Cryopreservation Conditions of Carthamus tinctorius Seeds / 中国实验方剂学杂志

ObjectiveTo study on the suitable cryopreservation conditions of Carthamus tinctorius seeds. MethodThe germination rate，relative conductivity，soluble sugar，soluble protein， and related enzyme activities of C. tinctorius seeds， as well as the hydroxysafflor yellow A （HSYA） content in Carthami Flos after storage and breeding for four months were detected under different temperature conditions （long-term storage，medium-term storage，short-term storage，room temperature，and ultra-low temperature refrigerator），different water content （8.1%，6.6%，5.2%，and 3.9%），and different storage time （2，4，6，8， 10 months）. SPSS 20.0 was used for statistical analysis. ResultDuring the storage for 10 months，the changing trend of the germination rate of C. tinctorius seeds revealed that it was more suitable to store seeds with low water content at a lower temperature. The differences in germination rate of seeds caused by storage temperature，seeds water content， and storage time were statistically significant. After storage for 10 months，the germination rate was significantly correlated with other detection indexes. ConclusionThe proper water content of C. tinctorius seeds in long-term and medium-term storage is 5.2% or 6.6%，and that in short-term and ultra-low temperature refrigerator is 3.9% or 5.2%. As revealed by the comparison results， the optimal storage conditions for C. tinctorius seeds were long-term storage and water content of 5.2%， which resulted in the highest germination rate and content of soluble sugar and soluble protein and the lowest relative conductivity after storage for 10 months. Additionally， the content of hydroxy safflor yellow A （HSYA） in Carthami Flos obtained after breeding and regeneration for four months was higher than that obtained after room temperature storage.

Composition changes reveal relationship between color and enzymatic reaction of Magnoliae Officinalis Cortex during "sweating" process / 中国中药杂志

In this study, we employed Q Exactive to determine the main differential metabolites of Magnoliae Officinalis Cortex du-ring the "sweating" process. Further, we quantified the color parameters and determined the activities of polyphenol oxidase(PPO), peroxidase(POD), and tyrosinase of Magnoliae Officinalis Cortex during the "sweating" process. Gray correlation analysis was performed for the color, chemical composition, and enzyme activity to reveal the effect of enzymatic reaction on the color of Magnoliae Officinalis Cortex during the "sweating" process. Magnoliae Officinalis Cortex sweating in different manners showed similar metabolite changes. The primary metabolites that changed significantly included amino acids, nucleotides, and sugars, and the secondary metabolites with significant changes were phenols and phenylpropanoids. Despite the different sweating methods, eleven compounds were commonly up-regulated, including L-glutamic acid, acetylarginine, hypoxanthine, and xanthine; six compounds were commonly down-re-gulated, including L-arginine, L-aspartic acid, and phenylalanine. The brightness value(L~*), red-green value(a~*), and yellow-blue value(b~*) of Magnoliae Officinalis Cortex kept decreasing during the "sweating" process. The changes in the activities of PPO and POD during sweating were consistent with those in the color parameter values. The gray correlation analysis demonstrated that the main differential metabolites such as amino acids and phenols were closely related to the color parameters L~*, a~* and b~*; POD was correlated with amino acids and phenols; PPO had strong correlation with phenols. The results indicated that the color change of Magnoliae Officinalis Cortex during "sweating" was closely related to the reactions of enzymes dominated by PPO and POD. The study analyzed the correlations among the main differential metabolites, color parameters, and enzyme activities of Magnoliae Officinalis Cortex in the "sweating" process. It reveals the common law of material changes and ascertains the relationship between color changes and enzymatic reactions of Magnoliae Officinalis Cortex during "sweating". Therefore, this study provides a reference for studying the "sweating" mechanism of Magnoliae Officinalis Cortex and is of great significance to guarantee the quality of Magnoliae Officinalis Cortex.

Variation analysis of genes associated with Usher syndrome type 1 in 136 Chinese deafness families / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the variation of genes associated with Usher syndrome type 1(USH1)in 136 Chinese deafness families from Henan province. Methods: The data of 136 deafness families tested by next-generation sequencing(NGS) which identified in the center of genetics and prenatal diagnosis of the First Affiliated Hospital of Zhengzhou University from November 2016 to December 2019 were analysized and the variation frequency of six genes related to Usher syndrome type 1(MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2) were summarized. Results: Five deafness families were detected nine pathogenic or likely pathogenic variations in two genes, accounting for 3.7% of all families. Among them, four families were caused by MYO7A variations and one family was caused by CDH23 variation. Meanwhile, seven variations of two genes were reported for the first time. They were c.313delG, c.5257dupA, c.5435A>T, c.5636G>C, c.5722T>G of MYO7A, and c.155_166del, c.4802delA of CDH23. The patients' vision of family 2 and family 3 had no obvious abnormality at present, but according to genetic diagnosis and walking dealy, they were considered to be USH1. Conclusions: MYO7A is the most common caustive gene associated with USH1 in Henan deafness patients, the application of next-generation sequencing technology can make USH1 patients diagnosed earlier before the visual symptoms appear.

Development and validation of a deep learning model to screen hypokalemia from electrocardiogram in emergency patients / 中华医学杂志(英文版)

BACKGROUND@#A deep learning model (DLM) that enables non-invasive hypokalemia screening from an electrocardiogram (ECG) may improve the detection of this life-threatening condition. This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients.@*METHODS@#We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University, Jiangxi, China, from September 2017 to October 2020. The DLM was trained using 12 ECG leads (lead I, II, III, aVR, aVL, aVF, and V1-6) to detect patients with serum potassium concentrations <3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University. The blood draw was completed within 10 min before and after the ECG examination, and there was no new or ongoing infusion during this period.@*RESULTS@#We used 6904 ECGs and 1726 ECGs as development and internal validation data sets, respectively. In addition, 1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets. Using 12 ECG leads (leads I, II, III, aVR, aVL, aVF, and V1-6), the area under the receiver operating characteristic curve (AUC) of the DLM was 0.80 (95% confidence interval [CI]: 0.77-0.82) for the internal validation data set. Using an optimal operating point yielded a sensitivity of 71.4% and a specificity of 77.1%. Using the same 12 ECG leads, the external validation data set resulted in an AUC for the DLM of 0.77 (95% CI: 0.75-0.79). Using an optimal operating point yielded a sensitivity of 70.0% and a specificity of 69.1%.@*CONCLUSIONS@#In this study, using 12 ECG leads, a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80. Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.

Analysis of Equivalence Between Traditional and Nontraditional Medicinal Varieties of Citri Reticulatae Semen from Sichuan Province / 中国实验方剂学杂志

Objective:To study the differences in genetic relationship， shape， size， and flavonoid content between traditional and nontraditional medicinal varieties of Citri Reticulatae Semen produced in Sichuan province as well as their equivalence. Method:Six batches of traditional medicinal Citri Reticulatae Semen （<italic>Citrus reticulata</italic> 'Dahongpao'） and 23 batches of nontraditional medicinal varieties were collected， and their genetic relationship was explored using sequence-related amplified polymorphism （SRAP） markers. Following the observation of their shapes and sizes under a stereomicroscope， the contents of naringin， hesperidin， and neohesperidin were measured by high performance liquid chromatography （HPLC）. SIMCA 14.1 software was used for cluster analysis of their shapes， sizes， and flavonoid contents， thus figuring out the similarities between the traditional and nontraditional medicinal varieties in character， size， and chemical components. Result:SRAP markers-based genetic relationship analysis effectively distinguished different Citri Reticulatae Semen varieties from each other. Some samples collected from the same or adjacent places exhibited a close genetic relationship and they shared high similarities in shape， size， and flavonoid content. However， the traditional medicinal Citri Reticulatae Semen was still quite different from most nontraditional medicinal varieties. Conclusion:The analysis of differences in genetic materials， appearance， character， and active ingredient content between the traditional and nontraditional medicinal varieties revealed that the equivalence<italic> </italic>of <italic>C.</italic> <italic>reticulata</italic> 'Ponkan' samples from some regions with the traditional medicinal variety was the largest， enabling them to be considered as the emerging medicinal variety.

