Objective To investigate the relationship between the homocysteine,sperm DNA fragmentation index and sperm counts of male with severe impaired spermatoqenesis.Methods From December 2015 to February 2017,56 male patients with severe impaired spermatoqenesis were enrolled in the study.The patients were divided into two groups according to the WHO criteria:severe oligozoospermia and azoospermia group (n =25) and oligoasthenoteratozoospermia group (n =31),and the control group was a male with no reproductive impairment (n=27).The sperm parameters were analyzed by using the computer automatic semen analyzer,sperm DNA fragmentation index and serum Hcy level were detected by sperm chromatin diffusion method and enzyme colorimetric method.Results The median of Sperm DNA fragmentation index and homocysteine level in control groups were 33％ [95％CI(29.0％ ～34.4％)] and 13.2 μmol/L [95％CI(12.4 μmol/L～14.2 μmol/L)],and in severe spermatogenesis groups in these two indicators were 21％ [95％CI(19.0％ ～24.0％)] and 8.9 mol/L [95％CI(8.4 μmol/L～ 9.4 μmol/L)],respectively.The results of these two items were higher than the control group,the difference was statistically significant (t=6.793～7.543,P=0.000).Sperm survival rate in normal control group and severe spermatogenesis group was 71％ [95％ CI(67.8％ ～75.1％)] and 57％[95％CI(52.3％ ～58.0％)],respectively,and the difference was statistically significant (t=-8.475,P=0.000).Sperm DNA fragmentation index was positively correlated with serum Hcy level and sperm concentration,Passing-Bablok regression analysis was:Y=10.705 +0.053X,Y=21.071+0.286X,and Hcy level was negatively correlated with sperm concentration.Conclusion The increase of Hcy level and sperm DNA fragmentation index may be an importantcause of male with severe impaired spermatoqenesis,but the specific mechanism remains to be further studied.

Objective To study the value of serum human epididymal protein 4 (HE4) ,cytokeratin 19 frag-ment (CYFRA21-1) ,neuron-specific enolase (NES) and gastrin release precursors (Pro-GRP) in the diagnosis of female lung cancer .Methods A total of 100 cases of female lung cancer patients in the hospital were select-ed as the research object ,100 cases of benign lung diseases and 100 female health examiners as the control ,the serum levels of HE4 ,CYFRA21-1 ,NES and Pro-GRP were measured ,and the related statistical analysis was carried out .Results The serum levels of HE4 ,CYFRA21-1 ,NES and Pro-GRP in patients with lung cancer were significantly higher than those of benign lung disease and healthy control group (P<0 .05) ,and there was no significant difference between the benign lung disease group and the healthy control group (P>0 .05) . There was no significant difference in serum HE4 expression in different stages and pathological types of lung cancer (P>0 .05) .The ROC curve analysis showed that the area (AUC) of HE4 ,CYFRA21-1 and NES/Pro-GRP w ere 0 .927 ,0 .758 ,0 .652 and 0 .799 respectively ,and the best critical values w ere 63 .38 ,2 .05 ,14 .05 and 58 .50 respectively ,and the sensitivity was 88 .0％ ,80 .0％ ,60 .0％ ,71 .0％ respectively ,and the speci-ficity was 96 .0％ ,73 .0％ ,87 .0％ and 89 .0％ respectively .HE4 was obviously better than the other 3 items . Combined detection of HE4 ,CYFRA21-1 ,NES and Pro-GRP could also improve the diagnostic sensitivity of lung cancer ,which was 89 .0％ ,but the specificity had decreased by 88 .0％ .Conclusion The level of serum HE4 in female patients with lung cancer is significantly higher ,which can be used as a candidate marker for differential diagnosis of pulmonary benign and malignant diseases .The combined detection of these 4 markers has a high sensitivity for the diagnosis of female lung cancer ,which is suitable for the survey of female lung cancer in clinical .

OBJECTIVE: To study the value of plasma miRNA23-a and miRNA-451 as potential biomarkers for early diagnosis of non-small cell lung cancer (NSCLC). METHODS: Fifty patients with NSCLC and 50 healthy control subjects were recruited for testing the plasma levels of miRNA23-a and miRNA-451 and their expression levels in the tumor tissues using qRT-PCR. The correlations of the plasma levels of miRNA23-a and miRNA-451 with their expressions in the tumor tissues were analyzed. The diagnostic power of CEA, miRNA23-a and miRNA-451 for NSCLC was evaluated using the receiver-operating characteristics (ROC) curves and the area under the ROC curves (AUC). In the NSCLC cell line A549, we tested the effect of inhibition of miRNA-23a and miRNA-451 on the expression levels of SPRY2 and MIF mRNA using qRT-PCR. RESULTS: The expression levels of miRNA-23a and miRNA-451 in NSCLC tissues was significantly associated with smoking, tumor size, lymph node metastasis and TNM stage ( < 0.05). Compared with those in the control group, miRNA-23a level was significantly increased while miRNA-451 was significantly down-regulated in the tumor tissues and plasma of NSCLC patients. The plasma levels of miRNA-23a and miRNA-45 were strongly correlated with their expression levels in the tumor tissues. ROC analysis showed that for the diagnosis of NSCLC, the AUC, sensitivity and specificity of either miRNA-23a or miRNA-451 were significantly higher than those of CEA ( < 0.05). The combination of miRNA23-a and miRNA-451 markedly improved the AUC (0.900), sensitivity (78%) and specificity (86%) for the diagnosis. In A549 cells, inhibition of miRNA23-a and miRNA-451 resulted in significantly increased expression levels of SPRY2 mRNA and MIF mRNA, respectively. CONCLUSIONS miRNA-23a and miRNA-451 can be used as potential biomarkers for early diagnosis of NSCLC, and their combined detection can be more effective for the diagnosis.
Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung ; genetics ; Case-Control Studies ; Early Detection of Cancer ; Humans ; Intracellular Signaling Peptides and Proteins ; Lung Neoplasms ; genetics ; Membrane Proteins ; MicroRNAs ; ROC Curve

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor