1.RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis.
Wen ZHANG ; Yulin PENG ; Meirong ZHOU ; Lei QIAN ; Yilin CHE ; Junlin CHEN ; Wenhao ZHANG ; Chengjian HE ; Minghang QI ; Xiaohong SHU ; Manman TIAN ; Xiangge TIAN ; Yan TIAN ; Sa DENG ; Yan WANG ; Xiaokui HUO ; Zhenlong YU ; Xiaochi MA
Acta Pharmaceutica Sinica B 2025;15(6):3059-3072
Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.
2.Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer.
Meirong ZHOU ; Jiayue WANG ; Yulin PENG ; Xiangge TIAN ; Wen ZHANG ; Junlin CHEN ; Yue WANG ; Yu WANG ; Youjian YANG ; Yongwei ZHANG ; Xiaokui HUO ; Yuzhuo WU ; Zhenlong YU ; Tian XIE ; Xiaochi MA
Journal of Pharmaceutical Analysis 2025;15(3):101118-101118
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
3.MAPK4 Accelerates Progression of Cervical Squamous Cell Carcinoma by Positively Regulating SLC3A2 Expression
Jing YU ; Lu DENG ; Yuting ZHAO ; Zhenlong YUAN ; Lingying WU
Cancer Research on Prevention and Treatment 2024;51(10):803-812
Objective To explore the role of MAPK4 in cervical squamous cell carcinoma(CSCC)for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets.Methods The TCGA cohort was subjected to Kaplan-Meier survival analysis.Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis.A nomogram was constructed based on MAPK4 mRNA levels.Western blot,CCK-8,colony formation,and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC.DIA proteome sequencing was used to identify effector molecules regulated by MAPK4.Combined with the above cell function experiments,the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression.Results CSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis.The constructed nomogram based on MAPK4 can accurately predict the 1-,3-,and 5-year survival rates of patients.Compared with that in normal cervical tissues,MAPK4 protein expre-ssion was up-regulated in tumors.MAP-K4 knockdown substantially inhibited the proliferation,colony formation,mig-ration,and invasion of CSCC ME180 and SiHa cells.SLC3A2 is a downs-tream effector molecule of MAPK4.Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation,colony formation,migration,and invasion.Conclusion MAPK4 is a candidate prognostic biomarker for patients with CSCC.MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression,making it a potential molecular therapeutic target for patients with CSCC.
4.Lymph node dissection for patients with intrahepatic cholangiocarcinoma in China: a meta-analysis
Kangde LI ; Qi CAI ; Weihong LIN ; Junxing YANG ; Yong YU ; Zhenlong WANG ; Guanjing PENG ; Dexiong CHEN ; Chunhong QIN ; Tao HE ; Xiaofeng LUO ; Qianyi LIN
Chinese Journal of Hepatobiliary Surgery 2023;29(4):292-298
Objective:To systematically review the profile of lymph node dissection (LND) for patients with intrahepatic cholangiocarcinoma (ICC) in China.Methods:Using the key words "intrahepatic cholangiocarcinoma" "intrahepatic cholangiocellular carcinoma" "lymph node dissection" "lymphadenec-tomy" "lymph node metastasis", the databases including China Zhiwang, Wanfang, Weipu, Sinomed, PubMed, Embase, Web of Science, Scopus, Cochrane Library were systematically searched. Cohort studies or randomized controlled clinical trials with intraoperative LND documentation and with analysis on the clinicopathologic characteristics or prognostic influences on patients with ICC were included into this meta-analysis from the date of database creation to April 20, 2022. The risk of bias in non-randomized controlled trials was evaluated using the Newcastle-Ottawa scale. A meta-analysis of preoperative imaging lymph node enlargement rates, LND rates, and pathological lymph node metastasis rates were performed using R software.Results:Thirty-three relevant studies that met the systematic evaluation criteria were included, all of which were retrospective cohort studies. All these publications were of medium to high quality. Patients’ enrollment ranged from 1993 to 2020. Patients were enrolled from 20 provinces/autonomous regions/municipalities with a total of 39 medical centers and 4 278 patients. The meta-analysis indicated that the LND rate, preoperative imaging lymph node enlargement rate, pathological lymph node metastasis rate were 47.8%(95% CI: 41.3%-54.3%), 18.5%(95% CI: 7.5%-29.6%) and 51.2%(95% CI: 43.8%-58.6%), respectively. Subgroup analysis showed the LND rate was 36.0%(95% CI: 27.0%-45.0%) in studies with a median year of enrollment before 2010, 48.3% (95% CI: 38.1%-58.6%) in studies from 2010 to 2017, and 53.3%(95% CI: 43.3%-63.2%) in studies after 2017. The LND rates were statistically different in the studies in the different periods of patient enrollment ( P=0.032). Conclusion:The meta-analysis indicated that the overall LND rate for ICC in China was not high but showed an increasing tendency.