Comparative transcriptome and proteome profiling of chlorophyll metabolism pathway in four types of Magnolia officinalis / 中国中药杂志

Magnolia officinalis is a traditional Chinese medicine,with many years of cultivating process, M. officinalis leaves show more differentiation types due to the exchange of seeds from different provenances. "Da Ao"(DA), "Xiao Ao"(XA), "Chuan Hou"(CH),and "Liu Ye"(LY)are the main types of M. officinalis in Sichuan province of China,and there were obvious differences in growth rate,chemical composition,leaf shape and leaf colour. This study selected different types of M. officinalis leaves(DA,XA,LY and CH)from Sichuan to determine their chlorophyll content. Transcriptomic level sequencing of different types of M. officinalis leaf tissues was by high-throughput sequencing analysis and proteomics used an integrated approach involving TMT labelling and LC-MS/MS to quantify the dynamic changes of the whole proteome of M. officinalis. The results showed that CH had the lowest chlorophyll content while DA had the highest chlorophyll content. Furthermore,transcriptome and proteomics results showed that chlorophyll synthesis pathway in DA glutamine-tRNA reductase,urinary porphyrins decarboxylase(UROD),oxygen-dependent protoporphyrin(ODCO),the original-Ⅲ oxidase protoporphyrin oxidase(PPO),magnesium chelating enzyme subunit ChlD,protoporphyrin magnesium Ⅸ monomethyl ester [oxidative] cyclase(MPPMC)were significantly higher than CH,XA and LY,consistent in the results of determination of chlorophyll content(chlorophyll content was highest of 37.56 mg·g~(-1) FW). Some rate-limiting enzymes related to the chlorophyll synthesis,such as ODCO,PPO and MPPMC were tested by Parallel Reaction Monitoring(PRM),and the results showed that the rate-limiting enzyme content in DA was higher than that in other three types. Therefore,based on the differences in leaf color of four types of M. officinalis,the research conducted a preliminary study on the chlorophyll metabolism pathway in leaves of different types of M. officinalis,and explored relevant genes and proteins causing leaf color differences from the molecular level,so as to lay a foundation for studying the differences in growth and development of different types of M. officinalis.

Analysis of Key Varieties and Rational Allocation of Traditional Chinese Medicine Resources Under COVID-19 Epidemic Situation / 中国实验方剂学杂志

Traditional Chinese medicine (TCM) plays an important role in the fight against coronavirus diseasef-2019 (COVID-19) epidemic. A total of 241 Chinese patent medicines and 242 prescriptions were recommended by the state and 26 provinces (autonomous regions and municipalities directly under the central government) for the prevention and treatment of COVID-19. A total of 53 varieties of commonly used medicinal materials were selected by analysis, of which 20 were common key varieties in medicinal materials of Chinese patent medicines and prescriptions, including Glycyrrhizae Radix et Rhizoma, Forsythiae Fructus, Pogostemonis Herba, etc. At the same time, some cold-quilt medicines and ethnic medicines also played an important role in the epidemic. By evaluating the supply and regeneration ability of the key varieties of TCM resources under the current COVID-19 epidemic situation, means of the source, regeneration cycle, medicinal parts, new production and market information of 53 kinds of TCM at present, it is suggested that the artificial cultivation of Glycyrrhizae Radix et Rhizoma and Paeoniae Radix Rubra can be strengthened, the development of Lonicerae Japonicae Flos, Isatidis Radix and other domestic medicinal materials can be controlled. In response to the change in market demand, the production variety structure and planting area of Chinese medicinal materials were timely adjusted to improve the quality standard and safety index of Chinese medicinal materials, and in order to provide ideas for the rational allocation of TCM resources and the development of Chinese medicinal materials industry under the epidemic situation.

