Serum CXCL13 and PECAM-1 can be used as diagnostic and prognostic markers in elderly patients with gastric cancer

Purpose To investigate the application value of serum CXC Chemokine-13 (CXCL-13) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in elderly patients with gastric cancer (GC). Methods Ninety-eight elderly GC patients admitted to the Affiliated Hexian Memorial Hospital of Southern Medical University were selected as a research group, and 60 healthy subjects of the same age and in relatively good health who underwent physical examination at the same period were selected as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of CXCL13 and PECAM-1 in serum. The clinical diagnosis and prognostic value of serum CXCL13 and PECAM-1 in elderly GC patients were analyzed. Results The levels of CXCL13 and PECAM-1 in serum of the research group were significantly higher than those of the control group (P < 0.001). The AUC value of combined diagnosis of elderly GC patients by serum CXCL13 and PECAM-1 was 0.950, and that of combined evaluation of prognosis of patients was 0.849. Serum CXCL13 and PECAM-1 were significantly related to TNM staging, differentiation degree and tumor diameter in elderly GC patients (P < 0.05). High levels of CXCL13 and PECAM-1 were significantly associated with lower 5-year OS (P < 0.05). Conclusion Elderly GC patients with higher TNM staging, longer tumor diameters, high levels of CXCL13 and PECAM-1 had an increased risk of poor prognosis. Serum CXCL13 and PECAM-1 can be used as effective indicators for diagnosis and prognosis of elderly patients with GC, and can predict the 5-year OS in patients (AU)

Serum CXCL13 and PECAM-1 can be used as diagnostic and prognostic markers in elderly patients with gastric cancer.

PURPOSE: To investigate the application value of serum CXC Chemokine-13 (CXCL-13) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in elderly patients with gastric cancer (GC). METHODS: Ninety-eight elderly GC patients admitted to the Affiliated Hexian Memorial Hospital of Southern Medical University were selected as a research group, and 60 healthy subjects of the same age and in relatively good health who underwent physical examination at the same period were selected as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of CXCL13 and PECAM-1 in serum. The clinical diagnosis and prognostic value of serum CXCL13 and PECAM-1 in elderly GC patients were analyzed. RESULTS: The levels of CXCL13 and PECAM-1 in serum of the research group were significantly higher than those of the control group (P < 0.001). The AUC value of combined diagnosis of elderly GC patients by serum CXCL13 and PECAM-1 was 0.950, and that of combined evaluation of prognosis of patients was 0.849. Serum CXCL13 and PECAM-1 were significantly related to TNM staging, differentiation degree and tumor diameter in elderly GC patients (P < 0.05). High levels of CXCL13 and PECAM-1 were significantly associated with lower 5-year OS (P < 0.05). CONCLUSION: Elderly GC patients with higher TNM staging, longer tumor diameters, high levels of CXCL13 and PECAM-1 had an increased risk of poor prognosis. Serum CXCL13 and PECAM-1 can be used as effective indicators for diagnosis and prognosis of elderly patients with GC, and can predict the 5-year OS in patients.