5.Application of endoscopic papillary balloon dilatation in the treatment of patients with non-dilated small choledocholithiasis
Zhenlong WANG ; Yusheng ZHANG ; Junxing YANG ; Boyi CHEN ; Yunjing DAI ; Xiaofeng LUO ; Guo-Rong DENG ; Yong YU
Chinese Journal of Hepatobiliary Surgery 2023;29(12):906-910
Objective:To study the efficacy of endoscopic papillary balloon dilatation (EPBD) in the treatment of non-dilated small choledocholithiasis.Methods:Clinical data of 142 patients with non-dilated small choledocholithiasis admitted to Zhanjiang Central People's Hospital from April 2021 to March 2023 were retrospectively analyzed, including 63 males and 79 females, aged (55.1±15.4) years old. Patients were divided into the EPBD group ( n=63) and endoscopic sphincterotomy (EST) group ( n=79). Blood amylase, liver enzymology, liver metabolism, and blood routine were monitored before and 48 hours after treatment. The occurrences of intraoperative bleeding, perforation, post-ERCP pancreatitis (PEP), and cholangitis were compared between the groups. Patients were followed up and screened for stone recurrence by outpatient review 3 to 12 months from discharge. Results:Compared to preoperative data, the white blood cell count, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bili-rubin, and direct bilirubin decreased 48 hours after treatment (all P<0.05). The operation time in EPBD group was slightly longer than that in EST group [(43.1±5.9) min vs. (38.5±4.5) min, P=0.064] without statistical significance. There were no case of perforation in both groups. The incidences of intraopera-tive bleeding [3.17%(2/63) vs. 6.33%(5/79)], PEP [17.46%(11/63) vs. 10.53%(8/79)], and postoperative cholangitis [4.76%(3/63) vs. 1.27%(1/79)] were comparable between the groups (all P>0.05). Conclusion:EPBD could be feasible for non-dilated small choledocholithiasis, which does not increase the operation time and incidence of adverse events compared to EST.