Efficacy and safety of non-vitamin K antagonist versus vitamin K antagonist oral anticoagulants in the prevention and treatment of thrombotic disease in active cancer patients: a systematic review and meta-analysis of randomized controlled trials / 中华心血管病杂志

Object We aimed to compare the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonist (VKA) in the prevention and treatment of thrombotic diseases in patients with active cancer. Methods: To find randomized controlled trials (RCT) in which NOACs were compared VKAs in active cancer, we searched the electronic databases (PubMed, Web of Science and Clinical Trials) up to May 2019 and and languages restricted to Chinese and English. According to the screening strategy, two researchers independently screened and extracted literature, evaluated the quality of literature, the suitability of collected cross study data for analysis, and tested the heterogeneity. The relative risk (RR) and 95% confidence interval (95%CI) of major bleeding, clinically related non-major bleeding, VTE, stroke and all-cause mortality in active cancer patients with VTE, active cancer patients with non-valvular atrial fibrillation (NVAF) was calculated and the results were compared between NOAC with VKA. Results: A total of 9 RCTs were included, including 5 cancers with VTE (5/9) and 4 cancers with NVAF (4/9). A total of 5 867 patients were included. After excluding 1 818 (30.99%) patients with cancer history, 4 049 (68.86%) patients with active cancer were statistically analyzed. Among them, 2 278 (56.26%) received NOAC treatment, 1 771 patients (43.74%) received VKA treatment. The quality of the included documents was high (all scores were>5 points), and the data of each included document could be summarized and analyzed (P>0.05). The heterogeneity of main outcome events was very low (I2 = 0). In VTE patients with active cancer, NOACs were more effective in reducing recurrence of VTE （RR=0.55, 95%CI 0.36 -0.84; P = 0.005) and clinically related non-major bleeding (RR=0.77, 95%CI 0.60 -0.98; P = 0.03) than VKAs. In NVAF patients with active cancer, efficacy of NOACs and VKAs was similar in terms of reducing VTE, stroke, clinically related non-major bleeding, major bleeding and all-cause mortality events (P>0.05). Conclusions: For patients with active cancer accompanied by VTE, NOAC may has more advantages in efficacy and safety compared to VKA in the prevention and treatment of thrombotic diseases.

Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study / 中华医学杂志(英文版)

Background@#The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran.@*Methods@#A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.@*Results@#During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 109/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 109/L. For leukocyte counts < 6.75 × 109/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75 × 109/L, the HR (95% CI) was 1.28 (1.09–1.51).@*Conclusion@#This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.@*Clinical trial registration@#NCT02414035, https://clinicaltrials.gov.

Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study / 中华医学杂志(英文版)

BACKGROUND@#The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran.@*METHODS@#A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.@*RESULTS@#During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 10/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99-1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 10/L. For leukocyte counts < 6.75 × 10/L, the HR (95% CI) was 0.88 (0.69-1.13), and for leukocyte counts ≥ 6.75 × 10/L, the HR (95% CI) was 1.28 (1.09-1.51).@*CONCLUSION@#This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.@*CLINICAL TRIAL REGISTRATION@#NCT02414035, https://clinicaltrials.gov.

Compound traditional Chinese medicine in treatment of diabetes / 中国中药杂志

Diabetes is a chronic disorder of glucose metabolism characterized by elevated blood glucose levels. With the improvement in living standards and the changes in lifestyle,T2 DM incidence has a dramatic increase in the past decades,bringing a series of public health problems. In the research and development field of diabetic drugs,T1 DM drugs are mainly long-acting sustained-release insulin preparations,whereas T2 DM drugs mainly are based on single target. T2 DM drugs usually have a good anti-hyperglycemic effect,but with side effects for long-term administration. Therefore,the research and development of hypoglycemic drugs focus on formula drugs with multi-component,multi-target and multi-pathway effects. In the similar principle of action,traditional Chinese medicine formula has achieved a good efficacy in the treatment of diabetes,with mild anti-hyperglycemic effects and multiple-component synergistic effects in intervening the pathogenesis of diabetes,including additive effect,synergy effect and toxicity scattering effect. This article mainly reviews clinical trials and mechanisms of action of traditional Chinese medicine formula for the treatment of diabetes,so as to provide a reference to the rational and effective clinical application of traditional Chinese medicine formula in treating diabetes.

Cloning and expression analysis of MYB transcription factor genes in safflower / 药学学报

Safflower is a dried flower of the annual herbaceous plant safflower (Carthamus tinctorius L.). As a traditional Chinese medicine, it was widely used in the regulation of blood circulation. Flavonoids are the main active ingredients in safflower. MYB transcription factors are involved in the regulation of flavonoids. The cloning and expression analysis of MYB transcription factor genes in safflower is of great significance, not only for clarifying the regulation mechanism of flavonoids biosynthesis in safflower, but also for the artificial regulation of flavonoid biosynthesis in safflower. Based on the transcriptome data, we used iTAK to annotate the MYB transcription factors in safflower. The MYB transcription factors were cloned and their sequences were analyzed. Besides, their expressions were analyzed by a Real-time PCR. In the experiment, eight long fragment MYB transcription factors were screened and six MYB transcription factors was successfully cloned, named CtMYB-TF1, CtMYB-TF2, CtMYB-TF4, CtMYB-TF5, CtMYB-TF6 and CtMYB-TF7, respectively. The six MYB transcription factors had the core domain of MYB transcription factor family, and evolutionary analysis showed that the CtMYB-TF7 transcription factor was closely related to the factors AtMYBL2 and AtMYB12. Expression analysis showed that the expression of CtMYB-TF5, CtMYB-TF6 and CtMYB-TF7 was low in roots, stems and leaves, and was high in the flower. The results provide a foundation for study of mechanism of molecular regulation of safflower flavonoids.

Effect of exogenous GA₃ and DPC on active components of Lonicera japonica and its mechanism / 中国中药杂志

To reveal the effect of plant growth regulator GA₃ and DPC on the active components and its possible mechanism of Lonicera japonica. GA and DPC were applied at the stage of flower bud differentiation, and the content of active ingredients was measured by LC-MS-MS, the content of endogenous hormones were measured by ELISA, and the expression of key enzyme enes expression was determined by qRT-PCR. The level of endogenous hormone GA₃, IAA, ZR, DHZR and iPA in the GA treatment group was significantly improved, the expression of C4H1, C4H2, 4CL1 and HQT2 were also significantly increased. The content of chlorogenic acid, luteolin, luteoloside, isoquercetin and caffeic acid increased significantly. Spraying DPC did not affect or inhibit the accumulation of active components of L. japonica. Spraying GA can increase the content of endogenous GA₃, thus enhance the expression of C4H1, C4H2, 4CL1 and HQT2, and then increase the content of chlorogenic acid and luteolin.

Correlation between accumulation of flavoneand expression of functional genes in Carthamus tinctorius / 中国中药杂志

The average yield of safflower blooming from 1 to 7 day was recorded and calculated, HPLC was used to detect the percentage composition of HYSA,quercetin,naringenin and kaempferol, and the real-time PCR was used to analyze the expression of chs and chi. The average yield,percentage composition of HYSA and naringenin as well as functional genes' expression presented similar trends. The average yield reached the highest peak at the third day, showing highpositive correlation with the contents of HYSA (r=0.756,P<0.05), and significant correlation with the expression of chi (r=0.892,P<0.01). The contents of naringenin showed a high positive correlation with the expression of chs(r=0.766,P<0.05). The study provides a theory basis for the composition and regulation mechanism of the flavonoid constituents and lays foundation for molecular mechanisms which lead to the difference of quality in C. tinctorius.

Safflower's origin and changes of producing areas / 中国中药杂志

Human's application of safflower (Carthamus tinctorius) has a long history, but the origin remains unclear. Safflower was introduced into China for traditional Chinese medicine, and Sichuan was major producing area. However, in recent years, the main producing area is in Xinjiang province, in contrast Sichuan safflower is difficult to find. By reading relevant document literature and the production and marketing information of safflower, and having field investigation in the main producing areas, the origin of safflower and the reasons of producing areas' changes were explored. The origin of safflower is considered as the Fertile Crescent in reasonably. The change of producing areas in China is effected by the factors of natural environment and society. The suitability of producing areas and quality of safflower still need to study further.

