A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients.

BACKGROUND: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs), as essential upstream regulators of epigenetics, play a significant role in tumorigenesis and cancer development. METHODS: CRs and immune checkpoint-related genes (ICRGs) were obtained from the previous top research. The Genome Cancer Atlas (TCGA) was utilized to acquire the mRNA expression and clinical information of patients with EC. Correlation analysis was utilized for screen CRs-related ICRGs (CRRICRGs). By Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, prognosis related CRRICRGs were screened out and risk model was constructed. The Kaplan-Meier curve was used to estimate the prognosis between high- and low-risk group. By comparing the IC50 value, the drugs sensitivity difference was explored. We obtained small molecule drugs for the treatment of UCEC patients based on CAMP dataset. RESULTS: We successfully constructed a 9 CRRICRs-based prognostic signature for patients with UCEC and found the riskscore was an independent prognostic factor. The results of functional analysis suggested that CRRICRGs may be involved in immune processes associated with cancer. Immune characteristics analysis provided further evidence that the CRRICRGs-based model was correlated with immune cells infiltration and immune checkpoint. Eight small molecule drugs that may be effective for the treatment of UCEC patients were screened. Effective drugs identified by drug sensitivity profiling in high- and low-risk groups. CONCLUSION: In summary, our study provided novel insights into the function of CRRICRGs in UCEC. We also developed a reliable prognostic panel for the survival of patients with UCEC.

A method for quantitative 2-dimensional sonographic analysis of the fetal conus medullaris position.

OBJECTIVE: This study explored the use of 2-dimensional (2D) ultrasound scans for the quantitative assessment of the fetal conus medullaris (CM) position and its correlation with gestational age (GA). METHODS: This was a prospective study. We identified the first sacral vertebra (S1) by intersection of 2 lines in 2D scans, then counted upward from S1 to determine the CM level and recorded the number of ossified sacral vertebral bodies. A quantitative assessment of the CM position was performed by measuring the distance between the CM and the midpoint of the S1 (CM-S1). The correlation between the CM-S1 distance and GA was evaluated. RESULTS: We determined the CM level by identifying S1 first in 521 fetuses (GA, 20-38 weeks). The CM position in 70% of cases was at the L2 and L2-3 level, and at the L2 level or above after 37 weeks. The number of ossified sacral veterbral bodies was not consistent. CM-S1 measurements were easy to perform. A significant positive correlation between CM-S1 distance and GA was observed (R2 = .89, P < .05). The best-fit formula was: CM-S1 distance = 1.57 × GA - 16.43. The normal reference range was established and the fifth percentile was calculated for each GA. CONCLUSIONS: S1 was easily identified, and the CM position relative to S1 was useful. There was a substantial correlation between CM-S1 and GA. Below the fifth percentile it was suggested that tethered cord may exist.

[Phenotypic and genetic analysis of a boy with 3p26.3-pter deletion and 7q31.33-qter duplication].

OBJECTIVE: To delineate the nature and origin of chromosomal copy number variants (CNVs) in a boy with mental retardation and multiple congenital malformation. METHODS: The karyotypes of the patient and his parents were analyzed with routine G-banded chromosomal analysis. Genome DNA was analyzed by next generation sequencing (NGS). RESULTS: The patient was found to harbor a structural aberration involving chromosome 3p. The karyotype of his father was 46,XY,t(3;7)(p26;q31), while his mother was found to be normal. NGS analysis of the patient revealed a 2.16 Mb microdeletion at 3p26.3-pter and a duplication at 7q31.33-qter. CONCLUSION: The structural aberration of 3p carried by the patient has derived from his father whom carried a balanced translocation of t(3;7), and his karyotype was finally determined as 46,XY,der(3) t(3;7)(p26.3;q31.33)pat. The abnormal phenotype of the patient can probably be attributed to the presence of 3p26.3-pter microdeletion and 7q31.33-qter duplication.

From clinical management to personalized medicine: novel therapeutic approaches for ovarian clear cell cancer.

