth and fetal death with a gestational age of at least 20 weeks), the overall NTDs prevalence in the North was 5.57/1,000 births, and in the South was 0.88/1 000. There were also significant differences in the prevalence of anencephaly, encephalocele, high-level and low-level SB between North (0.97, 0.49, 2.75 and 1.11/1,000 birth) and South (0.36, 0.15, 0.21 and 0.14/1,000 birth) (P < 0.01), with adjusted prevalences in the North 3 - 7 times higher than those in the South. There were significant difference between urban (2.04) and rural areas (6.57/1,000 birth) in the North (P < 0.01), urban (0.52) and rural areas (0.95/1,000 birth) in the South (P < 0.05). Adjusted prevalence rates in the rural were 3 - 4 times higher than those of urban in the North and 1.6 - 1.9 times higher than in the South; The seasonal rate of high-level SB increased between September and November in the North (3.44/1,000 birth), while the seasonal rate of anencephaly decreased between September and November (0.18/1,000 birth) in the South. However there were no seasonal changes in other classified NTDs both in the South and North.

CONCLUSIONSThe birth prevalence of NTDs in the North of China was the highest in the world. There were significant differences between the North and the South, urban and rural. There was seasonal change in high-level SB in the North, which was in accordance to the phenotype of NTDs. It was suggested that there might exist etiological heterogeneity among anecephalus, low- and high-level SB.

China ; epidemiology ; Female ; Humans ; Incidence ; Male ; Neural Tube Defects ; epidemiology ; Seasons

China has a long history of the international trade of traditional Chinese medicine(TCM).And the export products mainly composed of Chinese herbal medicine and its extracts with Chinese patent herbal medicine and health care products as complementary items.The international trade of TCM faces problems of structural disequilibrium in export products and trade barriers.In this study,we used Michael Porter's diamond model to analyze the international competitiveness of TCM industry.We found that TCM industry in China was rich in production factors and broad in market demands,but lack of the related and supporting industries.In addition,compared with the herbal medicine manufacturers in European,American and Japanese,enterprises in China were weaker in the strategy making,market positioning and industry competing.The development of the international market of herbal medicine,the arrival of the aging society,and the introduced policies of the TCM,provide great opportunities for TCM industry' s development.In order to improve the competitiveness of the TCM industry,we propose to increase the international recognition of TCM by developing clinical study,cope with international trade barrier by strengthen international standardization research,and improve the competitiveness of TCM industry by economies of scale formed by the accumulation of the pharmaceutical industry.
China ; Drugs, Chinese Herbal ; economics ; Medicine, Chinese Traditional ; economics ; Models, Economic

It is crucial to establish a complete set of traditional Chinese medicine(TCM) quality traceability management process system, in order to stabilize the pricing order of TCM market and reconstruct the transmission path of TCM quality signals. In this study, we reviewed the mature experience of food and drug supervision at home and abroad, analyzed the quality characteristics of TCM, and put forward that the quality control of TCM products can learn from the hazard analysis and critical control point(HACCP) system in food safety quality control. This study points out that the HACCP system provides not only technical guidance for the traceability management of TCM, but also ideas for improving the quality of TCM products and the safety risk control of TCM. The application of the HACCP system in TCM quality control can help establish an international dialogue platform for TCM and help realize the modernization and internationalization of TCM industry.
Biological Products ; Drugs, Chinese Herbal ; Hazard Analysis and Critical Control Points ; Medicine, Chinese Traditional ; Quality Control

Poria cocos is one of medical materials frequently used in China and well marketed at home and abroad. Based on the analysis of exports and imports data of P. cocos, we found that large proportions of P. cocos were exported, while only a small proportions of those were imported in China between 2011 and 2016. During periods of these six years, the annual exporting trade of P. cocos in quantity significantly decreased, but that in dollars tend to increase slightly and the unit-prices of P. cocos significantly increased. Statistically, the average annual export trade of P. cocos from 2011 to 2016 in quantity and dollars were 9 279.73 tons and 35.454 million dollars, respectively. And the average annual export in unit-price was 4.14 dollars per kilogram. In total, P. cocos came from 29 provinces and exported to 44 countries through 21 ports. More than 98% of total exports of P. cocos were flew to the markets of countries in Asia, of which Hong Kong was the major partner in import trade of P. cocos. Large amount of P. cocos came from Guangdong province and exported mainly through Shenzhen port. Except the exports, China also imports P. cocos from other countries, among which Korea was the major country exports largest amount of P. cocos to China. And most of P. cocos were imported by Jilin province and mainly through Changchun port. To improve the export kinetic, quality and profits of P. cocos, and thus enhance the international competitiveness of the industry of P. cocos, Chinese governments should emphasize the researches on the products of P. cocos, broaden the demand space of the high-end customers, stimulate the high-end market grow in high speed and accelerate the process of standardization in future.
China ; Commerce ; Republic of Korea ; Wolfiporia

Dao-di herbs have been synonymous with quality medicinal herbs in our mind hearts since ancient times and are the essence of Chinese medicine culture. The development of genuine regional herbs faces problems such as insufficient supply of local resources and lack of competitive advantages. It is necessary to seek a suitable model to protect and develop authentic medicinal materials. The protection mode of geographical indication products has become more mature. Geographical indication(GI) products and authentic medicinal materials are all related to the origin. There is certain commonality between them. However, there are also differences between authentic Chinese herbal medicines and geographical indications, and it is unsuitable to simply equate the authentic Chinese medicinal materials with GI products. This article comprehensively combs and compares the development of the authentic Chinese herbal medicines and geographical indication products, and believes that it is necessary to fully learn from the experience of GI products and combine the characteristics of authentic medicinal materials to establish a set of protection systems that meet the characteristics of authentic medicinal materials. Through this research, it has positive significance to promote the protection and management of authentic medicinal materials.
Drugs, Chinese Herbal ; Geography ; Medicine, Chinese Traditional ; Plants, Medicinal ; growth & development ; Research

The three objectives of the Convention on Biological Diversity (CBD) are the conservation of biological diversity, the sustainable use of its components and the fair and equitable sharing of benefit sarising from the utilization of genetic resources.The Nagoya Protocol significantly advances the CBD's third objective by providing a strong basis for greater legal certainty and transparency for both providers and users of genetic resources.In June 2016, the Chinese government approved the accession to the Nagoya Protocol. The implementation of the Nagoya Protocol is bound to greatly influence the traditional Chinese medicine (TCM) as its development relies on medical biological genetic resources.Both the protection and access of medical biological genetic resources and its related traditional knowledge and the introduction, breeding, biosynthesis and the extraction and modification of effective components of medicinal organism are with the prescribed scope of the Nagoya Protocol. In this study, we simply introduce the background and main contents of the Nagoya Protocol in first. We then explore the relationship between the Nagoya Protocol and the TCM.We also analyze the positive effects on the TCM for China to be one of the parties of the Nagoya Protocol and finally make some proposals for better implementation of the Nagoya Protocol.This study has certain reference significance to the resource economy and management of TCM.
Biodiversity ; China ; Conservation of Natural Resources ; Medicine, Chinese Traditional ; standards

The study aims to investigate spatial distribution pattern and age structure of wild Angelica sinensis in Gansu province.Ten plots each with an area of 100 m2 were set and the spatial coordinates of all wild A. sinensis individuals were measured within each plot. Based on plant individual mapping data,we explored the spatial distribution pattern and its differences between different life history stages of wild A. sinensis in Gansu province by using nearest neighbor distance statistics. Correlation analysis were carried out to explore the relationship between spatial aggregation degree and topographic factors. We also distinguished individuals to three life history stages( i.e. seedlings,adults and boltings) and then test the differences among/between them using nonparametric test.(1)We found that the dominant spatial distribution pattern of wild A. sinensis population in Gansu was aggregated distribution. There was no significant correlation between spatial aggregation degree of wild A. sinensis and altitude,slope and aspect. There was no significant difference between the average distance from seedlings to their nearest bolting individuals; the average distance from adult individuals to their nearest seedlings was significantly larger than the average distance from adult individuals to their nearest adult individuals; and the average distance from bolting individuals to their nearest adult individuals was significantly smaller than the average distance from bolting individuals to their nearest bolting individuals.(2)The age structure was showed as a declining population,characterized by less seedlings and bolting individuals,while more adult individuals within population. The population characteristics of wild A. sinensis,characterized by aggregated distribution pattern and senescent type of age structure,are disadvantage to its population development. The factors,such as habitat specialization,human activities and intraspecific competition,which shapes the current population characteristics,may increase the threatened status of wild A. sinensis. We suggest to strengthen the protection of wild A. sinensis.
Altitude ; Angelica sinensis ; growth & development ; China ; Conservation of Natural Resources ; Ecosystem ; Seedlings ; Spatial Analysis

Ex-situ conservation is an important means to protect biological genetic resources. Resource protection has received more and more attention with the continuous improvement of the comprehensive utilization of traditional Chinese medicine resources. In this paper, the research and compilation of the species list of ex-situ cultivated medicinal plants in 12 Chinese Academy of Sciences botanic gardens and 19 specialized medicinal botanic gardens in China were carried out. Based on the Species 2000(2017) and other classification databases, species diversity of medicinal plants ex-situ cultivated in these botanical gardens were analyzed. The study found that there were 16 351 higher plant species in our country, belonging to 276 families and 1 936 genera. Of these, 6 949 specieswere medicinal plants, accounting for 50.4% of the total medicinal plants. There were 1 280 medicinal plants were in threatened status, accounting for 19.6% of all threatened species in the Chinese Biodiversity Red List, with ex-situ cultivated proportion of 59.5%. And 3 988 medicinal plants were Chinese endemic species, accounting for 22.5% of all Chinese endemic species, with ex-situ cultivated proportion of 53.3%. This article has reference significance for the management and protection of medicinal plant resources.