6.Arthroscopic Bristow procedure using suture-button fixation for treatment of recurrent anterior shoulder instability
Zhenlong BAI ; Zhekun ZHOU ; Guangcheng ZHANG ; Qingxiang HU ; Yanfeng HUANG ; Bangjun CHENG ; Xiaofeng ZHANG ; Daoyun CHEN ; Weilin YU ; Yaohua HE
Chinese Journal of Trauma 2021;37(7):641-645
Objective:To investigate the clinical outcome of arthroscopic suture-button Bristow procedure using suture-button fixation for treatment of recurrent anterior shoulder instability.Methods:A retrospective case series study was conducted to analyze 28 patients with recurrent anterior shoulder instability admitted to Shanghai Sixth People’s Hospital from March 2015 to September 2018,including 26 males and 2 females,aged 18-36 years [(24.1 ± 3.2)years]. Preoperative MRI showed Bankart injury and three-dimensional CT showed glenoid bone defect > 15%. The Hill-Sachs injury was found in 27 patients. Arthroscopic Bristow procedure was used to fix coracoid process graft with the suture-button plate and glenoid labial complex was repaired with the suture anchor to treat anterior instability of the shoulder joint. The visual analogue scale (VAS),American shoulder and elbow surgeon (ASES) scale,Constant score and Rowe score were used to evaluate the shoulder joint function preoperatively,at postoperative 3,6,12 months and at the last follow-up. The postoperative infection,neurovascular injury,redislocation and other complications were recorded,and the incidence rate was calculated. The bone resorption and bone healing of coracoid process graft were analyzed by CT.Results:All patients were followed up for 22 - 36 months [(24.5 ± 6.3) months]. Three months after operation,the VAS,ASES scale and Constant score were not significantly different from those before operation ( P > 0.05). In comparison,the Rowe score was significantly higher than that before operation ( P < 0.05). Six and twelve months after operation,the VAS,ASES scale,Constant score and Rowe score were significantly improved from those before operation ( P < 0.05). At the last follow-up,the VAS decreased from (2.7 ± 1.5)points preoperatively to (0.8 ± 0.3)points,the ASES scale increased from (78.6 ± 12.7)points preoperatively to (92.4 ± 8.4)points,the Constant score increased from (43.4 ± 5.2) points preoperatively to (81.6 ± 6.7) points,the Rowe score increased from (52.3 ± 7.1)preoperatively to (92.7 ± 5.4) points ( P < 0.05). During the follow-up,there was no infection,neurovascular injury,re-dislocation and other complications. In addition,24 (86%) out of the 28 patient showed healing of coracoid process grafts,and the overall bone resorption rate was (18.4 ± 6.1)%. No patients had glenohumeral joint osteoarthritis. Conclusion:Arthroscopic Bristow procedure using suture-button fixation for treatment of recurrent anterior shoulder instability has advantages of a low rate of postoperative complications and a high union rate,indicating an effective and safe surgical procedure.
7. Influencing factors for reproductive health of female workers in petrochemical industry
Zhenxia KOU ; Shulin WANG ; Zhenlong CHEN ; Yuhong HE ; Wenlan YU ; Liangying MEI ; Hendong ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(2):139-143
Objective:
To investigate the reproductive health status of female workers in petrochemical industry, and to provide a reference for improving reproductive health status and developing preventive and control measures for female workers in petrochemical industry.
Methods:
A face-to-face questionnaire survey was performed from January to October, 2016. The Questionnaire on Women's Reproductive Health was used to investigate the reproductive health of female workers in petrochemical industry. The multivariate logistic regression model was used to identify the influencing factors for reproductive health of female workers in petrochemical industry.
Results:
Among the 7485 female workers, 1 268 (40.9%) had abnormal menstrual period, 1 437 (46.4%) had abnormal menstrual volume, 177 (28.5%) had hyperplasia of mammary glands, and 1 807 (24.6%) had gynecological inflammation. The reproductive system diseases in female workers in petrochemical industry were associated with the factors including age, marital status, education level, unhealthy living habits, abortion, overtime work, work shift, workload, video operation, occupational exposure, positive events, and negative events, and among these factors, negative events (odds ratio[
8.Synthesis of Boronic Acid-functionalized Soluble Dendrimers and Its Application in Detection of Human Liver Microsomal Glycoprotein Based on Enzyme-linked Immunosorbent Assay
Tiantian LI ; Liyuan ZHANG ; Zhenlong YU ; Xiaochi MA ; Sa DENG
Chinese Journal of Analytical Chemistry 2017;45(9):1259-1263
The glycoproteins in the biological sample are low abundance and are susceptible to be inhibited and interfered by other non-glycoproteins.An enrichment step is usually required before the glycoprotein analysis, but the operation steps of conventional solid-phase-based glycoprotein enrichment methods are difficult to be compatible with the most classical enzyme-linked immune sorbent assay (ELISA) technique.In this study, a novel water-soluble dendrimer based boronic acid capture (DBC) material was developed using PAMAM 4.0 as the carrier and boronic acid as the affinity group.The method was applied to the detection of glycoproteins in human liver microsomes using ELISA.In this study, the DBC enrichment conditions were optimized by model glycoprotein, and then its sensitivity and anti-interference ability were investigated.This method was applied to the enrichment of glycoproteinsin human liver microsomal.The results showed that the enrichment selectivity of DBC for glycoprotein could be up to 100000 folds, and the enrichment signal of glycoprotein could be increased by 100 times.Therefore, the ELISA method using DBC as a novel enrichment material for glycoprotein had high sensitivity and selectivity in detection of biological samples with only one simple incubation step, which was useful for glycoproteins researches.
