OBJECTIVETo observe the clinical effect of tadalafil combined with testosterone undecanoate on late-onset hypogonadism (LOH) in old and middle-aged males.

METHODSA total of 125 old and middle-aged (40 to 60 years) males with LOH were randomly assigned to a treatment group (n = 65) and a control group (n = 60) to be treated with tadalafil + testosterone undecanoate and testosterone undecanoate alone, respectively. We compared the levels of total testosterone (T), IIEF scores and the patients' sexual encounter profile (SEP) diaries before and 4 weeks after medication.

RESULTSThe T level, IIEF score and SEP score were significantly improved in both groups after medication as compared with the baseline (P < 0.05), and even more so in the treatment than in the control group (P < 0.05).

CONCLUSIONTadalafil combined with testosterone undecanoate, superior to testosterone undecanoate alone, can improve the T level, IIEF score and SEP score in old and middle-aged males with LOH and increase their sexual satisfaction and self-confidence.

Carbolines ; therapeutic use ; Erectile Dysfunction ; etiology ; Humans ; Hypogonadism ; drug therapy ; physiopathology ; psychology ; Male ; Middle Aged ; Sexual Behavior ; Tadalafil ; Testosterone ; analogs & derivatives ; analysis ; therapeutic use ; Treatment Outcome

OBJECTIVETo establish the 3T3 mouse fibroblast neutral red uptake (NRU-PT) phototoxicity test method, and evaluate the practicality of the method in detecting potential phototoxicity of the cosmetic products.

METHODSFifteen phototoxic and 9 non-phototoxic chemicals were tested in our laboratories, the phototoxic potential of the test chemicals was evaluated in a prediction model in which either the photo irritation factor (PIF) or the mean photo effect (MPE) was compared with the coherence and sensitivity of the method. 20 kinds of functional cosmetics were detected and the results were analyzed by the 3T3 NRU-PT in vitro and Guinea pig skin phototoxicity test (in vivo).

RESULTSBoth PIF and MPE of the chemicals were highly reproduced, and the correlation between in vitro and in vivo data was almost perfect. All the non-phototoxic provided a negative result, while 14 of the 15 phototoxic tested chemicals gave clear positive results. For cosmetics, the correlation between in vitro and in vivo data was consistent.

CONCLUSIONThe 3T3 NRU PT test was established successfully, it should be used as a good alternative method for assessing the phototoxic potential of the chemicals and cosmetics in China.

3T3 Cells ; drug effects ; Animals ; Animals, Newborn ; Cosmetics ; toxicity ; Dermatitis, Phototoxic ; Fibroblasts ; drug effects ; Guinea Pigs ; Mice ; Toxicity Tests

OBJECTIVEThis study aims to establish and evaluate the methodology of isolated rabbit eye (IRE) test.

METHODSIRE test was performed according to modifications of the in vitro toxicology (INVITTOX) Protocol No.85: Rabbit enucleated eye test by European Centre for the Validation of Alternative Methods (ECVAM), and then 26 chemicals and 26 cosmetic products were tested in both in vitro IRE and in vivo Draize tests. A statistical analysis was conducted to determine the relevance of the IRE test to the data generated in the Draize test.

RESULTSIRE test was established successfully in our laboratory. It was shown that ranking correlation and class concordance were fairly well between the IRE test and the Draize test for 26 reference chemicals (Fisher's Exact Test χ(2)=51.314, P<0.001; McNemar P=0.261; Gamma=0.960, P<0.001; Kappa=0.843, P<0.001) and 26 cosmetic products (Fisher's Exact Test χ(2)=15.522, P<0.001; McNemar P=0.311; Gamma=0.967, P<0.001; Kappa=0.611, P<0.001).

CONCLUSIONIRE test was established successfully for in vitro testing of eye irritation as an alternative to Draize test.

Animal Testing Alternatives ; Animals ; Cosmetics ; toxicity ; Eye ; drug effects ; Irritants ; toxicity ; Rabbits ; Toxicity Tests ; methods

BACKGROUNDWith the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.

METHODSAll infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.

RESULTSA total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.

CONCLUSIONSOur study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

China ; Female ; Humans ; Infant ; Infant Mortality ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Morbidity ; Respiratory Distress Syndrome, Newborn ; mortality ; Retrospective Studies ; Surveys and Questionnaires

Xiaojin Pill, was firstly recorded in Life-saving Manual of Diagnosis and Treatment of External Diseases, with its primitive name of "Xiaojin Dan". Xiaojin Pill is a classic prescription for treating carbuncle and it is the first choice for Chinese medicine in the clinical treatment of hyperplasia of mammary glands. In this paper, the literature reports on Xiaojin Pills were summarized and the historical evolution, material basis, pharmacological action, quality control and other problems were systematically discussed to explore the potential problems in every aspect of the development status, and put forward the development countermeasures, providing reference for the modernization research and development of Xiaojin Pills.
Capsules ; Drugs, Chinese Herbal ; Quality Control ; Research

