1.Nucleic acid aptamer and its research progress in glioma
Zhewen KOU ; Li PENG ; Xingmei ZHANG
Journal of International Oncology 2017;44(1):38-40
Nucleic acid aptamer is an oligonucleotide generated by the systematic evolution of ligands by exponential enrichment (SELEX)process from oligonucleotide library.Nucleic acid aptamer can bind to various targets with high specificity and can recognize or inhibit the biological activity of targeting molecular. Glioma-specific aptamers are developed by either targeting the glioma cells or known biomarkers,which can be coupled with nanoparticles,drugs or molecular probes,and can be applied in the imaging,targeted therapy and drug delivery of glioma.
2.Effects of LPS and PMA on proliferation of human len epithelial cells and expression of epidermal growth factor receptor in human len epithelial cells
Zhewen WANG ; Xiaoru SHI ; Tingyu LI ; Shiping ZHOU ; Hong ZHANG
Journal of Jilin University(Medicine Edition) 2006;0(04):-
Objective To observe the effects of LPS and PMA on proliferation of human len epithelial( HLE )cells and expression of epidermal growth factor receptor(EGFR) in HLE cells.Methods The expressions of EGFR protein of HLE cells from felus,adult lens age-related cataract and cultured HLE cells were detected by immunohistochemical staining.The expression of EGFR mRNA was detected by RT-PCR.The effects of LPS (0.5,1.0,2.0 mg?L-1 ) and PMA(25,50,100 nmol?L-1 )on proliferation of HLE cells were detected by MTT colorimetry method,and the EGFR mRNA expression in HLE cells was determined by RT-PCR. Results The expressions of EGFR protein and mRNA were positive in HLE cells from felus,adult lens age-related cataract and cultured HLE cells.The proliferation rates of HLE cells treated with 0.5,1.0,2.0 mg?L-1 LPS were (3.21?0.42)%,(12.25?1.34)% and (36.67?3.65)%,respectively.The proliferation rate of HLE cells in 2.0 mg?L-1 LPS group was higher than those in 0.5 and 1.0 mg?L-1 LPS groups(F=7.709,P0.05).PMA(25,50,100 nmol?L-1 )could not effect the expression of EGFR mRNA in HLE cells .Conclusion Inflammation stimulant factor such as LPS can promote the proliferation of HLE cells by increasing the expression of EGFR and result in occurrence of posterior capsular opacifition(PCO).
3.Effect of adenylate cyclase antagonists andagonist in acute lung injury induced by lipopolysaccharide
Xuefeng WANG ; Feng CHEN ; Shunde SONG ; Zhewen ZHANG ; Huifang TANG
Chinese Pharmacological Bulletin 2017;33(10):1410-1414
Aim To explore the effect of adenylate cyclase(AC) antagonists SQ22536 and agonist forskolin on acute lung injury induced by lipopolysaccharide.Methods ICR mice were randomly divided into normal saline control group(N group), model group(group L), dexamethasone group(group D),AC antagonists s(group SQ) and AC agonist group(group F).The ALI mouse model was induced by instilling intratracheally with LPS(2 mg·kg-1), and 6 h later, the lung tissue and alveolar lavage fluid(BALF) were harvested, pathological changes in lung were observed, white blood cell and neutrophil, albumin content in BALF and myeloperoxidase(MPO) activity of lung tissue homogenate were determined, and tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β), interleukin 6(IL-6) and cAMP content in lung homogenates were detected by ELISA.Results Compared with normal saline group, a large number of neutrophils infiltrated around the pulmonary vessel and airway 6 h after LPS intratracheal instillation in model group.White blood cells and neutrophils and protein content increased in BALF;MPO activity and cAMP levels increased in lung tissues.In the lung tissue TNF-α and IL-6, IL-1β content increased, compared with model group.Forskolin could improve the pathological changes of lung tissue, reduce the total number of leukocytes, number of neutrophils and protein content in BALF, and reduce MPO activity and TNF-α content in lung tissue, at the same time it increased the cAMP content;SQ22536 had no significant effect when compared with model group.Conclusion AC agonists have protective effects on LPS-induced acute lung injury in mice, and the mechanism may be related to elevating cAMP levels, inhibiting neutrophil adhesion and chemotaxis and reducing inflammatory factor levels.
4.Continuous transversus abdominis plane block versus patient-controlled intravenous analgesia after abdominal surgery: A systematic review and Meta-analysis
Dongming LI ; Yun YANG ; Yufan WANG ; Hao WANG ; Zhewen FENG ; Yingchi YANG ; Lan JIN ; Zhongtao ZHANG
International Journal of Surgery 2021;48(4):226-232,F3
Objective:To compare the safety and efficacy of continuous transversus abdominis plane (CTAP) block and patient-controlled intravenous analgesia (PCIA) in abdominal surgery postoperatively.Methods:PubMed, Embase, Web of Science, CNKI and other English and Chinese databases were searched since their establishment to February 2021 with "continuous/modified, transversus/transverse abdominis plane block, TAP block, patient controlled analgesia, patient-controlled analgesia, patient controlled intravenous analgesia, patient-controlled intravenous analgesia, PCA/PCIA/IV-PCA" as the search keywords. According to the analgesia treatment methods, patients were divided into continuous transversus abdominis plane block group (CTAP group) and patient-controlled intravenous analgesia group (PCIA group). Review Manager 5.4 software was used to conduct a Meta-analysis on outcome indicators such as postoperative nausea and (or) vomiting (PONV), dizziness, pain score and recovery status after abdominal surgery. Risk ratio ( RR) was calculated for counting data, Mean ± SD was calculated for measurement data. Heterogeneity was measured by I2, and related data were analyzed by using either a fixed effects model or a random effects model. Results:(1) The results of literature search: A total of 6 randomized controlled trials, including 2 published in English and 4 published in Chinese were analyzed, involving 479 patients. The results of the Meta-analysis: Compared with PCIA, CTAP block had lower incidence of PONV ( RR=0.22, 95% CI: 0.08-0.62, P<0.01), lower incidence of dizziness ( RR=0.27, 95% CI: 0.09-0.79, P=0.02), lower pain scores on movement at 24 h ( MD=-0.75, 95% CI: -1.42--0.08, P=0.03) and 48 h ( MD=-0.68, 95% CI: -1.05--0.31, P<0.001) postoperatively, and earlier time of first mobilization ( MD=-0.49, 95% CI: -0.69--0.30, P<0.001) and first exhaust ( MD=-10.47, 95% CI: -13.53--7.41, P<0.001), with statistically significant differences. However, there were no statistically significant differences in pain scores at rest at 24 h ( MD=-0.25, 95% CI: -0.57-0.08, P=0.14) and 48 h ( MD=-0.15, 95% CI: -0.39-0.09, P=0.22) postoperatively and postoperative length of hospital stay ( MD=-1.01, 95% CI: -2.28-0.26, P=0.12). Conclusion:CTAP block is a relatively safe and effective analgesic method, and it′s more consistent with the concept of enhanced recovery after surgery (ERAS) and can be recommended as an alternative method of PCIA.
5.Advances of the effects of antibody heterogeneity on the function and metabolism of monoclonal antibody drugs
Chen WANG ; Zhewen ZHANG ; Yingchun LI ; Xiquan ZHANG ; Wei ZHAO
Journal of China Pharmaceutical University 2017;48(5):614-621
Antibody drugs often show "heterogeneity",including the related isomers differing from one another in glycosylation,charge or molecular size.Most of these isomers come from post-translational modifications,such as aggregation,degradation,glycosylation,oxidation,deamidation or disulfide misfolding,of the recombinant protein in the "cell factories".These modifications not only influence the quality,safety and efficacy of the antibodies,but also serve as an important indication of product quality throughout the whole process of antibody production.This paper reviews the relationship between glycoslation,charge and size heterogeneities of monoclonal antibodies and drug efficacy,safety,pharmacokinetics as well as immunogenicity,contributing to a better understanding of the relationship between antibody structure and function.It will provide some support and guidance for the research and development of antibody drugs,especially biosimilars.