9.Significance of the MELD scoring system in surgical treatment of obstructive jaundice
Zhenlong WANG ; Yong YU ; Boyi CHEN ; Chencai LI ; Rong LI
Chinese Journal of Hepatobiliary Surgery 2014;20(7):503-506
Objective To prospectively study the clinical significance of the MELD scoring system in surgical treatment of obstructive jaundice.Methods 112 patients with obstructive jaundice who were admitted into our hospital from January 2009 to December 2013 were divided into two groups:group A (Stage Ⅰ PTCD and stage Ⅱ open operation,n =53) and group B (1 stage open surgery,n =59).The amount of intraoperative bleeding blood loss,operation time,postoperative complications,duration of hospitalization,mortality rate,and the changes in liver function after surgery were compared between the two groups.Results The differences in the liver function index of the two groups on the same postoperative date were significantly different (P < 0.05).The liver function of group A recovered faster than group B.Patients in group A with a MELD < 10 points stayed in hospital significantly longer when compared with patients in group B.For patients in group A with MELD > 10 points,the operation time,bleeding volume,postoperative complications and hospitalization were significantly less than the patients in group B (P < 0.05).There were 3 patients (group B) who died with MELD ≥ 20 points after operation.Conclusions In patients with obstructive jaundice with a MELD score greater than 10 points,especially those with a score equal to or greater than 20,PTCD should be performed first to relieve biliary tract obstruction,followed by a stage Ⅱ open surgical operation after the liver function had improved.MELD had important clinical significance in the evaluation of operation risk in patients with obstructive jaundice.
10.Establishment and drug susceptibility test of isoniazid resistant Mycobacterium smegmatis.
Pingping JIA ; Lili ZHAO ; Xiaoyu LI ; Quan ZHANG ; Zhenlong LIU ; Xin WANG ; Liyan YU ; Lixun ZHAO ; Shan CEN
Acta Pharmaceutica Sinica 2011;46(4):377-82
With the emergence of drug resistant tuberculosis, it is very urgent to find novel anti-tuberculosis drugs, especially novel anti-drug-resistant tuberculosis drugs. Because of the slow growth and the need to work in a biosafty environment of Mycobacterium tuberculosis, the development of evaluation of drug effect is severely impeded. In order to solve these issues, non-pathogenic fast-growing Mycobacterium smegmatis is introduced as test organism. The inhA is one of a target of isoniazid (INH) overexpression or mutation of this gene in Mycobacterium tuberculosis conferring resistant to INH. A recombinant plasmid bearing inhA was constructed and electroporated into Mycobacterium smegmatis, using shuttle expression vector pMV261. Transformants were induced to express a protein of inhA, identified by SDS-PAGE. Results show that Mycobacterium smegmatis containing inhA plasmids exhibited 100-fold or greater increased resistance to INH, but it conferred no increased resistance to others first-line anti-tuberculosis drugs. Resazurin microtiter assay plate testing of Mycobacterium smegmatis susceptibility to drugs is a rapid, simple, and inexpensive method and could decrease color background of drugs by detecting fluorescence. It will be benefit for high-throughout screening of drugs of anti-isoniazid-resistant Mycobacteria.

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