In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility, a series of novel pharmaceutical dosage forms as solid dispersion, liposome, microemulsion, vesicle, cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years. Among which drug nanocrystal attracts more attentions for its simpler preparation method, higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes. In this paper, the nanocrystals of the poorly-water soluble drugs prepared based on bottom-up and top-down technologies were introduced. The characteristics and applications of the nanocrystal-based dosage forms as suspension, tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics, pharmacodynamics and tissue targeted drug distribution after delivery by oral administration, intravenous injection and pulmonary inhalation. The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism. Finally, the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.

The survey of traditional knowledge related to Chinese materia medica resources is the important component and one of the innovative aspects of the fourth national survey of the Chinese materia medica resources. China has rich traditional knowledge of traditional Chinese medicine (TCM) and the comprehensive investigation of TCM traditional knowledge aims to promote conservation and sustainable use of Chinese materia medica resources. Building upon the field work of pilot investigations, this paper introduces the essential procedures and key methods for conducting the survey of traditional knowledge related to Chinese materia medica resources. The essential procedures are as follows. First is the preparation phrase. It is important to review all relevant literature and provide training to the survey teams so that they have clear understanding of the concept of traditional knowledge and master key survey methods. Second is the field investigation phrase. When conducting field investigations, survey teams should identify the traditional knowledge holders by using the 'snowball method', record the traditional knowledge after obtaining prior informed concerned from the traditional knowledge holders. Researchers should fill out the survey forms provided by the Technical Specification of the Fourth National Survey of Chinese Materia Medica Resources. Researchers should pay particular attention to the scope of traditional knowledge and the method of inheriting the knowledge, which are the key information for traditional knowledge holders and potential users to reach mutual agreed terms to achieve benefit sharing. Third is the data compilation and analysis phrase. Researchers should try to compile and edit the TCM traditional knowledge in accordance with intellectual property rights requirements so that the information collected through the national survey can serve as the basic data for the TCM traditional knowledge database. The key methods of the survey include regional division of Chinese materia medica resources, interview of key information holders and standardization of information.' In particular, using "snowball method" can effectively identify traditional knowledge holder in the targeted regions and ensuring traditional knowledge holders receiving prior informed concerned before sharing the information with researcher to make sure the rights of traditional knowledge holders are protected. Employing right survey methods is not only the key to obtain traditional knowledge related to Chinese materia medica resources, but also the pathway to fulfill the objectives of access and benefit sharing stipulated in Convention on Biological Resources. It will promote the legal protection of TCM traditional knowledge and conservation of TCM intangible, cultural heritage.
China ; Data Collection ; Databases, Pharmaceutical ; Drugs, Chinese Herbal ; Materia Medica ; Medicine, Chinese Traditional

The ergosterols were produced from corn straw hydrolysates fermented by ergosterol yeast,which was obtained from protoplast electrofusion.The effects on the yield of ergosterol were studied in the condition of shaker,such as initial sugar concentration,nitrogen source,pH value and fermentation time.The technical conditions were optimized according to the DPS center-united experimental design principles and the method of response surface analysis with four factors and three levels.The results indicated that the four factors had significant correlation to ergosterol accumulation.The biomass and the ergosterol content could be up to 8.67g/L and 2.37% respectively after cultivated for 32h under optimal technical condition.The structure of ergosterol crystal was characterized by UV,IR and SEM.A new approach of biomass source application was presented.

Objective To investigate the distribution situation of human papillomavirus (HPV) genotypes profile in cervical cells among women in Xuzhou area and its clinical significance .Methods 23 kinds of HPV DNA were extracted in cervical cell samples from 8 010 women in Xiuzhou area .The gene‐chips technique of PCR combined with reverse dot blot was adopted to detect the HPV genotypes .Results Among 8010 cervical cell samples ,there were 1 852 HPV infected cases ,the total HPV infection rate was 23 .12% ,the HPV infection rates of single type accounted for 17 .17% and its predominant types were 16 type (4 .35% ) ,followed by 58 type (2 .12% ) and 52 type (1 .82% ) ,The detection rate of multiple HPV infection was 5 .96% ,in which the predominant types were HPV16+58(4 .40% ) ,16+52(2 .94% ) ,11+16(2 .52% ) .Conclusion The single HPV infection of HPV16 ,58 ,52 and the multiple HPV infection of HPV16+58 ,16+52 ,11+16 are the main genotypes of cervical cells among women in Xuzhou area , this gene chip technique is suitable for the cervical cell sample ,its once detection can detect 23 kinds of HPV genotypes with high specificity and high sensitivity ,which has an important significance for the molecular epidemiologic survey study of HPV genotypes distribution among women in our country .

OBJECTIVETo explore the effects of safflower injection on prevention and treatment of hypoxic pulmonary hypertension and clarify the function of the endoplasmic reticulum stress apoptosis pathway during the process.

METHODSThirty male SD rats were randomly grouped as normal control group, hypoxia-hypercapnia group and hypoxia+safflower group. The latter two groups were put in the cabin with oxygen concentration ranged from 9% to 11% and carbon dioxide concentration from 5% to 6%. The pulmonary artery pressure and the index of right ventricular hypertrophy were determined after hypoxia exposure (8 h/dx28 d). Changes in morphology of lung tissue were observed by electron microscopy. To explore the possible mechanisms, we also detected apoptosis and apoptosis-related genes/proteins in lung tissue by TUNEL reactivity and PCR and Western blot.

RESULTSCompared with the normal control group, pulmonary artery pressure and the index of right ventricular hypertrophy in hypoxia group were 45% and 33.4% higher, respectively. Tiny blood vessel wall of lungs was thickened and edema, and proliferation of collagen fibers was obvious under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed more high brightness green fluorescence (+-++), but less green fluorescence showed in the pulmonary vascular smooth muscle cell layer, and apoptosis index (AI) value was 150% higher; gene and protein expression levels of endoplasmic reticulum stress pathway were increased. Compared with hypoxia-hypercapnia group, pulmonary artery pressure and the index of right ventricular hypertrophy in the hypoxia+safflower group were 18% and 15.6% lower, respectively; collagen fibers were decreased, and smooth muscle cells and epithelial cells were got apoptotic-like changes under the electron microscope. TUNEL staining of apoptotic cells in lung tissues showed brighter green fluorescence (++-+++); the high brightness green fluorescence showed in pulmonary vascular smooth muscle cell layer, and apoptotic index (Al) value was 40% higher; gene and protein expressions of endoplasmic reticulum stress pathway were significantly upregulated.

CONCLUSIONOur findings demonstrate that safflower injection could activate endoplasmic reticulum stress-induced apoptosis and especially promote apoptosis in pulmonary vascular smooth muscle cells.

Animals ; Apoptosis ; drug effects ; Carthamus tinctorius ; chemistry ; Endoplasmic Reticulum Stress ; drug effects ; Hypercapnia ; physiopathology ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Hypoxia ; physiopathology ; Lung ; cytology ; physiopathology ; Male ; Myocytes, Smooth Muscle ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the role of autophagy inhibitor chloroquine (CQ) in the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in hypoxia conditions.

METHODSThe following groups in this study were set up: control group, hypoxia group, 50 micromol/L CQ + hypoxia group, 50 micromol/L CQ group. The viability of PASMCs in every group was detected by MTT assay. Autophagic vacuoles in the cells were observed by MDC staining. Protein expression of microtubule associated protein light chain 3 (LC3) was measured by Western blot. Migration of PASMCs was detected by wound healing assay.

RESULTSCompared with control group, no effect on the viability of PASMCs was observed treated by CQ alone. In 1% hypoxia group, cell viability increased significantly compared with that in control group. The number of autophagic vacuoles and the rate of cell migration and also protein expression of LC3-II were also markedly increased. Compared with hypoxia group, addition of CQ increased the number of autophagic vacuoles and the levels of LC3-II protein, but decreased the proliferation and migration of PASMCs.

CONCLUSIONHypoxia could activates autophagy and contributes to proliferation and migration of PASMCs, and autophagy inhibitor CQ could decrease the effect of hypoxia on PASMCs through inhibiting autophagy process.