6.The image characteristics of spectral-domain optical coherence tomography on retinal tuft
Haidong LI ; Lifeng CHEN ; Jun WANG ; Hengli LIAN ; Zhewen ZHANG
Chinese Journal of Ocular Fundus Diseases 2022;38(11):891-894
Objective:To describe the spectral-domain optical coherence tomography (SD-OCT) features of retinal tuft.Methods:A retrospective clinical study. From May 2019 to April 2020, 22 patients (22 eyes) diagnosed as retinal tuft by clinical fundus examination in Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. There were 9 eyes in 9 males and 13 eyes in 13 females. All patients underwent ultra-widefield laser scanning fundus photography and SD-OCT examination. SD-OCT was performed with a 55° wide-angle lens to observe the morphology, color, size and location of the lesions.Results:Twenty-six retinal tuft lesions were found in 22 eyes, all of which were solitary, gray, thylakoid and protrusion. SD-OCT images showed that all the lesions of retinal tuft showed a local protuberant appearance with moderate and hyperreflectivity, which was higher than the surrounding retina plane. In 22 lesions (84.62%, 22/26), there were one or more irregular hyporeflective cavities between the retinal neuroepithelial layers, and the other 4 lesions (15.38%,4/26) contained no hyporeflective cavities. In addition, 23 cases (88.46%, 23/26) with hyperreflective condensed cortical vitreous attached to the retina at the top of lesions, 8 cases (30.77%, 8/26) with retinal tear, and 6 cases (23.08%, 6/26) with shallow retinal detachment.Conclusions:In SD-OCT, the retinal tufts show moderate and strong local protrusion, which are higher than the surrounding retinal plane. In most of the lesions, there are multiple or single irregular weak reflex cavities, and there are hyperreflective condensed cortical vitreous attached to the retina at the top of lesions. Local retinal tears or shallow retinal detachment are present in some lesions.
7.Gender differences in clinicopathological characteristics and prognosis of rectal cancer patients under 50 years old
Mingwei TIAN ; Yun YANG ; Zhewen FENG ; Xiaozhe GU ; Dongming LI ; Jun LI ; Hongwei YAO ; Zhigang BAI ; Yingchi YANG ; Zhongtao ZHANG
International Journal of Surgery 2022;49(11):739-745,C1
Objective:To explore whether there are gender differences in clinical and pathological characteristics and prognosis of young patients with rectal cancer (under 50 years old), and to analyze the risk factors affecting the prognosis of young patients with rectal cancer.Methods:The medical records of 85 young rectal cancer patients admitted to Beijing Friendship Hospital Affiliated to Capital Medical University from January 2015 to December 2020 were retrospectively collected. According to gender, they were divided into male group ( n=50) and female group ( n=35). The age was (43.67±5.50) years old, ranging from 26 to 50 years old. Primary outcome measures were sex, disease-free survival, and overall survival. Secondary outcomes were family history, body mass index (BMI), clinical stage, anemia, whether the female patient was menopausal, whether the female patient took oral estrogen, the location of the primary lesion, whether neoadjuvant therapy was performed, pathological stage, whether accompanied with vascular nerve invasion, and whether postoperative adjuvant therapy was performed. R4.0.2 software was used for statistical analysis. The measurement data with normal distribution in the collected data were expressed as mean±standard deviation ( ± s), and the comparison between groups was analyzed by t test. Count data were expressed as constituent ratio, and analyzed using the chi-square test or Fisher′s exact test. The survival curve was drawn by Kaplan-Meier method, and the difference in survival rate was tested by Log-rank test. Factors with statistical significance in univariate analysis were included in COX proportional regression model for multivariate analysis to screen independent risk factors affecting overall survival. Results:Compared with male patients, a higher proportion of young female patients with rectal cancer were diagnosed with anemia before surgery (42.9% vs 22.0%, P=0.040). The 1-year, 3-year and 5-year overall survival rates were 94.3%, 80.0% and 68.6% in young female patients, and 98.0%, 90.0% and 90.0% in young male patients, respectively. The median disease-free surival was 31.6 months for women and 34.4 months for men. Multivariate analysis showed that female( HR=3.799, 95% CI: 1.312-11.002, P=0.014)and BMI( HR=0.846, 95% CI: 0.724-0.989, P=0.036)were independent risk factors affecting the prognosis of young patients with rectal cancer. Conclusions:Young female patients have a worse prognosis than male patients. Female and BMI are independent risk factors for the prognosis of young rectal cancer patients, and gender should be the key research object of observation in young rectal cancer patients.
