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.

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.

Tumor-infiltrating lymphocytes (TILs) are a heterogeneous subset of lymphocytes, mainly T cells, present in tumor parenchyma and stroma. After being digested and isolated from tumor tissue and then cultured in vitro for activation and multiplication, it can be infused back into the patient's body to kill tumor cells. TILs have the advantages of high diversity of TCR, excellent ability to infiltrate into tumor sites, and low toxicity and are considered promising for the treatment of malignant solid tumors. At present, TIL therapy has been tested as a second-line treatment in a variety of solid tumors and has achieved preliminary results. Although there is still no clinical cohort report on the application of TILs in biliary tract cancer (BTC), recent clinical reports on multiple cancers have provided information on the efficacy of TIL therapy in a small number of BTC patients, which preliminarily confirmed the safety and efficacy of TIL therapy. However, since BTC is generally considered an immunologically repulsive tumor in which most effector T cells are sequestered at the tumor edge, the antitumor effect of TILs in BTC remains difficult to predict. Combination therapy with different anti-tumor methods and the development of new techniques to modify cells to enhance the anti-tumor ability of TILs are possible directions for breakthrough in the future.

Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.

Platform method is a modeling method that forces experimental animals to stand on the platforms for a long time without rest by taking advantage of the rodent's fear of water. The application time and node of platform method in model construction can be adjusted according to the needs of different types of animal models. At present， the research hotspot of platform method focuses on constructing animal models of sleep deprivation， anxiety and depression and other mental diseases as well as fatigue. In recent years， with the development of the modernization of traditional Chinese medicine （TCM）， this method has been gradually applied to the study of TCM syndrome model and TCM disease and syndrome combination model with "heart"，"liver" and "spleen" as the centers. Due to the extensive application of platform method and the diversity of modeling diseases， there is still a lack of systematic discussion on this method as the core. This paper systematically summarized the research in China and abroad and explored the application of platform method in animal models of human diseases from three dimensions： its development process， current application and problems and future development. In addition， through the analysis of the research hotspots on sleep deprivation， mental diseases， fatigue， TCM syndrome model and TCM disease and syndrome combination model，the ideas and specific applications of platform method in construction of various animal models were discussed. This paper was expected to provide reference for researchers and promote further exploration and research of this modeling method.