cAMP response element binding protein (CREB) is an eukaryotic intranuclear protein widely expressed in a variety of organs, and its activation increases the transcriptional activity of downstream genes and promotes the expression of related genes. The neuronal function of CREB is related to many intracellular processes, such as proliferation, differentiation, survival, long-term synaptic potentials, neurogenesis and neuronal plasticity. Increasing evidence has demonstrated that CREB plays an important role in the stroke development and therefore, it may serve as a potential target for stroke therapy. Since some herbal medicines as well as their active ingredients regulate the CREB signaling, this article will summarize the role of CREB signaling pathway in stroke pathophysiology. The research progress of traditional Chinese medicine and its active ingredients modulating CREB activity will also be discussed, with the aim of providing the basis and reference for the future research and development of natural medicines against stroke.

According to the requirements of the regulatory authorities, degree of modification (DP) should be included in the characterisation of the PEGylated protein drug substance, and is one of the critical quality attributes for quality control. In this study, based on the fundamental assumption that the refractive index (RI) signal and the ultraviolet (UV) signal of PEGylated protein are equal to the sum of the corresponding signal produced by the polyethylene glycol (PEG) and protein parts of the conjugates in their uncoupled state, we developed a method to determine the DP of PEGylated recombinant human growth hormone (inpegsomatropin). In this method, 20 μL of 1 mg·mL^-1 human growth hormone (hGH) standard, 2 mg·mL^-1 PEG reference substance and 1 mg·mL^-1 drug substance solution were each injected to size exclusion chromatographic (SEC) column for separation, detected with ultraviolet and refractive index (UV-RI) detectors in series. Finally, the DP was calculated as the formula derived from the fundamental assumption. The developed SEC-UV-RI method showed good specificity, repeatability (RSD = 0.63%, n = 9) and accuracy, with a recovery of 100.0%, compared with the result obtained from the simultaneously established classical acid hydrolysis method, demonstrating pretty handleability and accessibility, and is appropriate for quality control test of DP for this drug substance.

In recent years, more and more forensic genetics laboratories have begun to apply massively parallel sequencing (MPS) technology, that is, next-generation sequencing (NGS) technology, to detect common forensic genetic markers, including short tandem repeat (STR), single nucleotide polymorphism (SNP), the control region or whole genome of mitochondrial DNA (mtDNA), as well as messenger RNA (mRNA), etc., for forensic practice, such as individual identification, kinship analysis, ancestry inference and body fluid identification. As the most widely used genetic marker in forensic genetics, STR is currently mainly detected by capillary electrophoresis (CE) platform. Compared with CE platform, MPS technology has the advantages of simultaneous detection of a large number of genetic markers, massively parallel detection of samples, the polymorphism of sequence detected by NGS makes STR have the advantages of higher resolution and system efficiency. However, MPS technology is expensive, there is no uniform standard so far, and there are problems such as how to integrate MPS-STR data with the existing CE-STR database. This review summarizes the current status of the application of MPS technology in the detection of STR genetic markers in forensic genetics, puts forward the main problems that need to be solved urgently, and prospects the application prospect of this technology in forensic genetics.
DNA Fingerprinting/methods* ; Forensic Genetics/methods* ; Genetic Markers ; High-Throughput Nucleotide Sequencing/methods* ; Microsatellite Repeats/genetics* ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Technology

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

Objective To explore the sensitivity of Culex pipiens pallens to common chemical insecticides in the southwestern region of Shandong Province, so as to provide a theoretical basis for the development of reasonable and effective mosquito control measures. Methods The resistance of Cx. pipiens pallens larvae to 5 chemical insecticides, such as cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate were tested by using the WHO biological test method in 2018, and the co-toxicity coefficients after compounding the above-mentioned insecticides were tested by using a drug compounding method. Results The resistance indexes of Cx. pipiens pallens to cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate in 3 cities were 144.43–557.54, 118.17–445.33, 6.44–19.00, 2.37–8.10, and 0.88–2.98, respectively, and expect the difference between the DDVP resistances of Cx. pipiens pallens in Jining City and Heze City was not statistically significant (P > 0.05), all the other differences were statistically significant (all P < 0.05). The synergistic coefficients of cypermethrin + DDVP, cypermethrin + propoxur, DDVP + acetofenate, and propoxur + acetofenate were 199.58 – 456.95, 190.56 – 292.37, 123.32 – 319.24, and 192.31 – 367.32, respectively. The lower synergism was observed by using the mixture of DDVP + propoxur (synergistic coefficient: 99.87–108.36) . Conclusions After decades of chemical control, Cx. pipiens pallens in the southwestern region of Shandong Province has produced different degrees of resistance to common chemical insecticides. Therefore, comprehensive control measures should be taken to control mosquito breeding and prevent the development of insecticide resistance.