8.Advances of long-acting recombinant protein therapeutics.
Ying WEI ; Zhewen ZHANG ; Yamin LU ; Yanju CHENG
Chinese Journal of Biotechnology 2018;34(3):360-368
Some of the recombinant protein therapeutics with short half-life requires high frequent dose or injection, which results in poor patient compliance. This challenge has prompted the development of long-acting recombinant proteins in recent years. Four strategies and methods, including chemical modification, protein engineering, fusion proteins and protein glycosylation are used to modify protein molecule and finally obtain improved pharmacokinetics (PK) properties. This article reviews the four strategies of half-life extension and presents a detailed list of long-acting therapeutics on US, EU and China markets.
9.Expression characteristics and risk analysis of BRCA1 and BRCA2 gene variants in colorectal cancer
Zhewen FENG ; Mingwei TIAN ; Xiaozhe GU ; Jingyu ZHANG ; Xiaobao YANG ; Yun YANG
International Journal of Surgery 2023;50(4):241-246
Objective:To explore the relationship between the occurrence and development of colorectal cancer and the risk of BRCA1 and BRCA2 gene mutations. Methods:Sixty-one patients with colorectal adenocarcinoma admitted to Beijing Friendship Hospital Affiliated to Capital Medical University from January 2022 to March 2022 were tested by second-generation sequencing. Information such as age of onset, gender, histological grade and TNM stage were collected. According to whether the BRCA1 and BRCA2 gene had systemic mutation, the patients were divided into BRCA1 and BRCA2 gene system mutation group and unmutated group. There were 8 cases in the BRCA1 and BRCA2 gene system mutant group and 53 cases in the non-mutant group. The main outcome measures were the relationship between pathogenic or likely pathogenic germline mutations in colorectal cancer and clinicopathological data of patients, including age of onset, gender, tumor location, TNM stage, histological differentiation, and family history. The secondary outcome was the relationship between BRCA1 and BRCA2 gene system mutations and clinicopathological data. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and comparison between groups was analyzed using the t-test. Measurement data with non-normal distribution were represented as M ( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Measurement data were expressed as the number of cases or percentage (%), and Chi-square test was used for comparison between groups. Results:Among 61 colorectal adenocarcinoma patients, the frequency of pathogenic or potentially pathogenic germ line mutations in colorectal cancer was 13.1% (8/61), and the frequency of BRCA1 and BRCA2 mutations was 3.3% (2/61). The frequency of BRCA1 and BRCA2 mutations was 13.1% (8/61). Women with BRCA1 and BRCA2 mutations (75.0% vs 37.7%, χ2=3.947, P=0.047) and right colon cancer (75.0% vs 26.4%, χ2=7.889, P=0.019) were significantly higher than those without mutation. Conclusions:The frequency of BRCA1 and BRCA2 gene mutation is higher in colorectal cancer patients. BRCA1 and BRCA2 gene mutations are recommended for colorectal cancer patients with a family history of breast or ovarian cancer.
