AIM: To investigate the effect of CP466722, an inhibitor of ataxia telangiectasia mutated protein (ATM), on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells.METHODS: The cell viability was detected by MTT assay.The cell growth inhibition was measured by colony formation assay.The effect of CP466722 on the cell cycle distribution of the HepG2 cells was examined by flow cytometry.The cell apoptosis was analyzed by TUNEL staining.The protein expression was examined by Western blotting.RESULTS: CP466722 inhibited the cell viability and cell proliferation in a dose-dependent manner.In CP466722-treated HepG2 cells, the cell cycle was arrested in G2/M phase, and the protein levels of phosphorylated cell division cycle protein 2 (p-Cdc2), cell division cycle protein 25C (Cdc25C) and phosphorylated Cdc25C (p-Cdc25C) were inhibited, whereas the protein expression of p27 was up-regulated.CP466722 triggered the apoptosis of HepG2 cells through cleavages of caspase-3 and poly (ADP-ribose) polymerase (PARP).In addition, CP466722 increased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and suppressed the expression of β-catenin and survivin in the HepG2 cells.CONCLUSION: CP466722 inhibits the proliferation and induces the apoptosis of HepG2 cells, which may be related to activating p38 MAPK and inhibiting the expression of β-catenin and survivin.

Objective To investigate the effects of intravitreous injection of conbercept for macular edema secondary to retinalvein occlusion(RVO) during 6 months period.Methods A retrospective clinical study.34 patients (34 eyes) were included in this study,who were diagnosed with macular edema due to retinal vein occlusion by ophthalmologic examination,fundus photography,optical coherence tomography (OCT),fundus fluorescein angiography and other methods.The best corrected visual acuity (BCVA) was examined using the international standard visual acuity chart,and the results were converted to the logMAR visual acuity.The average logMAR BCVA was 0.90 ± 0.68,and the mean macular central retinal thickness (CMT) was (672.27±227.51) μm before treatment.All subjects received intravitreal injection of 0.5 mg conbercept (0.05 ml) at the first visit.Injections were repeated based on the visual acuity changes and the OCT findings.34 eyes received 69 times of injection,the average number of injections was 2.03 ± 1.03.BCVA,OCT were examined before and after treatment using the same method.BCVA and CMT changes,drugs and treatments associated cardiac and cerebral vascular accident,intraocular pressure elevation,retinal tears,retinal detachment,endophthalmitis and other complications after treatment were observed.Linear correlation analysis was used to analyze the correlation between prognosis BCVA and baseline BCVA,correlation between prognosis BCVA and baseline CMT,and also correlation between BCVA and CMT at different time points before and after treatment.Results At 1 week and 1,2,3,6 months after treatment,the average logMAR BCVA was 0.65±0.61,0.56±0.61,0.46±0.55,0.56±0.71,0.44±0.48 respectively.During 1,2,3,6 months after treatment,the mean logMAR BCVA were improved with statistically significant difference (Z=34.029,47.294,41.338,43.603;P＜0.05),while 1 week after treatment showed no obvious improvement (Z=21.941,P＞0.05).At 1 week and 1,2,3,6 months after treatment,the average CMT was (285.89 ± 96.69),(256.65 ± 143.39),(278.68 ± 156.92),(290.11 ± 188.17),(217.15 ± 48.04) μm respectively.At 1 week and 1,2,3,6 months after treatment,the mean CMT were all decreased with statistically significant difference (Z=68.500,98.735,93.235,91.132,109.162;P＜0.05).There was a positive correlation between the prognosis visual acuity and preoperative visual acuity (r=0.682,P＜0.05).However,there was no correlation between the prognosis vision and the degree of macular edema before treatment (r=0.078,P＞0.05).Before and 3,6 months after treatment,BCVA was negatively correlated with CMT (r=0.491,0.416,0.386;P＜0.05),while there was no correlation in other time points (r =0.145,0.217,0.177;P＞ 0.05).Systemic adverse reactions and persistent intraocular pressure elevation,iatrogenic cataract,retinal detachment,retinal tear,endophthalmitis and ocular complications were never found in the follow-up period.Conclusion Intravitreal conbercept is a safe and effective approach for RVO,which can significantly improve visual acuity and reduce CMT.

Objective To explore the feasibility of intravoxel incoherent motion DWI (IVIM-DWI) in differential diagnosis of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH).Methods A total of 407 patients with clinically-suspected HCC or FNH underwent conventional and dynamic enhanced MRI and IVIM-DWI,60 patients (40 cases of HCC,20 cases of FNH) were enrolled.Parameters of ADC,slow apparent diffusion coefficient (D),fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f) were obtained by monoexponential model and biexponential model respectively.Results The values of ADC,D,D* and f in FNH group were (1.60±-0.25) × 10-3mm2/s,(1.12±0.17)×10-3mm2/s,(44.89±18.23)× 10-3 mm2/s and (34.80 ± 9.68)％,and those in HCC group were (1.32 ± 0.21) × 10-3 mm2/s,(0.82±-0.21) × 10-3mm2/s,(49.82±20.11) × 10 3mm2/s and (28.72±13.84) ％,respectively.Significant inter-group differences were observed in ADC and D (both P＜0.001),however,there were no significant differences in D* and f (both P＞0.05).The areas under the ROC curve of D were 0.90,and taking D=0.96 × 10-3 mm2/s as cut-off value,the sensitivity and specificity of D in diagnosis of HCC were 84.44％ and 90.02％.Conclusion IVIM-DWI is useful to distinguish FNH from HCC,and the D value in biexponential model has the best diagnostic efficacy for differentiations.

Objective:To discuss the influence of bifid triple viable enteric-coated capsules on liver function and inflammatory fac-tor in the patients with non-alcoholic steatohepatitis ( NASH) . Methods:Totally 70 cases of patients with NASH were selected and di-vided into the control group and the observation group at random. The patients in the two groups were all given routine hepatoprotective therapy. The patients in the observation group were additionally given 420mg bifid triple viable enteric-coated capsules, three times a day for 4 weeks. Except for bifid triple viable enteric-coated capsules, the patients in the control group were given the same medical treatment as that in the observation group. The changes of liver function index, serum high sensitivity C reaction protein ( hs-CRP) , IL-6 and IL-8 levels in the two groups before and after the medical treatment were observed and the security was compared. Results:After the 4-week medical treatment, ALT, GGT, serum hs-CRP, IL-6 and IL-8 levels in the two groups were obviously declined than those before the treatment (P<0. 05 or P<0. 01), and the declining rate in the observation group was much higher than that in the control group (P<0. 05). Totally 6 and 4 cases of adverse drug reaction (ADR) respectively appeared in the observation group and the control group during the medical treatment with mild symptom, and the difference was without statistical significance (P>0. 05). Conclusion:Bifid triple viable enteric-coated capsules in the treatment of NASH can obviously reduce the serum hs-CRP, IL-6 and IL-8 levels, inhibit the intrahepatic inflammation and immunologic injury, and improve the liver function index with high security.

Objective To study interleukin-23 (IL-23) levels in serum and dendritic cells of acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B (CHB) and to explore its relationship with the prognosis.Methods Peripheral blood mononuclear cells and serum were collected from 40 ACLF patients with CHB (including survival group 27 cases and non-survival group 13 cases) and 26 healthy controls.Monocytes were induced to immature dendritic cell in vitro and TNF-α was added to induce dendritic cell maturation.IL-23 mRNA of dendritic cells was detected by real time polymerase chain reaction (PCR), and serum IL-23 level was measured by enzyme-linked immuno sorbent assay (ELISA).Differences among the parameters with normal distribution were compared using t test, those with non-normal distribution were compared using non-parametric Mann-Whitney U-test, and the relationship between two variables was assessed by Spearman′s rank correlation.Results International normalized rate (INR) and model for end-stage liver disense (MELD) scores in non-survival group of ACLF were higher than those in survival group (INR: 2.32 vs 1.64, U=69.00, P=0.002 2;MELD:36 vs 30, U=64.50, P=0.001 4).However, there were no significant differences between two groups at gender, age, alanin aminotransferase (ALT), aspartate aminotrans ferase (AST), bilirubin, creatinine, hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and serum IL-23.IL-23 mRNA level in dendritic cells at baseline in non-survival group of ACLF was significantly higher than that in survival group (76 vs 43, U=71.50, P=0.002 8).After treatment, serum IL-23 was significantly declined in survival group ([160±75] ng/L vs [91±49] ng/L, t=4.012, P=0.000 2), but not in non-survival group.Significant positive correlation was observed between IL-23 mRNA level in dendritic cells and MELD score at baseline (r=0.7198,P<0.01).Conclusions Persistent high serum IL-23 level suggests poor prognosis in ACLF patients with CHB.IL-23 mRNA expression in dendritic cells has good consistency with MELD score and the patients with high IL-23 mRNA expression has poor outcome.

Objective:To investigate the effects of Rad50-targeted inhibition on the radiosensitivity of head and neck squamous cell carcinoma cells.Methods:Rad50 in Tca8113 and OSCC-15 cells was down-regulated by siRNA.Then the cells were treated by a small dose of radiation(2 Gy),Western blot was used to detect the expression of Rad50 protein.Comet assay was used to evaluate the DNA double strand breaks(DSBs).Colony survival assay was performed to detect the survival rate of the cells.Telomere FISH was performed to assess the telomere length in the cells.Results:Target siRNA inhibited Rad50 protein expression in Tca8113 and OSCC-15 cells. siRNA combined with the radiation of 2 Gy produced more DSBs,decreased the proliferation and shortened the nucleus telomere length of the cells more than radiation treatment alone.Conclusion:The targeted inhibition of Rad50 may increase the radiosensitivity of Tca8113 and OSCC-15 cells.

Objective To investigate whether chemokine CCL2(also known as monocyte chemotactic protein 1 or MCP-1)has a causal relationship with lung cancer.Methods Genetic data of chemokine CCL2 and different pathological subtypes of lung cancer were extracted from genome-wide association studies(GWAS),and inverse-variance weighted(IVW)analysis was used as main analysis,while weighted median,simple model,MR-Egger regression,and weighted model were chosen as supplementary analyses.Sensitivity analyses were performed to verify the reliability of the data.Results The result of IVW analysis on chemokine CCL2 to lung adenocarcinoma was OR = 1.065,95%CI(0.919～1.234),P = 0.401.The result of IVW analysis on chemokine CCL2 to squamous cell lung carcinoma was OR = 1.059,95%CI(0.931～1.205),P = 0.381.The result of IVW analysis on chemokine CCL2 to small cell lung carcinoma was OR = 0.959,95%CI(0.760～1.208),P = 0.720.Conclusions There is no direct causal relationship between chemokine CCL2 and lung cancer.

BACKGROUND/AIMS: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0–S2 (early fibrosis) from S3–S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. METHODS: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0–S2 from S3–S4. RESULTS: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0–S2 to S3–S4 (p < 0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0–S2 from S3–S4, with an area under the curve of 0.936. CONCLUSIONS: The levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0–S2 from S3–S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.
Biomarkers ; Biopsy ; Early Diagnosis* ; Fibrosis ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Liver Cirrhosis* ; Liver* ; Logistic Models ; MicroRNAs* ; Polymerase Chain Reaction ; ROC Curve

Glycosphingolipids (GSLs) are widely distributed in the phospholipid bilayer of various cell membranes, which play an important role in maintaining cell membrane stability, and regulate various cellular processes including adhesion, proliferation, apoptosis and recognition, as well as participate in various cellular activities. In addition, GSLs are not only involved in the process of apoptosis, but also regulate multiple signals in tumorigenesis and tumor development. The tumor-associated GSLs are expected to be used as diagnostic markers and immunotherapeutic targets for malignant tumors. These findings have important implications for the study of apoptosis and provide the new direction of tumor therapy. This review summarized the latest research progress of GSLs-mediated apoptosis and its effect on the genesis, development and metastasis of tumor cells. Moreover, we discussed the metabolic pathway of GSLs-mediated apoptosis and its application in tumor therapy, as well as the development prospect of targeted therapy strategies based on GSLs.
Humans ; Glycosphingolipids/metabolism* ; Apoptosis ; Cell Membrane ; Neoplasms/metabolism*

Objective:To explore the difference of the vessel and plaque characteristics, myocardial perfusion and cardiac function between patients with ischemia with non-obstructive coronary artery disease (INOCA) and obstructive coronary artery disease (CAD).Methods:From July 2021 to June 2022, 101 patients with angina were referred to dynamic computed tomography myocardial perfusion (CTP) and coronary computed tomography angiography (CCTA) and retrospectively included in our hospital. Based on the results of CTP and CCTA, patients were divided into INOCA (27 cases), moderate obstructive CAD (26 cases) and severe obstructive CAD (48 cases). The anatomical coronary artery stenosis, plaque characteristics and myocardial perfusion features of all patients were analyzed. Furthermore, left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained on full-phase reconstruction CCTA image by using Medis Suite 3.2 postprocessing software. Multigroup analysis used one way ANOVA or Kruskal Wallis H test. Results:Patients with INOCA were younger than patients with moderate and severe obstructive CAD ( P<0.001). INOCA patients (7.4%, 2/27) had lower rate of positive remodeling than both moderate (57.7%, 15/26, P<0.001) and severe obstructive CAD patients (33.3%, 16/48, P=0.017). The percentage of ischemic myocardium volume in patients with INOCA were similar with those in patients with severe CAD (all P>0.05), but significantly higher than those in patients with moderate CAD (all P<0.05). No significant difference in terms of GLS was detected between patients with INOCA [-17.4% (-21.6%, -11.6%)] and severe CAD [-17.6% (-21.9%, -14.8%), P=0.536], however, patients both with INOCA and severe CAD also had higher GLS than patients with moderate obstructive CAD [-22.3% (-29.8%, -19.0%), all P<0.05]. Conclusions:Based on"one-stop-shop"CTP combined with CCTA imaging, early cardiac functional changes including abnormal myocardial perfusion and myocardial strain in INOCA patients were similar to those in patients with severe obstructive CAD and more severe than those in patients with moderate obstructive CAD.