Objective To investigate the impacts of forkhead box M1(FOXM1)on the proliferation,invasion,and drug resistance of gastric cancer cells by regulating the circular RNA circ_NOTCH1.Methods Western blotting and real-time quantitative PCR were performed to determine the expression of FOXM1 protein and circ_NOTCH1,respectively,in the gastric cancer tissue,para-carcinoma tissue,human normal gastric mucosa epithelial cell line GES-1 and gastric cancer cell lines MGC-803,HGC-27,and BGC-823.BGC-823 cells were classified into the following groups:control,short hairpin RNA FOXM1(sh-FOXM1)and negative control(sh-NC),small interfering RNA circ_NOTCH1(si-circ_NOTCH1)and negative control(si-NC),and sh-FOXM1+circ_NOTCH1 overexpression plasmid(sh-FOXM1+pcDNA-circ_NOTCH1)and sh-FOXM1+negative control(sh-FOXM1+pcDNA).CCK-8 assay and clone formation assay were employed to measure the cell proliferation,and Transwell assay to measure cell invasion.After treatment with 1.0 mg/L adriamycin for 48 h,the cell resistance in each group was analyzed.Western blotting was employed to determine the expression levels of FOXM1,proliferating cell nuclear antigen(PCNA),Bax,multi-drug resistance-associated protein 1(MRP1),and multi-drug resistance gene 1(MDR1).RNA pull-down and RNA immunoprecipitation were employed to examine the binding of circ_NOTCH1 to FOXM1 protein.Results Compared with those in the para-carcinoma tissue,the expression levels of FOXM1 protein and circ_NOTCH1 in the gastric cancer tissue were up-regulated(all P<0.001).Compared with GES-1 cells,MGC-803,HGC-27,and BGC-823 cells showed up-regulated expression levels of FOXM1 protein and circ_NOTCH1(all P<0.001).Compared with the control group and sh-NC group,the sh-FOXM1 group with down-regulated expression of FOXM1 protein and circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with the control group and the si-NC group,the si-circ_NOTCH1 group with down-regulated expression of circ_NOTCH1 showed decreased optical density value,clone formation rate,cell invasion number,and cell viability,down-regulated expression of PCNA,MRP1,and MDR1,and up-regulated expression of Bax protein in BGC-823 cells(all P<0.001).Compared with sh-FOXM1 group and sh-FOXM1+pcDNA group,the sh-FOXM1+pcDNA-circ_NOTCH1 group with up-regulated expression of circ_NOTCH1 showed increased optical density value,clone formation rate,cell invasion number,and cell viability,up-regulated expression of PCNA,MRP1,and MDR1,and down-regulated expression of Bax protein(all P<0.001).FOXM1 protein was able to interact with circ_NOTCH1.Conclusion Interference with FOXM1 may inhibit the proliferation,invasion,and drug resistance of gastric cancer cells by silencing circ_NOTCH1 expression.
Humans ; bcl-2-Associated X Protein/metabolism* ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Drug Resistance ; Forkhead Box Protein M1/metabolism* ; Gene Expression Regulation, Neoplastic ; MicroRNAs/genetics* ; Proliferating Cell Nuclear Antigen/metabolism* ; Receptor, Notch1/metabolism* ; RNA, Small Interfering/genetics* ; Stomach Neoplasms/genetics*

OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells. METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR. RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue ( CONCLUSIONS The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.
Breast Neoplasms/genetics* ; Carcinoma, Ductal, Breast/genetics* ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A

Child ; Eosinophilia ; diagnosis ; drug therapy ; Gastroenteritis ; classification ; diagnosis ; drug therapy ; Humans ; Male

Dipeptides ; administration & dosage ; therapeutic use ; End Stage Liver Disease ; drug therapy ; virology ; Female ; Hepatitis B virus ; Humans ; Male

AIM: To investigate the relationship between platelet parameters and macular edema(ME)in retinal vein occlusion(RVO)patients with different OCT types.

METHODS: Retrospective study. A total of 126 eyes in 126 patients with RVO were enrolled in the ophthalmology department of the Fifth Affiliated Hospital of Zhengzhou University from December 2016 to February 2021, among whom, 51 eyes with central retinal vein occlusion(CRVO)were included, branch retinal vein occlusion(BRVO)included 75 eyes, 31 eyes without ME(non-ME)and 95 eyes with ME. According to the morphology of OCT, ME was divided into 26 eyes of diffuse retinal thickening(DRT), 30 eyes of cystoid macular edema(CME)and 39 eyes of serous retinal detachment(SRD), the platelet parameters of patients with different groups including platelet count(PLT), mean platelet volume(MPV), plateletcrit(PCT)and platelet distribution width(PDW)were collected and statistical analysis were performed.

RESULTS:The MPV value and CMT value of ME group was higher than that of Non-ME group(all P<0.001), the MPV value of SRD group was higher than that of DRT group and CME group(all P<0.001), but there was no statistically significant difference in MPV between DRT group and CME group(P=0.526), CMT in SRD group was significantly higher than that in DRT group and CME group(P<0.001), and there was no significant difference in CMT between DRT group and CME group(P=0.190).

CONCLUSION:MPV has differences in patients with RVO ME with different OCT classifications, activated platelets may be closely related to the occurrence and development of SRD.

OBJECTIVE: To explore the clinical efficacy of posterior percutaneous endoscopic discectomy(PPECD) in the treatment of cervical spondylotic radiculopathy. METHODS: A total of 56 patiens with single segment cervical spondylotic radiculopathy from December 2017 to October 2020, were randomly divided into observation group and control group. In observation group, there were 16 males and 11 females, including 8 cases of C_4,5, 13 cases of C_5,6 and 6 cases of C_6,7 performed posterior percutaneous endoscopic discectomy, aged from 34 to 61 years old with an average of (51.15±6.29) years old. In control group, there were 19 males and 10 females with single segment cervical spondylotic radiculopathy including 10 cases of C_4,5, 14 cases of C_5,6 and 5 cases of C_6,7 performed anterior cervical discectomy and fusion, aged from 40 to 65 years old with an average of (53.24±5.31) years old. The operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were recorded. Visual analogue scale(VAS) and neck disability index(NDI) were used to evaluate the clinical efficacy. Cervical plain films or MRIs, CTs were taken for re-visiting patients. RESULTS: All patients were followed up more than 2 years. The observation group patients were followed up, the duration ranged from 24 to 42 months with an average of (30.48±4.91) months. The control group patients were followed up, the duration ranged from 25 to 47 months, with an average of (32.76±4.53) months. Compared with control group, operative time, intraoperative blood loss, postoperative time of lying in bed and length of postoperative hospital stay were decreased(P<0.05). Compared with pre-operation, VAS of neck and upper limb and NDI at the latest follow-up between two groups were significantly improved(P<0.05). Compared with control group, VAS of neck and upper limb at 1 day after operation in observation group were significantly reduced(P<0.05). There was no significant difference in VAS of neck and upper limb and NID at 1, 3 months and the latest follow-up after operation between two groups(P>0.05). In the observation group, one patient's deltoid muscle strength was weakened to grade 4 after operation, and returned to normal after 12 weeks of conservative treatment. In control group, there was 1 case of postoperative adjacent spondylosis with symptoms of spinal compression after 2 years operation, then underwent cervical artificial intervertebral disc replacement. And there was 1 case of dysphagia after operation in control group and improved after 1 year. There was no significant difference in incidence of complications between two groups. CONCLUSION PPECD has advantages of shortening operative time, decreasing intraoperative blood loss, reducing postoperative time of lying in bed and length of postoperative hospital stay. However, applicable age range of patients and long-term clinical efficacy needs further study.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Radiculopathy/surgery* ; Cervical Vertebrae/surgery* ; Treatment Outcome ; Diskectomy ; Spondylosis/surgery* ; Blood Loss, Surgical ; Postoperative Hemorrhage ; Retrospective Studies ; Spinal Fusion

ObjectiveTo investigate the value of combined determination of Model for End-Stage Liver Disease （MELD） score， albumin-bilirubin （ALBI） score， and β2-microglobulin in the diagnosis of liver cirrhosis with acute kidney injury （AKI）. MethodsClinical data were collected from 258 patients with liver cirrhosis who attended The First Affiliated Hospital of Zhengzhou University from October 2019 to October 2022， and according to the presence or absence of AKI， they were divided into AKI group with 117 patients and non-AKI group with 141 patients. The changes in each index were compared between the two groups and between the patients with different stages of kidney injury. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the efficacy of each index in the diagnosis of liver cirrhosis with AKI. ResultsCompared with the non-AKI group， the AKI group had significantly higher age （t=2.307， P=0.022）， proportion of patients with hepatic encephalopathy （χ²=18.064， P<0.001） or with spontaneous peritonitis （χ²=16.397， P<0.001）， mortality rate （χ²=45.251， P<0.001）， levels of creatinine （Z=-8.737， P<0.001） and β2-microglobulin （Z=-8.829， P<0.001）， and scores of CTP （Z=-4.058， P<0.001）， ALBI （t=2.563， P=0.011）， and MELD （Z=-5.628， P<0.001）， as well as a significantly shorter length of hospital stay （Z=-3.391， P=0.001）. There were significant differences in creatinine， β2-microglobulin， MELD score， and ALBI score between the patients with stage 1， 2 or 3 AKI （P<0.05）， while there was no significant difference in CTP score between these three groups （P>0.05）. The combined determination of ALBI score， MELD score， and β2-microglobulin had an area under the ROC curve （AUC） of 0.837 （95% confidence interval ［CI］： 0.782 — 0.892）， with a sensitivity of 75.2% and a specificity of 90.8%； ALBI score combined with MELD score had an AUC of 0.700 （95%CI： 0.636 — 0.764）， ALBI score combined with β2 microglobulin had an AUC of 0.823 （95%CI： 0.765 — 0.881）， and MELD combined with and β2 microglobulin had an AUC of 0.835 （95%CI： 0.779 — 0.890）， suggesting that combined determination of ALBI score， MELD score， and β2-microglobulin had a better diagnostic efficacy than ALBI score， MELD score， or β2-microglobulin used alone or in pairs， as well as a better diagnostic efficacy than creatinine. ConclusionCombined determination of ALBI score， MELD score， and β2-microglobulin has a relatively high value in the diagnosis of liver cirrhosis with AKI.

OBJECTIVE: To obtain the microcrystal agents of sorafenib and examine the in vivo anti-tumor efficiency of sorafenib-microcrystal on hepatocellular carcinoma cells. METHODS: The solubilizing solution or microcrystal of sorafenib was obtained. A highly aggressive HCC cell line, MHCC97-H, was used to form the subcutaneous or intra-hepatic tumor model in nude mice. Sorafenib-solution or microcrystal was injected into tumors. The clearance curve or anti-tumor efficiency of solubilizing solution or microcrystal was identified. Endogenous of EMT related indicators was identified by qPCR. RESULTS: Sorafenib slowly released in tumor tissues by sorafenib-microcrystal but not sorafenib-solution. Treatment of sorafenib-microcrystal inhibited the in vivo growth of MHCC97-H cells. CONCLUSION: The microcrystal agents of sorafenib is prepared. This work also establishes the in vivo anti-tumor efficiency of sorafenib-microcrystal on HCC cells.

BACKGROUND: The expression of long chain non-coding RNA PGM5-AS1 (lnc RNA PGM5-AS1) is reduced in peripheral blood of patients with acute immune rejection after renal transplantation. The effect of its expression on human glomerular endothelial cell (HRGEC) survival and macrophage chemotaxis remains to be studied. OBJECTIVE: To investigate the expression of lnc RNA PGM5-AS1 in serum of patients with acute rejection of renal transplantation and non-acute rejection patients and its effect on proliferation, cell cycle, apoptosis and macrophages chemotropism of HRGECs. METHODS: Forty-six patients with renal transplantation were divided into acute rejection group (n=17) and non-acute rejection group (n=29) according to whether or not acute rejection occurred within 1 month after operation. Peripheral blood sample was drawn from each patient at 1 day before operation, 1, 2, 3, and 4 weeks after operation. qRT-PCR was used to detect the expression of PGM5-AS1 in serum of patients with or without acute rejection. si-control and si-PGM5-AS1 were transfected into glomerular endothelial cells, and the expression of PGM5-AS1 in the transfected cells was detected by qPCR. MTT was used to detect cell proliferation, flow cytometry was applied to detect apoptosis and cell cycle, ELISA was adopted to detect cellular inflammatory factor secretion, and Transwell was used to detect chemotaxis of macrophages. Approval for this study was obtained from the Ethics Committee of Zhengzhou People’s Hospital, and all patients signed informed consent prior to the participation in the trial. RESULTS AND CONCLUSION: Compared with non-acute rejection patients, patients with acute rejection to renal transplantation had significantly lower PGM5-AS1 expression in serum at 1, 2, 3, and 4 weeks after transplantation (P <0.05). After PGM5-AS1 silencing, the expression of GM5-AS1 in HRGEC cells was significantly lower than that in the si-control group and normal control group (F=379.658, P < 0.05). MTT results showed that PGM5-AS1 silencing significantly inhibited HRGEC cell proliferation (P < 0.05). Flow cytometry results showed that PGM5-AS1 silencing induced HRGEC cell arrest in G0/G1 phase and increased apoptosis (P < 0.05). ELISA results showed that PGM5-AS1 silencing inhibited interleukin-13 expression and increased interleukin-6, interferon-γ and tumor necrosis factor-α expression (P < 0.05). Transwell results indicated that HRGEC cells silenced by PGM5-AS1 significantly increased the chemotaxis of macrophages (P < 0.05). All these findings indicate that PGM5-AS1 is lowly expressed in serum of patients with acute rejection of renal transplantation, and inhibition of PGM5-AS1 can promote HRGEC cell damage, which can be used as a peripheral blood diagnostic marker for early acute rejection, and may be a molecular target for the treatment of acute rejection.

Objective: To construct the competitive endogenous RNA (ceRNA) network related to gastric cancer and explore the molecular mechanism. Methods: The expression profiles of lncRNA, miRNA and mRNA in gastric cancer and paracancer tissues were analyzed by biochip technology, edgeR package in R software was used to filtrate differential expression genes (multiple change of >1.5 times, P<0.05) and volcano map was drawn. Based on the online miRNA-lncRNA prediction tool lncBase database and the miRNA Target gene prediction database (miRTarBase, target-scan, miRDB, starBase), the relationship between miRNA, lncRNA and mRNA was predicted. Cytoscape software was used to construct lncRNA-miRNA-mRNA ceRNA network and key genes (hub genes) were identified based on cytohubba calculation of degree score of each node. Then Hub genes related to the prognosis of gastric cancer were verified in the TCGA database. The GO and KEGG enrichment analysis of differentially expressed mRNA was performed using the online biological information annotation database DAVID, P<0.05 and false discovery rate (FDR)<0.05 were used as cut-off criteria. R software was used to download the RNA sequencing data and mirna-seq data of gastric cancer and adjacent tissues in TCGA database, edgeR package was used to screen out differentially expressed mRNA, miRNA and lncRNA, and some differentially expressed genes in our data were verified. In OncoLnc database, STAD project of TCGA data was selected and hub gene was input. Patients were divided into two groups based on the median value for hub genes and Kaplan-meier analysis was performed. Results: The differentially expressed 766 mRNA, 110 lncRNA and 10 miRNA were screened out, among them 90 mRNA, 4 lncRNA and 6 miRNA were used to construct the ceRNA network, and 2 of the 20 hub genes were related to the prognosis of patients. MLK7-AS1, SPP1, SULF1, hsa-miR-1307-3p were upregulated in gastric cancer tissues from our biochip, while MT2A, MT1X were downregulated, which were consistent with the results of TCGA gastric cancer database. The differentially expressed mRNAs were significantly enriched in the biological process (BP) and the mineral absorption pathway. CHST1 was negatively correlated while miR-183-5p was positively corelated with the survival of patients. Conclusion The establishment of ceRNA network for gastric cancer is conducive to further understanding of the molecular biological mechanism. CHST1 and miR-183-5p can be used as prognostic factors of gastric cancer.