Ovarian clear-cell cancer is a rare subtype of epithelial ovarian cancer with unique clinical and biological features. Despite optimal cytoreductive surgery and platinum-based chemotherapy being the standard of care, most patients experience drug resistance and a poor prognosis. Therefore, novel therapeutic approaches have been developed, including immune checkpoint blockade, angiogenesis-targeted therapy, ARID1A synthetic lethal interactions, targeting hepatocyte nuclear factor 1ß, and ferroptosis. Refining predictive biomarkers can lead to more personalized medicine, identifying patients who would benefit from chemotherapy, targeted therapy, or immunotherapy. Collaboration between academic research groups is crucial for developing prognostic outcomes and conducting clinical trials to advance treatment for ovarian clear-cell cancer. Immediate progress is essential, and research efforts should prioritize the development of more effective therapeutic strategies to benefit all patients.

Construction and validation of log odds of positive lymph nodes (LODDS)-based nomograms for predicting overall survival and cancer-specific survival in ovarian clear cell carcinoma patients.

Background: Ovarian clear cell carcinoma (OCCC) is one of the special histologic subtypes of ovarian cancer. This study aimed to construct and validate log odds of positive lymph nodes (LODDS)-based nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods: Patients who underwent surgical treatment between 2010 and 2016 were extracted from the Surveillance Epidemiology and End Results (SEER) database and the data of OCCC patients from the First Affiliated Hospital of Dalian Medical University were used as the external validation group to test the validity of the prognostic model. The best-fitting models were selected by stepwise Cox regression analysis. Survival probability was calculated by the Kaplan-Meier method, and the differences in survival time between subgroups were compared using the log-rank test. Each nomogram's performance was assessed by the calibration plots, decision curve analysis (DCA), and receiver operating characteristics (ROC) curves. Results: T stage, distant metastasis, marital status, and LODDS were identified as significant risk factors for OS. A model with four risk factors (age, T stage, stage, and LODDS value) was obtained for CSS. Nomograms were constructed by incorporating the prognostic factors to predict 1-, 3- and 5-year OS and CSS for OCCC patients, respectively. The area under the curve (AUC) range of our nomogram model for OS and CSS prediction ranged from 0.738-0.771 and 0.769-0.794, respectively, in the training cohort. The performance of this model was verified in the internal and external validation cohorts. Calibration plots illustrated nomograms have good prognostic reliability. Conclusion: Predictive nomograms were constructed and validated to evaluate the OS and CSS of OCCC patients. These nomograms may provide valuable prognostic information and guide postoperative personalized care in OCCC.

A Case Report of Retroperitoneal Ectopic Pregnancy After in vitro Fertilization-Embryo Transfer and Literature Review.

Background: Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy that can be life threatening. The pathogenesis of REP remains inconclusive and the diagnosis and treatment modalities are unclear. Case Presentation and Review of the Literature: A 27-year-old woman (gravida: 3; parturition: 0) underwent transvaginal ultrasound (TVS) 40 days after in vitro fertilization-embryo transfer (IVF-ET); no intrauterine gestational sac was detected. The patient was asymptomatic and had no abnormalities on physical examination. ß-HCG and progesterone were 18.210 mIU/mL and 10.891 ng/mL, respectively. Transabdominal ultrasound (TAS) showed that the gestational sac had implanted adjacent to the abdominal aorta and near a branch of the iliac artery. Laparoscopic exploration was performed under general anesthesia; intraoperative findings showed that the gestational sac was approximately 2.5 cm in diameter and in the same location as suggested by preoperative ultrasound. Histopathological examination confirmed the diagnosis of EP. On day three post-surgery, the levels of ß-HCG had fallen to 911 mIU/mL. We further systematically reviewed the REP cases reported in the English literature and performed a review on the diagnosis and treatment of REP. Conclusion: Clinicians should be alert to the occurrence of REP. Combined radiological examinations including ultrasonography (TAS and TVS), CT, and MRI are essential for the early diagnosis of REP. Once a definitive diagnosis is made, appropriate treatment should be administered immediately. Although there are cases of successful drug treatment described in the literature, surgery remains as the primary treatment option for REP.

Two- and three-dimensional sonographic findings of harlequin ichthyosis: case report and literature review.