Autophagy ; drug effects ; Cell Hypoxia ; Cell Movement ; Cell Survival ; Cells, Cultured ; Chloroquine ; pharmacology ; Humans ; Microtubule-Associated Proteins ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; Pulmonary Artery ; cytology

Objective To analyze the data of road traffic accidents, deaths and injuries in 31 provinces and municipalities in China from 2010 to 2017, and to predict that the number of deaths and injuries caused by road accidents set in the sustainable development goals (SDGs) will be halved by 2020 compared with the target set in 2015. Methods Describing and analyzing the current situation of road traffic accidents in 31 provinces and municipalities in China, and using the trend extrapolation method to predict whether the SDGs target can be achieved by 2020. Results The numbers of traffic accidents, deaths and injuries in Guangdong, Jiangsu, Zhejiang and Shandong Provinces showed a downward trend from 2010 to 2017, but still ranked the front in China. In 2017, Beijing had the highest death rate followed by Guizhou as the second, and Guizhou had the highest injury rate followed by Tianjin as the second. The projected results showed that the numbers of deaths and injuries caused by road traffic accidents in China would be increased by 17% and 1.3% respectively in 2020 indicating that SDGs target could not be met. Among the 31 provinces/municipalities, it was predicted that the numbers of deaths and injuries in Hunan would be reduced to 50.7% and 65.3% in 2015, respectively by 2020, and the target could be achieved; the number of injuries in Shanghai was decreased by 83.3%, but the deaths was only decreased by 34.5%, and there was still a gap with the target; the rest 29 provinces/municipalities could not meet SDGs target. It was expected that the deaths in 11 provinces and municipalities would increase by 2020, with Beijing, Jilin, Jiangxi, Hubei and Guizhou Provinces showing the most significant growth. The number of injured people in 8 provinces and municipalities shows an increasing trend, with Jilin, Jiangxi, Hubei and Guizhou provinces showing significant growth. Conclusions Except for Hunan Province, it was difficult for the whole country and the rest provinces and municipalities to reach the SDGs target. According to the forecast results and the actual situation, a targeted scientific prevention and control strategy can be formulated. The measures taken by Hunan and Shanghai in traffic accident prevention and control were effective and worth learning.

OBJECTIVETo study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD).

METHODSTwenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected.

RESULTSThere were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene.

CONCLUSIONSASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.

Adult ; Aged ; CD3 Complex ; metabolism ; Epstein-Barr Virus Infections ; pathology ; Female ; Follow-Up Studies ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Granzymes ; metabolism ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Killer Cells, Natural ; pathology ; Lymphoproliferative Disorders ; drug therapy ; genetics ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Poly(A)-Binding Proteins ; metabolism ; RNA, Viral ; metabolism ; Retrospective Studies ; Survival Rate ; T-Cell Intracellular Antigen-1 ; T-Lymphocytes ; pathology ; Young Adult

Cell Line ; DNA, Viral ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Humans ; Ribonucleases ; genetics ; Transfection ; Virus Replication

OBJECTIVETo investigate the relationship between caspase 12 activation and endoplasmic reticulum stress mediated apoptosis of guinea pig cochlea cells induced by intense noise.

METHODSThirty-two guinea pigs were randomly divided into 4 groups. The guinea pigs in the experiment groups were exposed to 4 kHz narrow band noise at 120 dB SPL for 4 h. After the noise expose for 1, 4, 14 days of the experiment guinea pigs, auditory brainstem response (ABR) of the guinea pigs on experiment and control groups were tested before decapitated. Four guinea pig's cochleae of every group were taken to paraffin section, and the rest was extracted the total protein. Apoptosis was tested by terminal deoxynucleotidyl transferase (TDT)-mediated deoxyuridine triphosphate (d-UTP) nick and labeling method (TUNEL) and transmission electron microscopy. Expression of caspase 12, Bip/GRP78 was tested by immunohistochemistry and Western blot methods.

RESULTSThe observation by transmission electron microscopy showed the features characteristic of apoptotic cells in the Corti and SGC of 1d after the noise expose, but no in the control. There were higher expressions of Tunel-Positive cells in the OHC, SGC and SV of experiment groups, and there was significant differences compared with the control group (P < 0.01). Protein levels of Bip/GRP78 and caspase 12 were risen up after noise exposed, and there all were significant differences compared with the control group (P < 0.01).

CONCLUSIONIntense noise causes cochlea cell lesion by inducing apoptosis to result in and caspase 12 induced endoplasmic reticulum stress-related apoptosis plays an important role in the procedure of apoptosis.

Animals ; Apoptosis ; Caspase 12 ; metabolism ; Cochlea ; cytology ; metabolism ; pathology ; Endoplasmic Reticulum ; metabolism ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Hair Cells, Auditory, Outer ; metabolism ; pathology ; Male ; Noise ; adverse effects