Genomic characterization of peritoneal lavage cytology-positive gastric cancer.

Objective: Positive peritoneal lavege cytology (CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1 and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer. Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31 matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer. Results: Least absolute shrinkage and selection operator (LASSO) algorithm identified 43 cytology-positive marker genes, while MutSigCV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology (CY0). Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1 and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Variation Patterns of Hemoglobin Levels by Gestational Age during Pregnancy: A Cross-Sectional Analysis of a Multi-Center Retrospective Cohort Study in China.

BACKGROUND: Pregnancy anemia is a global health concern. However, to our knowledge, there still has little consensus on the reference value of hemoglobin levels. Particularly, little evidence from China was accessible in most existing guidelines. OBJECTIVE: To evaluate hemoglobin levels and anemia prevalence of pregnant women in China and offer evidence for anemia and its reference values in China. METHODS: A multi-center retrospective cohort study was conducted among 143,307 singleton pregnant women aged 15-49 at 139 hospitals in China, with hemoglobin concentrations routinely tested at each prenatal visit. Subsequently, a restricted cubic spline was performed to reveal a non-linear variation of hemoglobin concentrations during the gestational week. The Loess model was used to describe the changes in the prevalence of different degrees of anemia with gestational age. Multivariate linear regression model and Logistic regression model were applied to explore influencing factors of gestational changes in hemoglobin level and anemia prevalence, respectively. RESULTS: Hemoglobin varied nonlinearly with gestational age, and the mean hemoglobin levels decreased from 125.75 g/L in the first trimester to 118.71 g/L in the third trimester. By analyzing hemoglobin levels with gestational age and pregnancy period, we proposed new criteria according to 5th percentile hemoglobin concentration in each trimester as a reference for anemia, with 108 g/L, 103 g/L, and 99 g/L, respectively. According to WHO's criteria, the prevalence of anemia sustainably increased with gestational age, with 6.2% (4083/65,691) in the first trimester, 11.5% (7974/69,184) in the second trimester and 21.9% (12,295/56,042) in the third trimester, respectively. In subsequent analysis, pregnant women in non-urban residents, multiparity, and pre-pregnancy underweight tended to have lower hemoglobin levels. CONCLUSIONS: This research, the first large-sample study to present a set of gestational age-specific reference centiles for hemoglobin levels in China, could be used to obtain a better understanding of the overall levels of hemoglobin in Chinese healthy pregnant women and ultimately offer clues for a more precise hemoglobin reference value of anemia in China.

An Evaluation of Exposure to 18 Toxic and/or Essential Trace Elements Exposure in Maternal and Cord Plasma during Pregnancy at Advanced Maternal Age.

Pregnant women of advanced maternal age (AMA) are vulnerable to exposure to the surrounding environment. Assessment of trace elements in pregnant women living in specific areas is important for biomonitoring. However, exposure levels and variation patterns during pregnancy remains controversial and attracts extensive public concern. Therefore, we aimed to evaluate exposure of 18 toxic and/or essential trace elements in maternal plasma and in paired cord plasma during pregnancy at AMA. A total of 48 pregnant women of AMA were recruited in Peking University Third Hospital from 2018 to 2021. Eighteen elements found in maternal plasma during the 1st, 2nd, or 3rd trimester of pregnancy and paired cord plasma were measured by 7700x ICP-MS (Agilent Technologies, Palo Alto, CA, USA) and Elan DRC type II ICP-MS (The Perkin-Elmer Corporation, Waltham, MA USA). Concentrations of Pb, Se, Fe, Zn, and Mo all decreased during pregnancy, while Cu increased. Interestingly, concentrations of Rb decreased initially but then increased. Elements as Al, Co, Se, Cu, and Ni showed significantly lower levels in cord than in maternal plasma, while elements as Sr, Fe, Rb, Mn and Zn displayed significantly higher levels in cord than in maternal plasma. Moreover, positively- interacted clusters were found in Ni-Co-Cu-Al-Rb-Zn and Zn-Mn-Al-Pb in maternal blood. Similar positively-interacted clusters were found in Zn-Ni-Co, Zn-Ni-Fe, Mn-Al-Pb, Fe-Pb-Mn, Fe-Ni-Cu, and Rb-Cu-Sb-Fe-Mn in cord plasma. Furthermore, correlations between paired maternal and cord blood samples for As, Sr, and Mo were statistically significant, indicating that the fetus burden may reflect maternal exposure to some extent. Admittedly, levels of toxic and essential elements in our cohort study were comparatively lower than those in the scientific literature.