Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Methods: Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. Results: A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. Conclusion: This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

LncRNA MEG3 inhibits renal fibrinoid necrosis of diabetic nephropathy via the MEG3/miR-21/ORAI1 axis.

INTRODUCTION: Diabetic nephropathy (DN) is one of the most common and lethal diabetic complications worldwide and is associated with a high risk of mortality. However, the exact mechanism behind its development is unknown. The mesangial cells (MCs) and non-coding RNAs are critical for DN, but it is unknown whether a MEG3/miR-21/ORAI1 regulatory axis exists in MCs. Hence, in this study, we aimed to understand whether the MEG3/miR-21/ORAI1 regulatory axis has a role in the pathophysiology of DN. RESULTS: We demonstrated that high-glucose stimuli downregulated MEG3 and ORAI1 expression while enhancing miR-21 expression. Exogenous miR-21 mimics inhibited ORAI1 expression, which was partially salvaged or reversed by MEG3 overexpression. Furthermore, RIP assay demonstrated that the beads labeled with AGO2 antibody could enrich more miR-21 and MEG3 than those labeled with control IgG antibody; both of them formed the RNA-induced silencing complex. Further, the biochemical indicators of db/db mice significantly improved, and renal fibrinoid necrosis was ameliorated using a miR-21 inhibitor. CONCLUSION: The MEG3/miR-21/ORAI1 axis regulates the manifestation of DN in diabetic mice and MCs, and the miR-21 inhibitor can be a potential therapeutic strategy to alleviate DN, once the presence of such an axis is found in humans.

[Endometrial microvessel density for assessing endometrial receptivity during the peri-implantation period].

OBJECTIVE: To evaluate the value of endometrial microvessel density (MVD) in assessing the endometrial receptivity during the peri-implantation period. METHODS: A total of 104 patients undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment were analyzed retrospectively. The subjects were divided into clinical pregnancy group (50 cases) and nonpregnant group (54 cases) according to the IVF-ET outcome. Endometrial tissues were collected 7 days after the natural ovulation prior to IVF-ET for measurement of the endometrial MVD using electron microscopy, which was analyzed in relation to the clinical outcome of the treatment. RESULTS: The endometrial MVD was significantly higher in the clinical pregnancy group than in the nonpregnant group [(4.12∓1.84)% vs (3.46∓1.26)%, t=-2.127, P=0.036). ROC curve analysis showed that the MVD had an area under the curve slightly over 0.5 (0.598) for predicting clinical pregnancy, suggesting a poor specificity in predicting the clinical outcome of the treatment. CONCLUSION: In IVF-ET cycles, the endometrial MVD during the peri-implantation period is helpful for assessing the endometrial receptivity, but the specificity remains low.

[Frozen embryo transfer combined with intrauterine administration of autologous peripheral blood mononuclear cells for repeated implantation failure: report of 3 cases].

OBJECTIVE: To explore the efficacy of frozen-thawed embryo transfer combined with intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) in the treatment of repeated implantation failure (RIF). METHODS: PBMCs obtained from 3 patients with RIF on the day of follicle rupture (natural cycle) or when the endometrial thickness reached 8 mm (hormone replacement cycle) were cultured in the presence of HCG for 48 h. The cultured PBMCs, along with freshly isolated PBMCs, were administered into the uterine cavity of the patients. Vitrified cleavage-stage embryos or blastocysts transfer was performed on day 3 or 5, respectively. RESULTS: Vitrified embryo or blastocyst transfer resulted in pregnancy and healthy live births in all the 3 patients. CONCLUSION: Frozen-thawed embryo transfer combined with intrauterine administration of autologous PBMCs may be an effective and safe approach to the treatment of RIF and may improve the outcomes of assisted reproduction.

[Expressions of cysteine-rich secretory protein 2 in asthenospermia].

OBJECTIVE: To investigate the mRNA and protein expression levels of cysteine-rich secretory protein 2 (CRISP2) in the sperm of asthenospermia patients, and explore their relationship with sperm motility and related molecular mechanism. METHODS: We collected 78 semen samples from adult male patients with asthenospermia and another 70 from healthy volunteers as controls. We extracted total RNA and total protein from the sperm following purification of the sperm by Percoll gradient centrifugation, and detected the relative expressions of CRISP2 mRNA and protein in the two groups by RT-PCR, SYBR Green real-time PCR and Western blot. RESULTS: The expression of CRISP2 mRNA was down-regulated by 4.3 times and that of the CRISP2 protein by 1.71 times in the asthenospermia patients, significantly lower than in the normal control group (P < 0.05). CONCLUSION: The down-regulation of CRISP2 mRNA and protein expressions in the sperm of asthenospermia patients may be closely related with decreased sperm motility, which suggests that CRISP2 may serve as a potential molecular target for the research of asthenospermia.

[Value of serum estradiol concentration in predicting the clinical outcome of IVF-ET in patients receiving long protocol of GnRHa].

OBJECTIVE: To investigate the value of serum estradiol increment and serum estradiol/follicles on the day of hCG administration in predicting the clinical outcomes of in vitro fertilization-embryo transfer (IVF-ET). METHODS: A retrospective analysis of the IVF-ET data was conducted involving 121 patients who received a long gonadotrophin-releasing hormone agonist (GnRHa) protocol. According to the increment of serum estradiol on the day of hCG administration (relative to the level on the day before hCG administration), the patients were divided into 3 groups (A1, A2 and A3) with a increment ratio below 30%, between 30% and 50%, and over 50%, respectively. In addition, according to the ratio of serum estradiol level on hCG day to mature follicle (diameter ≥ 14 mm) number, these patients were divided into three groups (B1, B2 and B3) with the ratio below 250 pg/ml, between 250 and 350 gp/ml, and over 350 pg/ml, respectively. The hormonal characteristics and clinical outcomes of the IVF-ET cycles were analyzed comparatively. RESULTS: Both the clinical pregnancy rate (71.05%) and embryo implantation rate (52.63%) were significantly higher in group A3 than in groups A1 and A2 (P<0.05). The best clinical pregnancy rate (67.86%) and embryo implantation rate (49.14%) were significantly higher in group B2 than in groups B1 and B3 (P<0.05). CONCLUSION: The variation of serum estradiol shows an important impact on the clinical outcomes of IVF-ET in patients receiving long GnRH-a protocol. Favorable outcomes can be expected with a hCG day serum estradiol increment ratio above 50% and E(2)/follicle ratio between 250 and 350 pg/ml.

[Analysis of the clinical outcomes of 160 patients undergoing repeated IVF/ICSI-ET treatment].

OBJECTIVE: To study the clinical factors affecting the outcomes of repeated assisted reproductive technology (ART) cycles. METHODS: A retrospective analysis of the clinical data and outcomes was conducted among 160 patients undergoing repeated IVF/ICSI-ET treatment between January 2006 and April 2009. RESULTS: The patients with successful clinical pregnancy after two ART cycles (group A) had a younger age and shorter duration of infertility, and had more antral follicles (AFC), more eggs and good-quality embryos with more transferred embryos available and higher good-quality embryo rate (P<0.05) than those who failed to have pregnancy after the cycles (group B). In the second cycle, the patients in group A had higher doses of short-acting GnRHa, r-HCG and HMG and at the same time more good eggs and embryos than in the first cycle. CONCLUSIONS: Female age is one of the most important factors affecting the pregnancy rate after repeated ART cycles. The clinical pregnancy rate can be enhanced by administering short-acting GnRHa, HMG, oral contraceptives and adjusting the dose of Gn as well as changing the culture medium of embryos.

[Clinical application of prefilled pen and conventional syringe during controlled ovarian stimulation for in vitro fertilization].

OBJECTIVE: To investigate the efficacy, convenience and costs of recombinant follitropin alpha administered by a prefilled pen device and conventional syringe in Chinese women undergoing controlled ovarian stimulation for in vitro fertilization (IVF). METHODS: A total of 184 patients undergoing IVF treatment were enrolled in this study. According to a long-term recombinant follicle-stimulating hormone (rFSH) protocol, ovarian stimulation was performed with the prefilled pen and conventional syringe at random in these subjects, and the dose of follitropin, number of oocytes and embryo parameters and IVF-ET outcome were compared between the two groups. RESULTS: The total rFSH dose, cost, and frequency of hospital visits were significantly lower in the pen protocol group, but the residual rFSH amount was higher. Compared with conventional injections, the prefilled pen was associated with significantly lowered rate of local redness, high rate of local bruise, more frequent follitropin dose modulation and lower serum oestradiol levels on HCG day. No significant difference was found in the endometrial thickness, numbers of oocytes retrieved, MII oocytes, transferred embryo, or the clinical pregnancy rates between the two groups. The ratio of MII oocytes, good quality embryo rates and implantation rates was significantly higher in the pen group with lower incidences of moderate and severe ovarian hyperstimulation syndrome. CONCLUSION: The prefilled pen provides an easy, safe, effective and more patient-friendly means for controlled ovarian stimulation procedure in Chinese women, but more attention should be given to protocol optimization and patient education.

[Relationship between protein oxidation levels in the follicular fluid and the outcome parameters of in vitro fertilization-embryo transplantation].

OBJECTIVE: To explore the relationship between protein oxidation levels in the follicular fluid and the outcome parameters of in vitro fertilization-embryo transplantation (IVF-ET). METHODS: The levels of advanced oxidation protein products (AOPP) in the follicular fluid were measured in 64 women with tubal infertility undergoing IVF-ET. The relationship between the AOPP levels and IVF-ET outcome parameters was analyzed. RESULTS: AOPP levels showed significant inverse correlations between the proportion of mature oocytes (r=-0.401, P=0.001), fertilization rate (r=-0.257, P=0.045), cleavage rate (r=-0.290, P=0.024) and good embryo rate (r=-0.520, P=0.000). AOPP levels differed significantly between the groups with different retrieved oocyte numbers (F=3.851, P=0.027), being the lowest in women with 8 to 15 retrieved oocytes and the highest in those with retrieved oocytes below 8. The AOPP level in the non-pregnant women was significantly higher than that in the pregnant women (t=3.665, P=0.001). The AOPP levels also differed significantly with age (F=15.919, P=0.000), and the women >35 years of age had the highest level and those below 30 years had the lowest level. CONCLUSION: Protein oxidative stress is present in the follicular fluid of women on IVF-ET cycles. High level of AOPP may have adverse effects on the oocytes and early embryonic development and may affect the outcome of IVF-ET.

[Allogeneic leukocyte immunization combined with IVF-ET for treatment of infertility induced by recurrent spontaneous abortion].

OBJECTIVE: To investigate the effect of allogeneic leukocyte immunization combined with in vitro fertilization-embryo transfer (IVF-ET) for treatment of infertility induced by habitual abortion. METHODS: Allogeneic leukocyte immunization was performed in 9 patients with infertility induced by habitual abortion, with another 9 patients undergoing IVF-ET without habitual abortion as the control group. All the patients were treated with long GnRH-a protocols. The infertility patients with recurrent spontaneous abortion history were immunized with lymphocytes from the husband for before IVF-ET and after clinical pregnancy. RESULTS: The fertilization rates of the immunotherapy group and control group were 81.3% and 82.2%, respectively, showing no significant difference (P>0.05). Five patients in each group had clinical pregnancy, and a twin pregnancy occurred in the control group. The embryo implantation rates were also comparable between the two groups (22.7% vs 28.6%, P>0.05). All the fetuses resulted from IVF-ET developed normally and were healthily delivered. CONCLUSION: Allogeneic leukocyte immunotherapy along with IVF-ET is effective for treatment of infertility resulting from recurrent spontaneous abortion.

[Expression of uncoupling protein 2 in periimplantation endometrium and its relationship with infertility].

OBJECTIVE: To study the expression of uncoupling protein 2 (UCP2) mRNA and protein in the endometrium and its changes during periimplantation period in relation to infertility. METHODS: In situ hybridation and Western blotting were used to detect 21 endometrium specimens from normal cycling women during different menstrual phases, 22 secretory endometrium specimens from infertile women and 7 decidual and chorionic villus specimens. RESULTS: UCP2 mRNA and protein were detected in the endometrium and decidua besides, the trophoblast, and UCP2 level in the endometrium increased during pregnancy. Compared with normal women, women with hydrosalpinges had significantly stronger endometrial UCP2 expression in the mid-luteal stage. CONCLUSIONS: UCP2 down-regulates reactive oxygen species and plays a role in the regulation of inflammatory events to prepare for embryo implantation. Strong endometrial UCP2 expression might be an important reason that hydrosalpinges affect embryo implantation.

[Mitochondria transfer from self-granular cells to improve embryos' quality].

OBJECTIVE: To improve embryos' quality and pregnancy rate with the method of self-mitochondria transfer. METHODS: All the 18 cases of women with repeated in vitro fertilization-embryo transfer (IVF-ET)-treatment failure or older than 37 years were treated with the long gonadotropin releasing hormone-agonist (GnRH-a) regimens. The oocytes were divided into two groups: intracytoplasmic sperm injection (ICSI) group and mitochondria transfer group if the number of the individual patients' oocytes was more than four. In mitochondria transfer group, mitochondria were prepared by different centrifugation after the granulosa cells were trimmed from the oocytes or collected from follicular fluid and homogenated. Mitochondria and immobilized sperm were injected into oocytes by micromanipulation. The fertilization rate and embryos' quality were compared. RESULTS: The fertilization rate was 74.4% in mitochondria transfer group, and 76.8% in ICSI group, with no statistical difference (P > 0.05). The good quality embryo rate in mitochondria transfer group was 59.4%, and it was 34.9% in ICSI group. The difference was significant (P < 0.05). There were 7 clinical pregnancies in the 18 cases. CONCLUSION: Self-mitochondria transfer can improve embryos' quality and pregnancy rate without influence on fertilization rate.

[Role of p38 pathway in PMA-induced in vitro invasion of JAR human choriocarcinoma cell line].

OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathways in regulating the in vitro invasion of JAR human choriocarcinoma cells induced by phorbol 12-myristate 13-acetate (PMA). METHODS: ELISA was used to detect the kinase activity of the JAR cells in response to PMA stimulation, and the in vitro invasion capabilities of the stimulated cells were observed using transwell assay. Changes in the proliferation and activity of the JAR cells cultured in vitro following PMA treatment were also observed by MTT assay. RESULTS: p38 MAPK was activated dose-dependently in JAR cells upon the stimulation by PMA, which significantly enhanced the in vitro invasion of the JAR cells, while treatment of the cells with SB203580, a specific inhibitor of p38 MAPK, inhibited the invasion of the cells. The growth of the cells, as observed from the growth curves, was not affected by the treatment of PMA and/or SB203580. CONCLUSION: Activation of p38 MAPK signal transduction pathway may enhance the invasion capability of JAR cells, and p38 MAPK inhibition may therefore yield new possibility to control the invasion of choriocarcinoma.

[Role of phorbol 12-myristate 13-acetate on cytokine expression in JAR trophoblast cell line].

OBJECTIVE: To investigate whether phorbol 12-myristate 13-acetate (PMA) modifies the invasive ability of trophoblast cells by regulating their cytokine productions. METHODS: Reverse transcriptase-polymerase chain reaction was used to examine the effect of PMA on the expression of cytokines which regulated the invasive ability of trophoblast cells. RESULTS: Prior to PMA treatment, expressions of the cytokins including hepatocyte growth factor (HGF), interleukin (IL)-1beta, insulin-like growth factor (IGF)-II, transforming growth factor (TGF)- beta and vascular endothelial growth factor (VEGF) were all detected in JAR cells, only with the exception of IGF-I. After incubation with 100 nmol/L PMA for 24 h, the cells showed strong expression of IL-1beta, HGF and IGF-II, with reduced expression of TGF-beta2 and TGF-beta3. CONCLUSION: By regulating the autocrine of these cytokines, PMA exercises its effect to enhance the invasive ability of trophoblast or choriocarcinoma cells.