Objective To investigate the changes of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and omentin-1 in patients with H-type hypertension complicated with acute ischemic stroke, and to analyze the correlation of sLOX-1 and omentin-1 levels with the severity and prognosis of the disease.Methods Totally 136 patients with H-type hypertension complicated with acute ischemic stroke from February2017 to May 2018 were selected as observation group, and 136 non-acute ischemic stroke patients with H-type hypertension in the same period as the control group. The patients of observation group were divided into mild, moderate and severe sub-groups according to NIHSS score, and they were also divided into good prognosis group and poor prognosis group based on modified RANKIN scale (mRS) score. The serum sLOX-1 and omentin-1 levels were detected, and the correlation of sLOX-1 and omentin-1 levels with severity and prognosis of disease was analyzed. Results The serum sLOX-1 level of the observation group was higher, but the serum omentin-1 level lower than that of control group (P < 0.05). With the severity of the disease, the serum sLOX-1 level increased, but the serum omentin-1 level decreased (P < 0.05). The serum sLOX-1 level of good prognosis group was significantly lower, whereas the serum omentin-1 level significantly higher than that of poor prognosis group (P < 0.05). sLOX-1 was positively correlated with NIHSS score and mRS score, while omentin-1 was negatively correlated with NIHSS score and mRS score (P < 0.05). Conclusions The levels of serum sLOX-1 and omentin-1 are closely related to the severity and prognosis of patients with H-type hypertension complicated with acute ischemic stroke, which could be used as markers for evaluating the severity and prognosis of the patients.

Objective:To investigate the role of IL-17D to regulate the recruitment of lung NK cells and the effects of Astragalus membranaceus on IL-17D.Methods:The lung metastasis of tumor model was established by injecting B16 melanoma cells through caudal vein.After being treated with IL-17D or Astragalus membranaceus respectively,the expression of IL-17D and NK cells in lung was detected by flow cytometry and RT-PCR.Results:The production of IL-17D and the content of NK cells in the lung tumor me-tastasis model were dramatically decreased.After treatment with IL-17D,the content of NK cells in lung was significantly increased and the lung tumor foci were decreased.Along with up-regulated recruitments of NK cells,CXCL9 and IL-15,which support NK cell recruitments and maintain survival,were significantly increased.Astragalus inhibited lung tumor developments in lung by increasing the IL-17D expression and up-regulated the lung NK cell content.Conclusion: IL-17D can regulate the lung recruitment of NK cells.Astragalus mongholicus can enhance the capacity of NK cell recruitment and promote anti-tumor immune effects by up-regulating the expression of IL-17D.

Objective To investigate the diagnostic value of sharp kernel reconstructed images for calcified plaque coronary artery stenosis with a dual-source CT.Methods 42 patients with suspected coronary disease underwent dual-source coronary computed tomography angiography (CCTA) and coronary angiography (CAG).The CCTA images were respectively reconstructed by smooth kernel (I26f) and sharp kernel (I46f) reconstruction.The image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured,and then the calcified plaque noise of two groups reconstructed image was scored subjectively.A total of 56 vascular stenoses that caused by calcification were taken as the research object,according to the results of CAG as a golden standard.The ROC curves of two groups were drawn with moderate stenosis (more than or equal to 50%) and severe stenosis (more than or equal to 75%), and the corresponding sensitivity, specificity, and optimal threshold were obtained.Results The images of I46f group had higher noise [I46f:(45.43±9.00) HU;I26f:(31.43±5.55) HU;t=-8.58,P=0.000],lower SNR [I46f:(10.26±2.09) HU;I26f:(14.86±3.53) HU;t=7.28,P=0.000] and lower CNR[I46f:(14.04±4.51) HU;I26f:(20.80±7.18) HU;t=5.17,P=0.000],but the subjective scoring of calcified plaque of I46f group was better than that of I26f group(I46f:2.33±0.75;I26f:1.64±0.70,Z=-4.61,P=0.000).The ROC curves of two groups: with moderate stenosis(≥50%),area under the I46f curve(0.946) was larger than that of I26f group (0.935);to diagnose with the reconstructed image of group I46f,the optimal threshold was 55%,the specificity was 95.0%,and sensitivity was 88.9%;and for I26f group,the optimal threshold was 65%, the specificity was 90%, and sensitivity was 88.9%.With severe stenosis(≥75%), area under the I46f curve (0.927) was slightly larger than that of I26f group (0.924);to diagnose with the reconstructed image of group I46f,the optimal threshold was 77.5%,the specificity was 79.1%,and sensitivity was 92.3%;for I26f group, the optimal threshold was 85%, the specificity was 74.4%,and the sensitivity was 100%.Conclusion The I46f reconstruction image of dual-source CT has more advantageous than the I26f reconstruction image,and it is a better way to diagnosethe calcified coronary stenosis.

Acute respiratory distress syndrome(ARDS)and acute lung injury are grave syndromes associated with high morbidity of the mortality.Currently,the criteria for the classification of the severity of ARDS are the PaO 2/FiO2values, while OI,S/F and OSI values are also used as ancillary diagnostic and grading criteria for ARDS.In this review,we sum-marize the effects of four indicators on the diagnosis and severity of ARDS patients,their respective strengths and weaknes-ses,and predit the future development of the classification of severity of ARDS.