Leptin promotes proliferation and inhibits apoptosis of prostate cancer cells by regulating ERK1/2 signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of leptin (Lep) on the proliferation, invasion and apoptosis of prostate cancer cells through the extracellular regulated protein kinase 1/2 (ERK1/2) signaling pathway. MATERIALS AND METHODS: Prostate cancer DU145 cells in the logarithmic growth phase were randomly divided into Lep (10, 20, 40, 80, 160 and 320 ng/mL) groups and blank control (Con) group. After culture, the cells were treated for 6 h, 12 h and 24 h, respectively. The effects of Lep on the proliferation and invasion of DU145 cells were detected via methyl thiazolyl tetrazolium (MTT) assay and transwell chamber assay, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to examine the messenger ribonucleic acid (mRNA) expressions of ERK1/2, b-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in DU145 cells after Lep treatment for 24 h. Thereafter, immunofluorescence assay was performed to detect the localization of ERK1/2 protein in prostate cancer DU145 cells. In addition, the expressions of phosphorylated (p)-ERK, ERK1/2 and apoptosis-related proteins, Bcl-2, Bax and cleaved cysteinyl aspartate specific proteinase (c-Caspase 3) in prostate cancer DU145 cells after treatment with different concentrations of Lep for 24 h were examined by Western blotting. RESULTS: MTT assay results showed that the proliferation rate of DU145 cells increased significantly at 6 h, 12 h and 24 h after 5-320 ng/mL of Lep treatment (p<0.05). Transwell assay manifested that the number of invasive cells was significantly raised after Lep treatment for 24 h (p<0.05). Meanwhile, the invasion ability of cells increased gradually with the elevation of Lep concentration. Subsequent qRT-PCR results demonstrated that after treatment with different concentrations of Lep, the mRNA expressions of ERK1/2 and Bcl-2 rose markedly (p<0.05). However, the mRNA expression of Bax was remarkably down-regulated (p<0.05) with the increase of Lep concentration in a concentration-dependent manner. According to the detection using a laser scanning confocal microscope, ERK1/2 red fluorescence showed punctiform aggregation, which was gradually raised with the increase of Lep concentration for 24 h. Moreover, Western blotting results denoted that with the increase of Lep concentration, the protein expressions of p-ERK, ERK1/2 and Bcl-2 were notably elevated (p<0.05), while those of Bax and c-Caspase 3 were distinctly reduced (p<0.05). CONCLUSIONS: Lep activation induces the proliferation, promotes the invasion and inhibits the apoptosis of prostate cancer cells through the ERK1/2 signaling pathway.

[Disorders of oblique muscles in horizontal strabismus].

Horizontal strabismus, the most common type of strabismus, can be complicated by the disorder of inferior oblique muscle or superior oblique muscle. It may cause problems such as compensatory head posture, vertical diplopia, torsional diplopia, and abnormal binocular fusion. In horizontal strabismus cases, the disorder of oblique muscles should be recognized, and appropriate surgical methods should be chosen, so that the best postoperative ortho and binocular vision could be obtained. (Chin J Ophthalmol, 2020, 56: 171-175).

[Comprehensive analysis of the effect of null zone shifting surgery treatment on patients with infantile nystagmus syndrome].

Objective: To characterize the postoperative change of eyes related parameters of patients with infantile nystagmus syndrome(INS), so as to provide a reference for the clinical evaluation of postoperative effect and the rational arrangement of patients' follow-up time after operation. Methods: A retrospective study. Clinical and follow-up data of 17 patients diagnosed with INS at Department of Ophthalmology in Xinhua Hospital, School of Medicine, Shanghai Jiaotong University from June 2014 to December 2016 were collected. All patients with abnormal head posture (AHP) underwent null zone shift surgery. The operative methods were Parks 5-6-7-8, Anderson, Kestenbum 5-5-6-4,null zone shift combined with strabismus correction and vertical null zone transposition. Ophthalmological examination and eye movement were recorded, including best corrected binocular visual acuity (BCBVA), position of the null zone, expanded nystagmus acuity function (NAFX) and foveation time. Single factor repeated analysis of variance, independent sample t test and rank sum test were used for statistical analysis. Results: Among the 17 children, 6 were females and 11 were males. The age at surgery of the patients was 5-11 years.The follow-up time was (14.8±6.0) months. Preoperative BCBVA was 0.382±0.147 (corrected posture), 0.300±0.056 (AHP); foveation time was (0.594±0.011)s;position of null zone was 23.570°±0.118°. The BCBVA at three months after operation was 0.318±0.044 (corrected posture), 0.260±0.045 (AHP); foveation time was (0.950±0.146)s; position of null zone was 5.360°±1.107°. The BCBVA at six months after operation was 0.264±0.039 (corrected posture), 0.230±0.037 (AHP);foveation time was (1.496±0.233) s; position of null zone was 6.070°±1.303°. The BCBVA at twelve months after operation was 0.309±0.039 (corrected posture), 0.250±0.045 (AHP);foveation time was (1.455±0.201) s; position of null zone was 9.290°±8.520°. There was statistical difference between the data of pre-operation and post-operation(all P<0.05). Change of null zone position was identified in six patients after six months.The preoperative NAFX of patients with presence of change of null zone positon was 0.308±0.063 (the primary position), 0.393±0.210 (null zone); BCBVA was 0.450±0.043 (corrected posture), 0.417±0.031 (AHP); foveation time was 0.122 (0.080-1.014)s. The postoperative NAFX of those patients was 0.430±0.090(the primary position), 0.471±0.140 (null zone); foveation time was 0.438(0.170-1.450) s. The data above were lower than that of patients with no regression of null zone[0.523±0.142,0.601±0.110,0.200±0.063,0.250±0.076,0.725(0.230-1.440)s,0.610±0.160,0.680±0.120,0.975(0.380-2.000)s]. The difference was statistically significant(all P<0.05). Conclusions: Null zone shifting surgery is an effective approach for treating INS. Reduction in the null zone position can be observed in some patients at 6 months after operation, which was related to NAFX, BCBVA and foveation time. It is recommended to extend the follow-up time to at least 6 months after the operation. (Chin J Ophthalmol, 2019, 55:13-19).