10.Correlation of the duration of preoperative biliary drainage and postoperative complications after pancreaticoduodenectomy
Huajun LIN ; Zhewen FENG ; Chengjian GUAN ; Xiaodong ZHANG ; Chenglin XIN ; Xiaozhe GU ; Yiyang MIN ; Dong WANG ; Wei GUO
Cancer Research and Clinic 2023;35(5):321-327
Objective:To investigate the effect of the duration of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy.Methods:The clinical data of 102 patients with benign and malignant hepatopancreatic ductal periampullary tumors who underwent pancreaticoduodenectomy and preoperative biliary drainage in Beijing Friendship Hospital, Capital Medical University from January 2016 to July 2020 were retrospectively analyzed. According to the median duration of preoperative biliary drainage, the patients were divided into short-term drainage group (≤ the median duration of biliary drainage) and long-term drainage group (> the median duration of biliary drainage). The general data, the effect of biliary drainage, inflammation-related indicators and postoperative complications were compared between the two groups. Multivariate logistic regression was used to screen the risk factors related to the postoperative severe complications.Results:Of the 102 patients, 68 (66.7%) were males and 34 (33.3%) were females, with a median age of 63 years (43-80 years). The median duration of preoperative biliary drainage was 14 d. There were 68 patients in short-term drainage group and 34 patients in long-term drainage group. There were no statistically significant differences in age, gender, body mass index (BMI), hypertension, diabetes mellitus, surgery history of upper abdominal, American Society of Anesthesiologists (ASA) grade, carcinoembryonic antigen, carbohydrate antigen 125, alpha-fetoprotein, prothrombin time, pancreaticojejunostomy method, operation time, and pathological type between the two groups (all P > 0.05). However, patients in long-term drainage group had higher conversion rate, more blood loss and longer hospital stay compared with those in short-term drainage group (all P < 0.05). Before biliary drainage, alanine aminotransferase (ALT) level in short-term drainage group was higher than that in long-term drainage group ( Z = -2.59, P = 0.009), and there were no statistically significant differences in aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TB) and direct bilirubin (DB) levels between the two groups before biliary drainage (all P > 0.05). After biliary drainage, DB in short-term drainage group was higher than that in long-term drainage group ( Z = -3.34, P = 0.001), and there was no statistically significant difference in ALT, AST, ALB, TB levels between the two groups (all P > 0.05). There were no statistically significant differences in the levels of white blood cells, neutrophils, lymphocytes and the ratio of neutrophils to lymphocytes between the two groups on the 1st and 3rd day after the operation (all P > 0.05). The total incidence of postoperative related complications in short-term drainage group and long-term drainage group was 63.2% (43/68), 70.6% (24/34), respectively, and the difference was statistically significant ( χ2 = 0.54, P = 0.461); the incidences of bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying, all grades of pancreatic leakage, grade B and C pancreatic leakage were not statistically different between the two groups (all P > 0.05); the incidence of severe postoperative related complications in short-term drainage group was higher than that in long-term drainage group [27.9% (19/68) vs. 8.8% (3/34), χ2 = 4.90, P = 0.027]. Multivariate logistic regression analysis showed that the long-term preoperative biliary drainage was an independent protective factor for postoperative severe complications (long-term drainage vs. short-term drainage: OR = 0.253, 95% CI 0.066-0.975, P = 0.046), while BMI ( OR = 1.174, 95% CI 0.986-1.398, P = 0.071) and pathological type (benign or borderline vs. malignant tumor: OR = 0.247, 95% CI 0.043-1.419, P = 0.117) were not independent influencing factors for postoperative severe complications. Conclusions:Short-term biliary drainage (≤14 d) is a risk factor for postoperative severe complications in patients with hepatopancreatic ductal periampullary tumor undergoing preoperative biliary drainage. Preoperative biliary drainage time is not associated with postoperative total complications, pancreatic leakage, bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying.