Development and validation of a nomogram for preoperative prediction of lymph node metastasis in pathological T1 esophageal squamous cell carcinoma.

ABSTRACT: Endoscopic resection is increasingly used to treat patients with pathological T1 (pT1) esophageal squamous cell carcinoma (ESCC) because of its small surgical trauma. However, reports of the risk factors for lymph node metastasis (LNM) have been controversial. Therefore, we aim to build a nomogram to individually predict the risk of LNM in pT1 ESCC patients, to make an optimal balance between surgical trauma and surgical income.One hundred seventy patients with pT1 esophageal cancer in our hospital were analyzed retrospectively. Logistic proportional hazards models were conducted to find out the risk factor associated with LNM independently, and those were imported into R library "RMS" for analysis. A nomogram is generated based on the contribution weights of variables. Finally, decision analysis and clinical impact curve were used to determine the optimal decision point.Twenty-five (14.7%) of the 170 patients with pT1 ESCC exhibited LNM. Multivariable logistic regression analysis showed that smoking, carcinoembryonic antigen, vascular tumor thromboembolus, and tumor differentiation degree were independent risk factors for LNM. The nomogram had relatively high accuracy (C index of 0.869, 95% confidence interval: 0.794-0.914, P < .0001). The decision curve analysis provided the most significant clinical benefit for the entire included population, with scores falling just above the total score of 85 in the nomogram.Smoking, carcinoembryonic antigen, vascular tumor thromboembolus, and tumor differentiation degree may predict the risk of LNM in tumor 1 ESCC. The risk of LNM can be predicted by the nomogram.

MKRN3-mediated ubiquitination of Poly(A)-binding proteins modulates the stability and translation of GNRH1 mRNA in mammalian puberty.

The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.

[The effects of progesterone and insulin-like growth factor (IGF- I and IGF-II) on proliferation in human decidual stromal cells of early pregnancy in vitro].

OBJECTIVE: To study the effect of progesterone and Insulin-like growth factor (IGF-I and IGF-II) on proliferation in human decidual stromal cells of early pregnancy in vitro. METHODS: [3H]Thymidine (3H-TdR) uptake was applied to assess cell proliferation in human decidual stromal cells of early pregnancy (gestation of 5 to 7 weeks) in vitro after cultured with progesterone, IGF-I or IGF-II. RESULTS: Progesterone, IGF-I and IGF-II stimulated cell proliferation by 1.6-3.4 folds inhuman decidual stromal cells of early pregnancy in vitro (P<0.01), and those effects were time-dependent (P<0.01). CONCLUSION: Progesterone, IGF-I and IGF-II may play an important role in the regulation of proliferation and decidualization of stromal cells in human decidua of early pregnancy, which is essential for embryo implantation and the maintenance of early pregnancy.

[Impact of controlled ovarian hyperstimulation delayed, which occurs after functionally pituitary downregulation by depot GnRH agonist, on the outcome of in vitro fertilization and embryo transfer].

OBJECTIVE: This study observed the influence on hormone, embryos and clinical outcomes when the starting time of controlled ovarian hyperstimulation (COH) was delayed after applying a half-dose depot gonadotropin-releasing hormone agonist (GnRHa). METHODS: A total 207 cycles were divided into 3 groups: control group (98 cycles, which performed daily low dose GnRHa during the mid-luteal phase in patients' menstrual cycles and reduced the dosage to a half at the next day 3, and added gonadotropin (Gn), conventional group (63 cycles, in which pituitary desensitization was obtained with a half-dose depot GnRHa in the mid-luteal phase, and then Gn was added at day 3) and delayed group (46 cycles, having the same usage of GnRHa to conventional group, but not adding Gn until day 7). RESULTS: The cancellation rate of cycle in conventional group was the highest (P < 0.01). At the beginning of COH, serum E2 and LH levels in delayed and control group were significantly higher than those in conventional group (P < 0.01). On the day of HCG given, serum E2 level in control group was the highest (P < 0.05). LH level in delayed and control group was higher than that in conventional group (P < 0.01). Concerning the clinical efficacy and outcome, the numbers of Gn ampoules and periods for stimulation were less in delayed group than in conventional group; the numbers of retrieved and fertilized oocytes, numbers of good quality embryos, clinical pregnancy rate and embryo implantation rate in delayed and control groups were significantly more than those in conventional group (P < 0.01). In ICSI cycles, the numbers of retrieved oocytes and metaphase II oocytes in delayed and control group were more than those in conventional group. CONCLUSIONS: A half-dose depot GnRHa may produce over suppression to pituitary gland in fertilization in vitro, appropriate delay of COH starting time can decrease ovarian stimulation period and ampoules of Gn, and increase retrieved good quality oocytes, so we could achieve a larger number of good quality embryos with a good chance of implantation.

[The role of progesterone in the regulation of gene expression of insulin-like growth factor-I receptor in human decidual stromal cells of early pregnancy in vitro].

OBJECTIVE: To assess the effect of progesterone on the gene expression of insulin-like growth factor-I receptor (IGF-I R) in human decidual stromal cells of early pregnancy in vitro. METHODS: Semiquantitative reverse transcriptase polymerase chain reaction, using beta-ACTIN as internal standard, was applied to determine the levels of IGF-I R mRNA in human decidual stromal cells of early pregnancy in vitro after cultured with different concentrations of progesterone for 72 hours or cultured with 0.1 mumol/L of progesterone for different periods of time. RESULTS: The expression of IGF-I R mRNA was significantly positive in human decidual stromal cells of early pregnancy in vitro. The levels of IGF-I R mRNA were down-regulated by progesterone, and showed significant negative-correlation with the concentration of progesterone (r = -0.680, P < 0.001). The levels of IGF-I R mRNA showed no significant correlation with time when the final concentration of progesterone was 0.1 mumol/L (r = 0.005, P > 0.05). CONCLUSION: Progesterone may play an important role in the regulation of proliferation and decidualization of stromal cells by down-regulating the expression of IGF-I R mRNA in human decidual stromal cells of early pregnancy, which is important for the maintenance of early pregnancy.