1.Decoy receptor 3:A novel target for gene therapy of cancer
Shenghang ZHANG ; Xiaopeng LAN
Journal of Medical Postgraduates 2003;0(03):-
Decoy receptor 3(DcR3),also known as tumor necrosis factor receptor 6B(TNFR6B) or TR6,is a newly discovered member of the tumor necrosis receptor superfamily,an apoptosis-prohibiting protein,which can both inhibit the apoptosis and promote the immunity escape of tumor cells.Recent researches have shown that DcR3 is expressed selectively in most human common tumors but not in normal adult tissue,and its up-regulation may predict the malignancy and prognosis of tumors.As a molecular marker of tumor,the high expression of DcR3 in the body fluid can help tumor detection and therapy monitoring.This novel biological technique can be used to inhibit the expression of the DcR3 gene and induce the apoptosis of tumor cells.
2.Heart rate turbulence phenomenon and metoprolol intervention effect in patients with essential hyper-tension
Leiyi ZHANG ; Shenghang LIU ; Xiaofang SUI
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(2):224-226
Heart rate turbulence (HRT)can Well reflect autonomic function.There usually exist different degrees of autonomic impairment in patients With hypertension.As a selectiveβ1 receptor blocker,metoprolol can not only de-crease patients' blood pressure,but also inhibit sympathetic activity,improve vagal activity and HRT in these pa-tients.This article made folloWing overvieW on HRT phenomenon and metoprolol intervention effect in patients With hypertension.
3.Research progress of static magnetic field targeting drug delivery system in tumor diagnosis and therapy
Huanhuan LYU ; Dandan DONG ; Jiancheng YANG ; Shenghang WANG ; Liangfu ZHOU ; Ge ZHANG ; Peng SHANG
International Journal of Biomedical Engineering 2017;40(2):65-70
Chemotherapy is one of the traditional tumors treatment solutions.Chemotherapy has the feature of tissue non-specificity,which can cause side effects on normal cells while inhibiting tumor cell growth.Magnetic targeting drug delivery system (MTDDS) employs biocompatible and stable magnetic nanoparticles (MNP) as drug carries to transport and accumulate anticancer drugs to the specific tumor tissues under the guidance of external magnetic field.This technology not only improves the efficiency of drug delivery and antitumor activity,but also reduces the drug dosage and side effects.The properties of drug-loaded MNPs and the applied external magnetic field are the main factors that affecting the MNPs targeting to the tumor tissues.The effectiveness of the targeted delivery of the drug-loaded magnetic nanoparticles mainly depends on the form and strength of the magnetic field at the target site.That is,whether there is sufficient strength to attract and retain NMPs,and to promote antitumor drug release at the tumor region.In this paper,the research progress of static magnetic field targeting drug delivery system in tumor diagnosis and therapy was summarized,which can provide some basic information for the relative scientific researches.
4.The construction of a peripheral blood qualitative transcriptional signature for the diagnosis of active tuberculosis
Saijun MA ; Kun CHEN ; Sheng LIU ; Tianyu LIN ; Shenghang ZHANG ; Huxing CHEN
Chinese Journal of Preventive Medicine 2024;58(11):1651-1658
Objective:To construct a signature for identifying active tuberculosis (TB) based on the relative expression orderings (REOs) of gene expression within a single sample.Methods:Using peripheral whole blood samples from 75 active TB and 69 latently infected individuals from four datasets as the training set, and highly stable REO patterns were extracted from the gene expression profile of the two groups of samples. Then, the gene pairs that reversed the REO pattern between the two groups were selected, and each gene pair was ranked in descending order based on their reversal degree. Finally, the top k gene pairs with the highest classification accuracy were selected as the signature for independent dataset validation. Results:A signature composed of seven gene pairs, denoted as 7-GPS, was constructed from the training set. The accuracy rate for 7-GPS to distinguish active TB from latently infected samples was 88.89%, and the accuracy rate for distinguishing active TB from normal samples was 90.09%. In the mixed validation data from different detection platforms, the AUC value for distinguishing active TB from latently infected samples was 0.914 (95% CI: 0.881-0.948), and the AUC value for distinguishing active TB from normal samples was 0.934 (95% CI: 0.904-0.964). In addition, the four genes ETV7, BATF2, ANKRD22 and CARD17P from this signature tended to be highly expressed in peripheral blood samples of active TB, and their expression values were significantly related to the duration of anti-tuberculosis treatment in clinical. Conclusion:The 7-GPS signature is robust and suitable for individualized analysis of a single peripheral blood sample. It has certain clinical application potential.
5.The construction of a peripheral blood qualitative transcriptional signature for the diagnosis of active tuberculosis
Saijun MA ; Kun CHEN ; Sheng LIU ; Tianyu LIN ; Shenghang ZHANG ; Huxing CHEN
Chinese Journal of Preventive Medicine 2024;58(11):1651-1658
Objective:To construct a signature for identifying active tuberculosis (TB) based on the relative expression orderings (REOs) of gene expression within a single sample.Methods:Using peripheral whole blood samples from 75 active TB and 69 latently infected individuals from four datasets as the training set, and highly stable REO patterns were extracted from the gene expression profile of the two groups of samples. Then, the gene pairs that reversed the REO pattern between the two groups were selected, and each gene pair was ranked in descending order based on their reversal degree. Finally, the top k gene pairs with the highest classification accuracy were selected as the signature for independent dataset validation. Results:A signature composed of seven gene pairs, denoted as 7-GPS, was constructed from the training set. The accuracy rate for 7-GPS to distinguish active TB from latently infected samples was 88.89%, and the accuracy rate for distinguishing active TB from normal samples was 90.09%. In the mixed validation data from different detection platforms, the AUC value for distinguishing active TB from latently infected samples was 0.914 (95% CI: 0.881-0.948), and the AUC value for distinguishing active TB from normal samples was 0.934 (95% CI: 0.904-0.964). In addition, the four genes ETV7, BATF2, ANKRD22 and CARD17P from this signature tended to be highly expressed in peripheral blood samples of active TB, and their expression values were significantly related to the duration of anti-tuberculosis treatment in clinical. Conclusion:The 7-GPS signature is robust and suitable for individualized analysis of a single peripheral blood sample. It has certain clinical application potential.
6.A colorimetric biosensor based on aptamer-gold nanoparticles for rapid detection of Lp-PLA2
Huimin NIU ; Yijun SHE ; Gongxu LIU ; Shuqian QIU ; Juan CHEN ; Shenghang ZHANG
Chinese Journal of Laboratory Medicine 2024;47(8):936-944
Objective:The DNA aptamers of lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vasculitis, were screened and a visual detection method using unlabeled nucleic acid aptamer-gold nanoparticle (AuNP) probe was established.Method:Lp-PLA2 aptamers were screened through 8 cycles of incubation binding, ssDNA isolation, PCR amplification and single strand recovery by the magnetic bead fixation SELEX technique. The affinity and specificity of the aptamers were validated using surface plasmon resonance technology and flow cytometry, and the secondary structure of the aptamer and its three-dimensional molecular docking with the target protein were simulated by computer software. Subsequently, aptamer-AuNP complex was prepared, and the color change was caused by salt-induced condensation of the AuNP solution by target competitive binding. Then, the target concentration was detected by measuring the absorbance of the solution with a spectrophotometer. The linear relationship between the sample absorbance and concentration of Lp-PLA2 were established under the optimal determine conditions.Results:Three Lp-PLA2 aptamers B76-2, B76-4 and B76-5 with high affinity and strong specificity were obtained, and the dissociation constants were 1.07, 1.26 and 1.75 nmol/L, respectively. Then AuNP colorimetric sensing method based on B76-2 aptamer was successfully constructed. The linear range and detection limit of Lp-PLA2 were 20-500 ng/ml and 78 ng/ml, respectively, and the reaction time was 30 min, which could specifically distinguish the target from other thrombotic markers such as thrombin and myeloperoxidase.Conclusion:A simple, rapid and specific visual detection method for visually detecting Lp-PLA2 was established by using aptamer-AuNP colorimetric assay.
7.Correlation Study on Expression of PD-1 and PD-L1 in Non-small Cell Lung Cancer and Epidermal Growth Factor Receptor Mutations.
Ling JIANG ; Zhiyi LIN ; Na LI ; Jinfang JIANG ; Cengceng LU ; Shenghang DU ; Jun ZHANG ; Yuanyuan WANG ; Jun CHEN ; Ping GONG
Chinese Journal of Lung Cancer 2021;24(9):623-631
BACKGROUND:
The treatment mode of lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for patients with EGFR mutant in non-small cell lung cancer (NSCLC). At the same time programmed death receptor 1 (PD-1) and its programmed death receptor ligand 1 (PD-L1) inhibitors therapy as the representative immune checkpoint inhibitors (ICIs) has a significant effect in the treatment of lung cancer. The aim of this study was to investigate the correlation between the expression of PD-1 and PD-L1 in NSCLC and clinicopathologic feature, EGFR gene mutation.
METHODS:
The protein expression of PD-1 and PD-L1 was detected by immunohistochemistry from 127 patients with NSCLC and EGFR gene mutation was detected by quantitative polymerase chain reaction (qPCR) to analyze its relation with clinicopathologic feature. Also, the correlation between protein expression of PD-1 and PD-L1 and EGFR mutation.
RESULTS:
The PD-1 positive expression in NSCLC tumor cells and tumor infiltrating immune cells is 53.5% (68/127), PD-L1 is 57.5% (73/127). The PD-1 and PD-L1 expression significantly higher in well-differentiated and moderately-differentiated carcinoma than poorly differentiated carcinoma, I+II than III+IV in clinical staging (P<0.05). The EGFR mutation rate was 46.5% (59/127), correlate with female, without smoking history, adenocarcinoma and well-differentiated and moderately-differentiated patients respectively higher than male, smoking history, squamous carcinoma and poorly differentiated patients (P<0.05). The protein expression of PD-L1 and PD-1 had the consistency in NSCLC patients (kappa=0.107,5, P=0.487). There was a negative correlation between the EGFR mutation and PD-1 and PD-L1 expression (Φ=-0.209, Φ=-0.221, P<0.05). Follow-up of NSCLC patients, the median total survival in under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, with PD-L1 expression patients respectively higher than over the age of 65, squamous carcinoma, poorly differentiated, without PD-L1 expression patients (P<0.05). The median survival of hypo expression patients of PD-L1 significantly higher than hyper expression patient (P=0.04).
CONCLUSIONS
According to the Chinese Expert Consensus on Standards of PD-L1 immunohistochemistry testing for NSCLC, we tested the PD-L1 expression in NSCLC and then the dominant population of anti-PD-1/PD-L1 treatment was screened out. Patients with EGFR mutation were also detected and EGFR mutation was negatively correlated with the expression of PD-1 and PD-L1 as well. On the basis of PD-L1 expression and EGFR mutation status, it may benefit NSCLC patients from individualized treatment. Meanwhile, patients who were under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, hypo expression of PD-L1 have a relatively good prognosis, to provide reference for the prognosis evaluation of NSCLC.
8.Mechanism research status of daidzein in the prevention and treatment of osteoporosis through estrogen-like effect
Shenghang YE ; Yuwei ZHANG ; Xiaowei MENG ; Lihua CHEN ; Weifeng ZHU ; Yongmei GUAN
China Pharmacy 2023;34(20):2556-2560
Osteoporosis, as a systemic bone disease with high incidence rate and high disability rate, has become a research hotspot in recent years. The daidzein in soybean isoflavones can bind with estrogen receptors, simulating the prevention and treatment of osteoporosis with estrogen-like effect. Its mechanism of action includes promoting osteoblast formation and differentiation by activating the Wnt signaling pathway, increasing bone density, and improving bone tissue health; inhibiting osteoclast differentiation and slowing down bone resorption by reducing receptor activator of nuclear factors κB ligand/ osteoprotegerin ratio, downregulating the expression of macrophage colony-stimulating factor (M-CSF); collaborating antioxidant and immune regulation to achieve the goal of preventing and treating osteoporosis. In addition, different doses of daidzein have different effects on bone density and osteoporosis, which may be related to factors such as study design, sample selection, and individual differences.
9.Effect of electroacupuncture on regional homogeneity of brain function in rats with vascular cognitive impairment
Yanyi DING ; Shenghang ZHANG ; Yulu LIU ; Yan YU ; Minguang YANG ; Shengxiang LIANG ; Weilin LIU ; Jing TAO
Chinese Journal of Rehabilitation Theory and Practice 2022;28(1):55-61
Objective To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain functional activity and working memory of rats with vascular cognitive impairment (VCI). Methods Eighteen Sprague-Dawley rats were included, in which twelve rats were ligated bilateral common carotid arteries and six rats were not ligated (sham group). The modeled rats were randomly divided into model group (n = 6) and electroacupuncture group (n = 6). The electroacupuncture group received electroacupuncture at Baihui and Shenting for four weeks. They were assessed with Y maze and Morris water maze before and after intervention, and scaned with resting-state functional magnetic resonance imaging after intervention to calculate regional homogeneity (ReHo). Results Compared with the sham group, alternation rate of Y maze decreased (P < 0.001), and escape latency of Morris water maze increased (P < 0.05) in the model group and the electroacupuncture group before intervention. Compared with the model group, alternation rate of Y maze increased (P < 0.05), and escape latency of Morris water maze decreased (P < 0.05) after intervention in the electroacupuncture group. Compared with the sham group, ReHo of bilateral hippocampus, olfactory cortex, sensory cortex and auditory cortex, and left striatum decreased in the model group; compared with the model group, ReHo of bilateral prefrontal lobe, hippocampus and olfactory cortex, and left amygdala increased in the electroacupuncture group. Conclusion Electroacupuncture at Baihui and Shenting can improve the memory function of VCI rats, which may be related to the functional activities of prefrontal lobes, hippocampus and amygdala.