Inhibitory effect of royal jelly acid on proliferation of human colon cancer SW620 cells and its network pharmacological analysis / 吉林大学学报(医学版)

Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Clinical application of magnetic resonance imaging-guided radiation therapy in the treatment of pancreatic cancer / 中华放射肿瘤学杂志

At present, pancreatic cancer is a solid tumor with the worst prognosis. Compared with surgery and chemotherapy, radiotherapy plays an auxiliary role in the treatment of pancreatic cancer. In recent years, significant advances have been achieved in radiotherapy technology, which have been gradually applied in the diagnosis and treatment of pancreatic cancer. In this article, the progress in radiation therapy in the treatment of pancreatic cancer was reviewed, especially the clinical application of magnetic resonance imaging-guided radiation therapy in the treatment of pancreatic cancer, aiming to deepen the understand of the progress in radiation therapy for pancreatic cancer, and providing reference for improving the survival rate of pancreatic cancer patients.

Inhibitory Effect of Sesquiterpenoid M36 from Myrrha on Growth of Human Hepatoma Cells / 中国实验方剂学杂志

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC50） value of M36 for 48 h was 5.03 μmol·L-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Expression of CDKN1B in colorectal cancer and its relationship with clinicopathological features / 肿瘤研究与临床

Objective:To explore the relationship between CDKN1B expression and clinicopathological features in colorectal cancer.Methods:Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA) database were used to analyze the expression of CDKN1B in colorectal cancer tissues and its relationship with the prognosis of colorectal cancer. The data of 98 patients with colorectal cancer who underwent surgery from January 2020 to December 2021 at Yixing Clinical College of Yangzhou University Medical School were retrospectively analyzed, and pathological specimens were collected. Immunohistochemistry method was used to detect CDKN1B protein expression level in colorectal cancer and paracancerous normal tissues (2 cm from the tumor site) and the correlation of CDNK1B expression with clinicopathological characteristics was analyzed.Results:The results of bioinfomatics analysis and the prediction from HPA database and GEPIA database suggested that the expression level of CDKN1B in colorectal cancer was lower than that in the normal colorectal tissues; In HPA database, the 5-year overall survival rate of patients in the CDKN1B high expression (425 cases) was higher than that of those in the CDKN1B low expression (172 cases) (65% vs.51%), and the difference in the overall survival of both group was statistically significant ( P < 0.001). GEPIA database staging module analysis showed that CDKN1B gene expression level was correlated with the pathological stage of patients with colorectal cancer ( P = 0.033). Immunohistochemistry analysis showed that CDKN1B expression was localized in the nucleus and cytoplasm. The proportion of patients with CDKN1B high expression in colorectal cancer tissues was lower than that in paracancerous normal tissues [18.37% (18/98) vs. 90.82% (89/98), P < 0.01]. The proportion of CDKN1B high expression in cancer tissues of colorectal cancer patients with poor differentiation [poor differentiation vs. high-middle differentiation: 3.70% (1/27) vs. 23.94% (17/71)], lymph node metastasis [metastasis vs. non-metastasis: 6.38% (3/53) vs. 29.41% (15/45)], TNM higher stage [stage Ⅳ vs. Ⅲ vs. Ⅱ vs. Ⅰ: 5.00% (1/20) vs. 13.95% (3/33) vs. 20.59% (8/30) vs. 36.36% (6/15)] was lower (all P < 0.05), while there were no statistically significant differences in the proportion of patients with CDKMB high expression in colorectal cancer tissues among different subgroups stratified by gender, age and tumor size (all P > 0.05). Conclusions:CDKN1B is mainly expressed in the nucleus and cytoplasm, and is lowly expressed in colorectal cancer. The lower CDKN1B expression may indicate the poorer prognosis of patients. CDKN1B can be used as a marker for clinical diagnosis, treatment and prognosis evaluation of colorectal cancer.

Risk factors for acute kidney injury after off-pump coronary artery bypass grafting: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To analyze the risk factors for acute kidney injury (AKI) after off-pump coronary artery bypass grafting (OPCABG). Methods     The PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang data, CBM, VIP, CNKI were searched by computer for researches on risk factors associated with the development of AKI after OPCABG from the inception to March 2022. The meta-analysis was performed using RevMan 5.4 software. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. Results    A total of 18 researches were included, involving 9 risk factors. The NOS score of all included studies was≥6 points. Meta-analysis results showed that age [OR=1.03, 95%CI (1.01, 1.06), P=0.020], body mass index (BMI) [OR=1.10, 95%CI (1.05, 1.15), P<0.001], history of hypertension [OR=1.45, 95%CI (1.27, 1.66), P<0.001], history of diabetes [OR=1.50, 95%CI (1.33, 1.70), P<0.001], preoperative serum creatinine level [OR=2.05, 95%CI (1.27, 3.32), P=0.003], low left ventricular ejection fraction [OR=4.51, 95%CI (1.39, 14.65), P=0.010], preoperative coronary angiography within a short period of time [OR=2.10, 95%CI (1.52, 2.91), P<0.001], perioperative implantation of intra-aortic balloon pump [OR=3.42, 95%CI (2.26, 5.16),  P<0.001], perioperative blood transfusion [OR=2.00, 95%CI (1.51, 2.65), P<0.001] were risk factors for AKI after OPCABG. Conclusion    Age, BMI, history of hypertension, history of diabetes, preoperative serum creatinine level, low left ventricular ejection fraction, preoperative coronary angiography within a short period of time, perioperative implantation of intra-aortic balloon pump, perioperative blood transfusion are risk factors for AKI after OPCABG. Medical staff should focus on monitoring the above risk factors and early identifying, in order to prevent or delay the onset of postoperative AKI and promote early recovery of patients.

Literature analysis of the design and results of the First-In-Human clinical trials of drugs from 2009 to 2020 / 中国临床药理学与治疗学

AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.

miR-575 Promotes the Proliferation and Invasion of Non-small Cell Lung Cancer Cell by Negatively Regulating BLID Expression / 现代生物医学进展

Objective:To explore the mechanisms of regulation of miR-575 on the proliferation and invasion properties of non-small cell lung cancer cell (NSCLC).Methods:Real-time PCR was selected to detect the expression of miR-575 and BLID in differ ent NSCLC cell lines.CCK-8 assay was processed to measure the alternations of A549 cell proliferation at different time points after transfection of miR-575 mimic and miR-575 inhibitor.The invasion ability of A549 cells was evaluated by transwell.The targeting of BLID by miR-575 was predicted by Targetcan software and verified by dual-Luciferase assay.BLID protein expression level was detected by western blot.Results:miR-575 highly expressed in NSCLC cell lines,including A549,SPC-A1,H1299,H1650 (P＜0.001),miR-575 mimic could efficiently elevated the expression ofmiR-575 in A549 cells (P＜0.001),and strengthened the proliferation and invasion ability of NSCLC cells (P＜0.05),while,transfection of miR-575 inhibitor could down-regulate the expression ofmiR-575,and also inhibit the proliferation and invasion ability of NSCLC cells (P＜0.01).Targetscan software predicted that BLID might be the target gene of miR-575,and dual-luciferase assay revealed that miR-575 could obviously decrease the luciferase reaction of wild type BLID 3'UTR (P＜0.01),besides,miR-575 could down-regulate the protein expression ofBLID (P＜0.01).Real-time PCR results showed that NSCLC cell lines had lower level of BLID mRNA expression compared with 16HBE control cells (P＜0.001),and restore of BLID could markedly inhibited cell proliferation and invasion ability (P＜0.05),which could be reversed by miR-575 co-tranfection (P＜0.01).Conclusion:In NSCLC cells,the expression ofmiR-575 could promote cell proliferation and invasion ability by directly regulating downstream target tumor-suppressor gene BLID expression.

Research on Clinical Application of Fufang Kushen Injection in Treating Colonic Malignant Tumor in the Real World / 世界科学技术-中医药现代化

This study was aimed to analyze the clinical application of Fufang Kushen (FFKS) injection in treating colonic malignant tumors in the real world based on the hospital information system (HIS) database,in order to provide references for clinical application of FFKS injection.The electronic medical records were extracted from 3328 patients with colonic malignant tumors using FFKS injection from 22 large-scale triple-A hospitals nationwide based on the data warehouse of HIS established by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences.The descriptive analysis of frequency and rate was made on general characteristics,diagnostic characteristics,dosage and characteristics of medication information,characteristics of drug combination,characteristics of discharge outcome and etc.The results showed that the average age of patients treated with FFKS injection for colonic malignant tumors was 61.85 years old,with more males than females.Patients were mainly hospitalized from the department of digestology and oncology.The single dose of medication was usually 10-20 ml.The main course of treatment was 4-7 days.Common clinical medications in combination included Tropisetron injection,thymus peptide injection,oxaliplatin injection,fluorouracil,leucovorin injection and etc.The total efficiency was 39.78％ based on the discharge outcomes.It was concluded that the population characteristics of using FFKS injection to treat colonic malignant tumors were clear and in line with the general rule of colonic malignant tumors.The clinical dosage and scope of FFKS injection in the real world of colonic malignant tumors treatment basically meet the medication instruction.The clinical drug combination type is more extensive.

Effect of Aortic Arch Type on Technical Indicators in Patients With Carotid Artery Stent Implantation / 中国循环杂志

Objective: To explore the effect of the aortic arch type on technical indicators in patients with carotid artery stent implantation. Methods: We retrospectively analyzed 224 consecutive patients treated in Fu Wai hospital for unilateral carotid artery stent implantation from 2011-01 to 2012-12. We summarized the catheter category, type and the operating techniques including ① retracement, turn and insertion of the catheter, ② retracement, turn of catheter+the guidance of guide wire,③ retracement, turn of catheter+the guidance of guide wire+the supporting of another catheter, ④ using special graphic catheter+the guidance of guide wire+the supporting of another catheter. The procedural X-ray exposure time, dosage of contrast agent and operation related complications were recorded. According to Myla classiifcation, the aortic arches were divided into Myla I, Myla II and Myla III types. Results: There were 7/224 (3.1%) patients with Myla I aortic arch, 113 (50.4%) with Myla II aortic arch and 104 (46.4%) with Myla III aortic arch. A total of 48/104 (46.2%) Myla III patients used special techniques (tech③, tech④), it was more than the patients with Myla I, (1/7,14.3%) and Myla II (17/113, 15.0%), P Myla III was 96.2%, it was lower than those with Myla I (100%) and Myla II (100%), P=0.045. The procedural complication rate in patients with Myla III was 22.1%, it was higher than those with Myla I (0%) and Myla II (8.9%), P=0.007. Conclusion: The aortic arch type is the important inlfuential factor for the techniques used in carotid stent implantation. There were more dififculties and complications for stent implantation in patients with Myla III aortic arch.

Screening and functional analysis of microRNA expression in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang / 中南大学学报(医学版)

OBJECTIVE@#To explore the differential expression of microRNA (miRNA) in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang and to predict the target genes of the miRNAs.
@*METHODS@#Samples of HPV16-positive squamous carcinoma of the cervix from 5 Uygurs were collected for miRNA microarray assay. The differentially expressed miRNAs were selected for further verification by real-time quantitative RT-PCR. The software, including targetscan, miRwalk, miRanda and pictar, were used to predict the target genes of the verified miRNAs.
@*RESULTS@#Eighteen differentially expressed miRNAs were identified by miRNA microarray assay. The significantly differentially expressed miRNA-138 and miRNA-720 were verified by real-time quantitative RT-PCR. According to the prediction, the target genes for miRNA-138 were EZH2, LYPLA1, ARHGEF3, CLNS1A, EIF4EBP1, GNAI2, LIMK1, RHOC, ROCK2, SLC20A1, TERT, and H2AFX, while for miRNA-720 were EZH2, AGAP2, SPOCK2, FGF14, HNRNPA2B1, QKI, FOXG1, ACVR1B, DNMT3A, EPHB2, LATS2, KRAS, CCND2, NBN, ENAM, AMELX, PRNP, and CALB1.
@*CONCLUSION@#miR-138 and miR-720 are the down-regulated target miRNAs in HPV16-positive squamous carcinoma of the cervix in the Uygur of southern Xinjiang. The common target gene for miR-138 and miR-720 is EZH2, which might be related to cervical squamous carcinoma invasion and metastasis.

Investigation of microRNA expression on Uygur cervical squamous cell carcinoma in southern Xinjiang / 中国癌症杂志

Background and purpose:Cervical cancer is one of the most common cancer in Xinjiang, especially for Uygur from southern Xinjiang and its pathogenesis is not clear. MicroRNA (miRNA) is a class of small non-coding RNA playing an important regulatory role. Its expression and dysfunction is closely related to the development of tumors. In this study, we screen and preliminary analyse expression of miRNA in cervical squamous cell carcinoma samples with human papillomavirus (HPV) 16 positive of Uygur patients. The target genes of miRNA were predicted.Methods:miRNAs were pre-screened by using miRNA microarray technology in 5 cases of HPV16 positivity Uygur patients from southern Xinjiang with cervical squamous cell carcinoma. Fifteen cases specimens were examined by qRT-PCR for preliminary veriifcation, and 83 cases of cervical cancer were detected and analysed the expression of miRNA; Targeted genes were predicted by using four softwares of target scan, miRwalk, miRanda and Pictar.Results:Eighteen differentially expressed miRNAs were selected by SAM software in 5 cases of HPV16 positivity southern Xinjiang Uygur cases with cervical squamous cell carcinoma.miRNA-138 and miRNA-720 were found expressed signiifcantly different by initial veriifcation. Contrasted with 40 normal cases, miR-138 and miR-720 were down-regulated in 83 Uygur patients from southern Xinjiang with cervical squamous cell carcinoma (P0.05). miRNA-720 was correlated with clinical stage and tumor size (P<0.05); And the commonly targeted gene between miRNA-138 and miRNA-720 was EZH2.Conclusion:miRNA-138 and miRNA-720 were downregulated in Uygur patients from southern Xinjiang with cervical squamous cell carcinoma, and the common target gene was EZH2.The expression of miR-720 and miR-138 were correlated with relevant risk factors of invasion and metastasis.

Automated Urine Analyzer for Screening Hospital Urinary Tract Infection and Its Value / 中华医院感染学杂志

OBJECTIVE To investigate the value of screening hospital urinary tract infection with UF-100 automated urine analyzer. METHODS It was to count the bacteria and white blood cells in 422 urine specimens with UF-100 as well as to culture the specimens quantitatively.Then the sensitivity and specificity of UF-100 counts and the correspondence of the two methods were evaluated with Yerushalmy mode. RESULTS Compared with the culture results,UF-100 showed a sensitivity of 81.5%,specificity of 63.9%,positive predictive value of 29.1%,negative predictive value of 95.0%,false positive rate of 30.5%,false negative rate of 2.8% and an accuracy of 67.2%. CONCLUSIONS The UF-100 is excellent in analyzing urine specimens,and its bacteria counts can be a valuable indicator in screening hospital urinary tract infection.

Antibiotics Use During Perioperative Period:An Intervention Study / 中华医院感染学杂志

OBJECTIVE To explore clinic effect of antibiotics intervention during perioperative period guided by rational usage of antibiotics.METHODS Selected all the discharged patients of Oct 2003 and Apr 2004 as group without intervention and that of Oct 2004,Apr and Oct 2005,and Apr and Oct 2006 as group with intervention,to analyze their antibiotics usage data.RESULTS After continuous intervention,antibiotics utilization ratio promoted,especially the antibiotics half an hour pre-operation utilization ratio of clean-contaminated incision and contaminated incision improved from 48.9% and 14.3% in pre-intervention group to 88.2% and 50.0% in post-intervention group,respectively,antibiotics cost to total drug fee ratio decreased from 30.51% to 24.06%.CONCLUSIONS Effective and feasible intervention can promote antibiotics prophylaxis utilization during perioperative period and decrease incision infection and medical expense.