[Pay attention to the clinical classification and individualized treatment of superior oblique palsy].

Superior oblique palsy (SOP) has many anatomic variations, and the accompanied paralysis generalization could stimulate the secondary changes of other extra-ocular muscles. Therefore, the clinical manifestations of SOP can be various, and the surgical design is complicated and changeable. It is necessary to understand the clinical development, stages and types of SOP correctly, and to take into account the developmental characteristics of the superior oblique muscle and select the individualized treatment plan. In this article, the SOP manifestations, imaging features, clinical examination and personalized treatment options are discussed, in order to provide some reasonable treatment options for SOP surgery. (Chin J Ophthalmol, 2017, 53: 881-884).

[Longterm surgery outcome of Möbius syndrome].

Objective: To investigate clinical features and the long-term surgery results of Möbius syndrome patients. Methods: This investigation presents a retrospective study of Möbius syndrome in 7 children we found since 2009. All 7 patients had MRI scan, ocular alignment in primary position, the limitation of versions and ductions and forced duction under general anesthesia. Early surgery is done to the 7 esotropia children. The pre-operative and post-operative outcomes, including the ocular alignment, deviation measurements and ocular rotations, were evaluated and compared. Results: MRI showed absence of uni- or bilateral CN6 and CN7 in all 7 patients. All 7 patients underwent extra large recession of medial rectus at the first surgery, (6.17±1.47) mm/eye. Variation of ocular deviation in the primary position within 6 months postoperatively in all patients, demonstrating that strabismus surgical stabilization needs time. Three patients with esotropia deviation≥40° preoperative were under corrected and needed the secondary operations. The average deviation in the primary position was +35.00°±16.58° before surgery and +2.14°±5.67° after surgery(t=6.040, P<0.01). The abduction in affected eye is limited both pre and postoperatively and a smaller limitation of adduction after surgery. Conclusions: Möbius syndrome has been classified to congenital cranial dysinnervation disorders (CCDDs). We recommend MR recession as the first surgical choice because of the lack of abduction ability. Longterm surgical results were considered satisfactory, improving patient self-esteem and the parent satisfaction. (Chin J Ophthalmol, 2017, 53: 897-902).

[Craniosynostosis and strabismus].

Craniosynostosis(CS), the premature fusion of cranial sutures leading to an abnormal shape and precocious maturity of skull, is classified into Non-syndromic Craniosynostosis (NSC) and Syndromic Craniosynostoses(SC).NCS only has different abnormality of skull according to which cranial suture is involved while extra malformation of midface and limbs present in SCS. Common SCS contains Crouzon Syndrome, Apert Syndrome, Pfeiffer Sydrome, and etc. The clinical manifestation of CS includes malformation of skull, intracranial hypertension, brain hernia, developmental disorder of cerebral function, strabismus, and etc, while SCS has more complex manifestation. Along with the improvement of multidisciplinary cooperation, the ophthalmic complication of CS, like strabismus, is recognised by oculists gradually. This review is summarizing the clinical manifestation, complicated strabismus, pathogenesis and multidisciplinary cure of CS. (Chin J Ophthalmol, 2016, 52: 626-630).

Bibliometric network analysis of glaucoma.

Elevated intraocular pressure is recognized as the principal risk factor for development of optic nerve head (ONH) injury. Lamina cribrosa (LC) cells and astrocytes are two types of cells in the ONH. We attempted to identify more target genes and predict their underlying molecular mechanisms. In this study, we performed meta-analysis of the data from two microarray sets containing samples from LC cells and astrocytes each. Our analysis indicated that 47 differentially expressed genes (DEGs) had been identified, and 24 of them were used to construct a bibliometric network with other related genes, including GSTT1 ENO2, CPE, PTN, PTGDS, IL6, MMP1, and EGFR. Further, our results predicted these genes might be involved in glaucoma development through Toll-like receptor signaling pathway, ErbB signaling pathway, and glioma and other cancer-related pathways. Therefore our study provides potential target genes and pathways for future therapeutic studies of glaucoma.

Estradiol prevents amyloid-beta peptide-induced cell death in a cholinergic cell line via modulation of a classical estrogen receptor.

The pathology of Alzheimer's disease includes amyloid-beta peptide aggregation that contributes to degeneration of cholinergic neurons. Even though the underlying molecular mechanisms remain unclear, recent in vitro evidence supports a protective role for estrogens against several neurotoxic agents. Here we report that, in a murine cholinergic cell line (SN56), the massive cell death induced by 1-40 fragment of amyloid-beta peptide was prevented by 17beta-estradiol through a mechanism that may involve estrogen receptor activation. The protective effect of estradiol was observed in a dose-dependent manner, and was completely blocked by the pure antiestrogen ICI 182,780. In contrast, the inactive isomer 17alpha-estradiol consistently showed weaker neuroprotection than the native hormone that was unaffected by ICI 182,780 treatment. In addition, equivalent concentrations of 17beta-estradiol enhanced luciferase activity in cells transfected with a luciferase reporter gene driven by tandem estrogen response elements. Estrogen-induced luciferase activity was blocked by ICI 182,780, indicating estrogen receptor-dependent transcriptional activity. We also observed by reverse transcription-polymerase chain reaction, Western blot and immunocytochemistry that increasing concentrations of 17beta-estradiol enhanced the expression of estrogen receptor alpha mRNA and protein during amyloid-beta-induced toxicity. Under these conditions, it was found by confocal microscopy that the localization of estrogen receptor alpha in the absence of hormone was mainly extranuclear. However, the receptor was consistently observed also at the nuclear region after estrogen exposure. Overall, these data suggest that estrogen may exert neuroprotective effects against amyloid-beta-induced toxicity by activation of estrogen receptor-mediated pathways. In addition, intracellular estrogen receptors are up-regulated by their cognate hormone even during exposure to neurotoxic agents.

Inactivation of the RAD1 excision-repair gene does not affect correction of mismatches on heteroduplex plasmid DNA in yeast.

The efficiency and direction of mismatch correction in the Saccharomyces cerevisiae SUP4-o gene were not altered by an excision-repair defect (rad1). Although excision-repair functions remove methylated adenine from yeast, adenine methylation at a GAC sequence in SUP4-o did not direct the correction of mismatches via excision repair.

Elimination of the yeast RAD6 ubiquitin conjugase enhances base-pair transitions and G.C----T.A transversions as well as transposition of the Ty element: implications for the control of spontaneous mutation.

The RAD6 gene of the yeast Saccharomyces cerevisiae encodes an enzyme that conjugates ubiquitin to other proteins. Defects in RAD6 confer a mutator phenotype due, in part, to an increased rate of transposition of the yeast Ty element. To further delineate the role of protein ubiquitination in the control of spontaneous mutagenesis in yeast, we have characterized 202 mutations that arose spontaneously in the SUP4-o gene carried on a centromere vector in a RAD6 deletion strain. The resulting mutational spectrum was compared to that for 354 spontaneous SUP4-o mutations isolated in the isogenic wild-type parent. This comparison revealed that the rad6 mutator enhanced the rate of single base-pair substitution, as well as Ty insertion, but did not affect the rates of the other mutational classes detected. Relative to the wild-type parent, Ty inserted at considerably more SUP4-o positions in the rad6 strain with a significantly smaller fraction detected at a transposition hotspot. These findings suggest that, in addition to the rate of transposition, protein ubiquitination might influence the target site specificity of Ty insertion. The increase in the substitution rate accounted for approximately 90% of the rad6 mutator effect but only the two transitions and the G. C----T.A transversion were enhanced. Analysis of the distribution of these events within SUP4-o suggested that the site specificity of the substitutions was influenced by DNA sequence context. Transformation of heteroduplex plasmid DNAs into the two strains demonstrated that the rad6 mutator did not reduce the efficiency of correcting mismatches that could give rise to the transitions or transversion nor did it bias restoration of the mismatches to the incorrect base-pairs. These results are discussed in relation to possible mechanisms that might link ubiquitination of proteins to spontaneous mutation rates.

The yeast rad18 mutator specifically increases G.C----T.A transversions without reducing correction of G-A or C-T mismatches to G.C pairs.

Inactivation of the Saccharomyces cerevisiae RAD18 gene confers a mutator phenotype. To determine the specificity of this effect, a collection of 212 spontaneous SUP4-o mutants arising in a rad18 strain was characterized by DNA sequencing. Comparison of the resulting mutational spectrum with that for an isogenic wild-type (RAD18) strain revealed that the rad18 mutator specifically enhanced the frequency of single base pair substitutions. Further analysis indicated that an increase in the frequency of G.C----T.A transversions accounted for the elevated SUP4-o mutation frequency. Thus, rad18 is the first eucaryotic mutator found to generate only a particular base pair substitution. The majority of G.C pairs that were not mutated in the rad18 background were at sites where G.C----T.A events can be detected in SUP4-o, suggesting that DNA sequence context influences the rad18 mutator effect. Transformation of heteroduplex plasmid DNAs into the two strains demonstrated that the rad18 mutator did not reduce the efficiency of correcting G-A or C-T mismatches to G.C pairs or preferentially correct the mismatches to A.T pairs. We propose that the RAD18 gene product might contribute to the fidelity of DNA replication in S. cerevisiae by involvement in a process that serves to limit the formation of G-A and C-T mismatches at template guanine and cytosine sites during DNA synthesis.

Specificity of the mutator effect caused by disruption of the RAD1 excision repair gene of Saccharomyces cerevisiae.

Disruption of RAD1, a gene controlling excision repair in the yeast Saccharomyces cerevisiae, increased the frequency of spontaneous forward mutation in a plasmid-borne copy of the SUP4-o gene. To characterize this effect in detail, a collection of 249 SUP4-o mutations arising spontaneously in the rad1 strain was analyzed by DNA sequencing. The resulting mutational spectrum was compared with that derived from an examination of 322 spontaneous SUP4-o mutations selected in an isogenic wild-type (RAD1) strain. This comparison revealed that the rad1 mutator phenotype was associated with increases in the frequencies of single-base-pair substitution, single-base-pair deletion, and insertion of the yeast retrotransposon Ty. In the rad1 strain, the relative fractions of these events and their distributions within SUP4-o exhibited features similar to those for spontaneous mutagenesis in the isogenic RAD1 background. The increase in the frequency of Ty insertion argues that Ty transposition can be activated by unrepaired spontaneous DNA damage, which normally would be removed by excision repair. We discuss the possibilities that either translesion synthesis, a reduced fidelity of DNA replication, or a deficiency in mismatch correction might be responsible for the majority of single-base-pair events in the rad1 strain.