Cell-penetrating peptide (CPP) is a kind of small molecular peptide which can pass through a variety of cell membranes. It can carry bioactive macromolecules into cells. Due to lacking of tissue-selecting and targeting behavior, the application of CPP in the field of tumor treatment is limited. Activatable cell- penetrating peptide (ACPP) has brought the dawn to the application of CPP. This review mainly introduces the applications of ACPP in the targeting antitumor drug delivery which was designed based on the differences between tumor microenvironment and normal tissues as well as the exogenous physical stimulation.

Objective To investigate and analyze TCM syndrome characteristics, impact factors and internal relationship among the factors of mental fatigue of university students. A preliminary understanding of mental fatigue situation of university students and prevent diseases was acquired in advance. Methods 100 students were randomly selected in Beijing University of Chinese Medicine, of whom 40 were undergraduate students and 60 were post-graduate students. Mental fatigue questionnaire was used to investigate mental fatigue situation for students, and TCM constitution scale was applied to collect TCM syndromes. A body energy survey was also conducted. Results In undergraduate and post-graduate students, the mental fatigue rate was relatively higher, both of them were over 50%of the total numbers, 57.5%(23/40)、61.7%(37/60) respectively. For the fatigue levels distribution in these two groups, the ratios of slight mental fatigue (undergraduate:52.5%;post-graduate:56.67%) were both higher than those of severe mental fatigue (undergraduate:5%;post-graduate:5%). In the undergraduate group, the top three biased constitutions among mental fatigue students were yang deficiency (7 out of 23:30.43%), qi deficiency (3 out of 23:13.04%) and dampness-heat (3 out of 23:13.04%). In the post-graduate group, the top three biased constitutions were yang deficiency (11 out of 37:29.73%), qi deficiency (6 out of 37: 16.22%) and dampness-heat (5 out of 37: 13.51%). Conclusion It is easier for university students with biased constitution to suffer from mental fatigue, mostly with yang deficiency, qi deficiency and dampness-heat constitution.

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.

To evaluate the value of serum human epididymis protein 4(HE4),cancer embryonic antigen(CEA), carbohydrate antigen(CA125,CA19-9,CA153),alpha fetoprotein(AFP) and β-human chorionic gonadotrophin (β-HCG) in ovarian cancer early diagnosis.Methods:Abbott Architect i2000SR was used to detect the levels of preoperative serum tumor markers (n=7) in ovarian cancer group,benign ovarian tumor group and the normal control (each n=60).Results:The levels of serum HE4,CA125, CA199,CEA,CA153,AFP and β-HCG in ovarian cancer group were markedly higher than the benign ovarian tumor group and the control group.There was statistically significant difference ( P<0.05 ).The diagnosis of ovarian cancer tumor markers were high specificity,but sensitivity was not high except HE4 (76.67%) and CA125 (68.33%).With Youden Index,the area under curve of ROC,the HE4 was demonstrated higher specificity ,sensitivity and accuracy.There was also medium diagnostic value of CA 125 ,CA199 and CEA for ovarian cancer.The sensitivity of ovarian cancer diagnosis is raised by combined assay with serum tumor marker ,but the specificity would be reduced accordingly.HE4, CA125, CA199 and CEA combined detection is considered the best.Conclusion:CA153,AFP and β-HCG have lowered diagnosis for ovarian cancer.HE4, CA125, CA199 and CEA combined detection could significantly improve specificity ,sensitivity and accuracy in the early diagnosis of ovarian cancer.

Objective To study and compare the molecular mechanism of SiniSan (Cold-Limbs Powder) and Suanzaoren Tang (Spine Date Seed Decoction) in treatment of insomnia based on network pharmacology method.Methods A database of active compounds of Sini San and Suanzaoren Tang was established through searching the databases of Chinese medicinal compounds including traditional Chinese medicinal system pharmacology platform (TCMSP) , and the predictive analysis of the compounds was conducted by using machine learning algorithm.Based on the analyses of KEGG pathway, gene ontology (GO) enrichment and disease association of therapeutic target database (TTD) , Cytoscape software was used to construct complex network of active constituent-target-disease and topological analysis of the pharmacological mechanisms of Sini San and Suanzaoren Tang.Results There were 145 active constituents obtained from Sini San and among them saikoside and kaempferol had higher binding activities.There were 1 306 target proteins obtained and among them22 were significantly correlated to diseases, and 49 significant KEGG pathways and 72 significant GO enrichment pathways obtained from Sini San.There were 139 active constituents obtained from Suanzaoren Tang and among them jujuboside and timosaponin had higher binding activities.There were 1 386 target proteins, 52 significant KEGG pathways and 84 significant GO enrichment pathways obtained from Suanzaoren Tang.Conclusion The potential network pharmacological mechanisms and active constituents of Sini San and Suanzaoren Tang in insomnia treatment are studied at the molecular biology level through complex network graph calculation and bioinformatics analysis.The purpose is to provide new ideas for further revealing the mechanism of treating insomnia with Chinese medicinal based on principle of different treatments for the same disease.

Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide (GICP), was previously reported as a ligand for the VAV3 protein (a Rho-GTPase guanine nucleotide exchange factor), which is mainly expressed on glioma cells; the stabilized heptapeptide A7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), and has demonstrated good neovasculature-targeting ability. By linking A7R and GICP, a multi-receptor targeting molecule was obtained. The stability of these three peptides was evaluated and their targeting efficiency on tumor-related cells and models was compared. The ability of these peptides to cross the blood--tumor barrier (BTB) was also determined. The results indicate that the coupled Y-shaped peptide A7R-GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide.

Objective To investigate the effects of Tianxiang capsule on Neurotransmitters and Hormone Level of rats with motion sickness. Methods Male SD rats were randomly divided into six groups, including blank control group, model control group, positive drug control group, low-dose, mid-dose and high-dose Tianxiang capsule groups with the method of random digital table, and every group had 10 mice. Except the normal group, the rats in the other groups were intragastrically pre-administered for 1 hour, and the low, medium and high doses of Tianxiang capsule were 0.91, 1.82, 3.64 g/kg, the positive drug control group was given scopolamine 1 mg/kg, and then the rat motion sickness model was induced by a rotary stimulation device. After the modeling, the feces, urine, standing hair, trembling were immediately observed and recorded, and the halo response index of the rats was calculated. The blood from the heart puncture was taken and the vestibular nucleus were put on the ice. Then, the content of histamine (HIS) in the vestibular nucleus and plasma was detected by ELISA. The expression of plasma cortisol (Cort) and arginine vasopressin (AVP) were measured by radioimmunoassay. Results Compared with the model control group, the motion sickness index of rats with low, medium and high doses of Tianxiang capsule (6.56 ± 2.16, 6.10 ± 1.35, 4.46 ± 2.50 vs. 8.90 ± 2.61) significantly decreased (P<0.05 or P<0.01). The HIS content in the vestibular nucleus (12.70 ± 3.86 μg/L, 11.45 ± 1.57 μg/L, 10.02 ± 1.30 μg/L vs. 17.50 ± 4.82 μg/L) significantly decreased (P<0.05 or P<0.01). The plasma content of HIS (4.24 ± 1.75 μg/L vs. 7.69 ± 3.06 μg/L), Cort (286.90 ± 8.72 ng/ml vs. 329.26 ± 29.04 ng/ml) and AVP (16.54 ± 2.48 pg/ml vs. 22.35 ± 3.08 pg/ml) in the high doses of Tianxiang capsule significantly decreased (P<0.05 or P<0.01). Conclusions The Tianxiang capsule could effectively reduce the motion sickness index of rats with motion sicknes, which might be related to the down-regulation of HIS in Vestibule Nucleus and HIS, Cort and AVP in plasma.

ObjectiveThe research focuses on developing modeling and evaluation methodologies for an animal model exhibiting spleen deficiency and dampness excess syndrome， with the aim of standardizing such animal models for future reference. MethodsBy conducting a literature search on animal models of spleen deficiency and dampness excess syndrome， relevant publications meeting inclusion and exclusion criteria will be identified based on publication date， data source， types of diseases involved， animal characteristics， modeling methods， modeling duration， macroscopic syndrome assessment indicators， macroscopic quantification indicators， laboratory testing parameters， intervention approaches， positive controls and application context. A database will be established to facilitate the extraction of this information for quantitative analysis， statistical evaluation， and visual representation. ResultsA total of 137 literature articles meeting the standards have been included in the research. The primary animal species used in animal models of spleen deficiency and dampness excess are SD rats. Modeling methods include single-factor， dual-factor composite， and triple-factor composite methods， with various models widely applied in validation of pharmacological effects and mechanistic explorations. Evaluation indices of animal models for spleen deficiency and dampness excess primarily consist of macroscopic syndrome evaluation indicators and macroscopic quantitative indicators. Laboratory testing indicators are mostly related to research areas such as fluid metabolism and gastrointestinal function. The most commonly studied herbal formulas currently include Shenling Baizhu San and Pingwei San， with natural recovery and the use of the western medicine metronidazole as the most frequently used positive controls. ConclusionThe application of animal models for spleen deficiency and dampness excess is gradually increasing， with various modeling methods already simulating the typical characteristics of this syndrome pattern. However， there are still many areas that are worth contemplating and improving. This study aims to provide reference and ideas for the standardization of symptom names in animal models of spleen deficiency and dampness excess， as well as for the improvement of model construction and evaluation systems.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.