RITA combined with temozolomide inhibits the proliferation of human glioblastoma U87 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism.</p><p><b>METHODS</b>Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining.</p><p><b>RESULTS</b>MTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (P<0.01) and TMZ (P=0.000) alone. At the doses above 5 µmol/L, the combined treatments with RITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment.</p><p><b>CONCLUSION</b>RITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.</p>

Toxic potential of palytoxin / 华中科技大学学报（医学）（英德文版）

This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na(+)/K(+)-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.

Mutation analysis and first-trimester prenatal diagnosis for a Chinese family with hidrotic ectodermal dysplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze GJB6 gene mutations in a Chinese family with hidrotic ectodermal dysplasia and to provide first-trimester prenatal diagnosis for a fetus.</p><p><b>METHODS</b>Mutation scanning was carried out with PCR and bilateral direct sequencing in 2 affected and 6 unaffected individuals from the family. After the mutation was confirmed, prenatal diagnosis was performed on chorionic villi samples obtained at 11th gestational week.</p><p><b>RESULTS</b>A heterozygous missense mutation c.31G>A of the GJB6 gene was discovered in all of the patients, which has led to substitution of glycine by arginine at codon 11 (p.G11R) at the N-terminal of the GJB6 protein. Prenatal diagnosis indicated that the fetus had also carried the same p.G11R mutation. Following termination of the pregnancy, analysis of the aborted tissues was consistent with prenatal diagnosis.</p><p><b>CONCLUSION</b>The missense mutation c.31G>A(p.G11R) of the GJB6 gene probably underlies the disease in this family. Prenatal diagnosis with DNA sequencing can facilitate genetic counseling of this family.</p>

Evaluation of the key indicators in the pituitary-target gland axes in the animal model with shenyang deficiency syndrome using factor analysis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the key indicators in the pituitary-target gland axes in the animal model of Shen-yang deficiency syndrome (SYDS).</p><p><b>METHODS</b>The 8 biological indicators [thyroid stimulating hormone (TSH), 3, 3', 5-triiodothyronine (T3), thyroxine (T4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), adrenocorticotropic hormone (ACTH), and cortisol (CORT)] in the pituitary-target gland axes were grouped using factor analysis. Then the sensitivity of every indicator was calculated according to the sensitivity function defined in this paper, so as to find all the most sensitive indicators in every group as key indicators of SYDS.</p><p><b>RESULTS</b>The key indicators in the early period of SYDS were T, LH, T4, and CORT. The key indicators in the middle period were LH,T, CORT, and ACTH. The key indicators in the late period were LH, T, CORT, and FSH.</p><p><b>CONCLUSIONS</b>T, LH, and CORT were the common key indicators of the three periods, and other different key indicator of SYDS in the early, middle and late period were T4, ACTH, and FSH respectively, which changed from the thyroid axis to the adrenal axis and then to the gonadal axis as the period changed. The key indicators in the late period were mainly in the gonadal axis, showing gonadal dysfunction in the late period.</p>

Detection of ED1 gene mutations in six pedigrees with hypohidrotic ectodermal dysplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutations of ED1 gene in six pedigrees with hypohidrotic ectodermal dysplasia (HED), and to provide genetic counseling and prenatal diagnosis.</p><p><b>METHODS</b>Eight coding exons of ED1 gene of patients with clinically diagnosed HED and their relatives were amplified by polymerase chain reaction (PCR). The products were further analyzed by direct sequencing.</p><p><b>RESULTS</b>Various mutations of ED1 gene were detected, which included R153C, A349T, G299S, A349T and X392Q. Heterozygous double peaks at the same position were found in female carriers. Deletion of exon 9 was detected in one pedigree. R153C, X392Q and deletion of exon 9 were first identified in ethnic Han Chinese.</p><p><b>CONCLUSION</b>The identified mutations of ED1 gene may be responsible for the disease. Genetic counseling, prenatal diagnosis and carrier screening are now available for these families.</p>