According to folk usage of Aconitum carmichaelii Debx., the present study was designed to determine the feasibility of the stems and leaves of Aconitum carmichaelii Debx. as a new medicinal resource. Fourteen alkaloids in mother roots, fibrous roots, stems, and leaves of Aconitum carmichaelii Debx. were measured by HPLC-MS/MS. And multivariate analysis methods, such as clustering analysis and principal component analysis, were applied to analyze the difference among various parts. In addition, the acute toxicity, analgesia, and anti-inflammatory tests were carried out. The results suggested that the contents of alkaloids in mother roots and fibrous roots were approximate, but those of leaves and stems were different from mother roots and fibrous roots. The results of the acute toxicity testing demonstrated the toxicity of fibrous root was strongest, and mother roots were slightly less toxic than fibrous roots. The stems and leaves were far less toxic than mother and fibrous roots. In addition, the analgesia and inflammatory tests showed the effects of the various tissues had no difference each other. These results provided a basis for developing new complementary and alternative treatments for rheumatoid arthritis patients. Simultaneously, the approach may also turn wastes into treasure and promote the development of circular economy.
Aconitum ; chemistry ; Alkaloids ; administration & dosage ; chemistry ; toxicity ; Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; toxicity ; Arthritis, Rheumatoid ; drug therapy ; Chromatography, High Pressure Liquid ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Female ; Humans ; Male ; Mice ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Tandem Mass Spectrometry

Current evaluation method for astringency is mainly focused on human sensory evaluation. However, it is subjective, vague, and short of assessment indicators for objective quantification. In this paper, the quantification method for astringent intensity of traditional Chinese medicine was established based on the animal preference index and electronic tongue in vitro and in vivo. Firstly, the standard substance of astringency, tannic acid, was used for the methodology optimization and validation of two-bottle preference test. It was determined that the standard experimental animals were female rats of 140-180 g. The functional relationship between concentration of tannic acid and preference index was obtained Y= ln(1.682 6－0.441 66X), r=0.997 3. Then the typical astringent Chinese herbs Chebulae Fructus, Ardisiae Japonicae Herba, Canarii Fructus, Catechu, and Arecae Pericarpium were evaluated by the optimized method. Their corresponding concentration of tannic acid was converted by the concentration-preference index relationship through preference index. Their astringency was equivalent to 0.56, 0.29, 0.24, 0.34, 0.25 g•L⁻¹ tannic acid. Finally, the results were verified by electronic tongue. The correction analysis between Euclidean distance in PCA and preference index and concentration of tannic acid converted by samples showed a high correlation through pearson correlation analysis. The above results indicated that the method was objective, true and reliable. The method provided a reliable tool for the quantification of astringency and evaluation of taste masking effect for Chinese medicines, and also offered a new idea and model for the quantification of taste in the pharmaceutical and food fields.

OBJECTIVETo evaluate the efficacy and safety of Chinese medicine (CM) plus Western medicine (WM) in the treatment of pediatric patients with severe hand, foot and mouth disease (HFMD) by conducting a prospective, controlled, and randomized trial.

METHODSA total of 451 pediatric patients with severe HFMD were randomly assigned to receive WM therapy alone (224 cases, WM therapy group) or CM [Reduning Injection ( ) or Xiyanping Injection ()] plus WM therapy (227 cases, CM plus WM therapy group) for 7-10 days, according to a web-based randomization system. The primary outcome was fever clearance time, which was presented as temperature decreased half-life time. The secondary outcomes included the rate of rash/herpes disappearance within 120 h, as well as the rate for cough, runny nose, lethargy and weakness, agitation or irritability, and vomiting clearance within 120 h. The drug-related adverse events were also recorded.

RESULTSThe temperature decreased half-life time was 40.4 h in the WM therapy group, significantly longer than 27.2 h in the CM plus WM therapy group (P<0.01). Moreover, the rate for rash/herpes disappearance within 120 h was 43.6% (99/227) in the CM plus WM therapy group, significantly higher than 29.5% (66/224) in the WM therapy group (P<0.01). In addition, the rate for cough, lethargy and weakness, agitation or irritability disappearance within 120 h was 32.6% (74/227) in the CM plus WM therapy group, significantly higher than 19.2% (43/224) in the WM therapy group (P<0.01). No drug-related adverse events were observed during the course of the study.

CONCLUSIONThe combined CM and WM therapy achieved a better therapeutic efficacy in treating severe HFMD than the WM therapy alone. Reduning or Xiyanping Injections may become an important complementary therapy to WM for relieving the symptoms of severe HFMD. (Registration No. NCT01145664).

Based on the principle of particle design, the powder of Xiaojin Pills was prepared, and the quality uniformity was investigated by means of powder characterizations and content uniformity. By studying the mixed crushing rules of the classified materials and the design principle of the powder particles of Chinese medicine, the powder of the Xiaojin Pills was prepared. At the same time, the manmade mixed powder and the control powder prepared by pharmacopoeia were prepared. The mixed homogeneity of the three powders was evaluated by particle size distribution and color difference. The GC-MS and LC-MS/MS were used to study the homogeneity of their contents. The best preparation process of particle design powder is:materials easily crushed are smashed for 50 min in the vibrating ultrafine mill with -15℃, then add the materials difficultly crushed into the mill and let them crushed together for 3 min. The particle size range of manmade mixed powder was the largest with the particle size difference being more than 100 microns, the RSD value being 26.07%. The particle size range was more than 50 microns in the powder prepared by pharmacopoeia, and the RSD was nearly 15%. The difference in particle size was only around 4 μm and the RSD value was 3.18%. The color difference test showed that the composite chromatism (dE^*) value of the powder prepared by pharmacopoeia was the largest for the RSD was 84.56%. The RSD of manmade mixed powder and the powder prepared by Pharmacopeia were 53.83% and 32.83%, respectively. The RSD value of the particle designed powder's muscone content is about 50% of the other two kinds of powders. The contents of 10 components in powders were determined by LC-MS/MS. The RSD values of the particle designed powder were much smaller than other two kinds of powders. Results indicate that the uniformity of the particle designed powder is better than other two kinds of powders. Chinese medicine particle design technology can effectively improve the uniformity of traditional Chinese medicine powder.

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.