BACKGROUND: Harlequin ichthyosis (HI) is a rare skin disorder with extremely high lethality due to a mutation of the ABCA12 gene. Because of its rarity and the often-late onset, prenatal screening for HI is extremely difficult, and most pregnant women might easily miss the period for optimal examinations. OBJECTIVE: To summarize the sonographic features of HI for prenatal diagnostic purposes. METHODS: The authors describe a case of HI with no family history who was diagnosed by using prenatal ultrasound scanning. The sonographic features of HI and the clinical characteristics of pregnant women were summarized by searching relevant literature over nearly two decades. RESULTS: The unique sonographic presentations including peeling skin, clenched hands and clubfeet, ectropion, flat nose, fetal growth impairment, polyhydramnios and echogenic amniotic fluid may be primarily related to skin disorders in HI fetuses. The authors also identified a novel pathogenic ABCA12 gene mutation and explained the possible pathogenic mechanisms. STUDY LIMITATIONS: Caution should be exercised in summarizing disease characteristics because of the small number of cases, and the authors are faced with the possibility of incomplete case searching. CONCLUSIONS: HI has relatively unique sonographic features. Therefore, 2D-ultrasound combined with 3D-ultrasound may be an effective method for the prenatal diagnosis of HI. Moreover, a novel pathogenic ABCA12 gene mutation may provide important clues for future research on the etiology of HI. However, the authors consider that additional studies are needed to provide more evidence for prenatal diagnosis.

[The correlation between endogenous TgAb and experimental Tg values in patients with differentiated thyroid carcinomas].

OBJECTIVE: To determine the interference of antithyroglobulin (TgAb) on the measurement of serum thyroglobulin (Tg) in patients with differentiated thyroid carcinomas (DTC). METHODS: The Tg positive serum and TgAb positive serum were taken from the patients with total thyroidectomy and thyroid remnant ablation by radioiodine. The Tg positive serum contained high level of Tg (>10 microg/L) and nondetectable TgAb. The TgAb positive serum contained high level of TgAb (>115 IU/mL) and nondetectable Tg. We incubated a constant amount of Tg with increasing volumes of Tg-free autoantibodies and allowed them to equilibrate at room temperature for 12 hours before measuring Tg and TgAb. The thyroglobulin and TgAb values were determined by the Roche electrode induce chemiluminescent emission system with monoclonal antibody sandwich analysis. The correlation between TgAb and serum Tg values was analysed. RESULTS: TgAb led to underestimation of serum Tg values by 15%-50% in 8 patients with DTC. TgAb was correlated with the magnitude of underestimated serum Tg values in 3 patients with DTC, but not in the other 5 patients with DTC. CONCLUSION: TgAb underestimated serum Tg values in a dose-dependent manner in some patients with DTC, but not in others.

Two- and three-dimensional sonographic findings of harlequin ichthyosis: case report and literature review

Abstract Background Harlequin ichthyosis (HI) is a rare skin disorder with extremely high lethality due to a mutation of the ABCA12 gene. Because of its rarity and the often-late onset, prenatal screening for HI is extremely difficult, and most pregnant women might easily miss the period for optimal examinations. Objective To summarize the sonographic features of HI for prenatal diagnostic purposes. Methods The authors describe a case of HI with no family history who was diagnosed by using prenatal ultrasound scanning. The sonographic features of HI and the clinical characteristics of pregnant women were summarized by searching relevant literature over nearly two decades. Results The unique sonographic presentations including peeling skin, clenched hands and clubfeet, ectropion, flat nose, fetal growth impairment, polyhydramnios and echogenic amniotic fluid may be primarily related to skin disorders in HI fetuses. The authors also identified a novel pathogenic ABCA12 gene mutation and explained the possible pathogenic mechanisms. Study limitations Caution should be exercised in summarizing disease characteristics because of the small number of cases, and the authors are faced with the possibility of incomplete case searching. Conclusions HI has relatively unique sonographic features. Therefore, 2D-ultrasound combined with 3D-ultrasound may be an effective method for the prenatal diagnosis of HI. Moreover, a novel pathogenic ABCA12 gene mutation may provide important clues for future research on the etiology of HI. However, the authors consider that additional studies are needed to provide more evidence for prenatal diagnosis.