Associations of maternal serum concentration of iron-related indicators with gestational diabetes mellitus in Chinese: A pilot prospective cohort study.

BACKGROUND: We aimed to provide a comprehensive understanding of the associations between iron metabolism and gestational diabetes mellitus (GDM) by examining multiple iron-related indicators. METHODS: We conducted a prospective study involving 907 Chinese pregnant women. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of iron-related indicators during the first trimester (≤ 14 weeks of gestation). GDM outcomes were measured through oral glucose tolerance tests (OGTT) conducted between weeks 24 and 28 of gestation. RESULTS: Subjects with iron-related indicators below the 10th percentile (except for serum iron and soluble transferrin receptor) had a higher risk of GDM compared to normal subjects (10th-90th percentiles). The ORs (95 %CI; p-value) were 1.88 (1.10, 3.20; P=0.020) for ferritin, 1.88 (1.10, 3.19; P=0.020) for hepcidin. Higher levels of ferritin (> 90th percentile) were associated with a higher risk of abnormal fasting blood glucose, while lower levels (< 10th percentile) of ferritin, hepcidin, and transferrin were associated with a higher risk of one-hour postprandial glucose ≥ 8.6 mmol/L in the OGTT. CONCLUSIONS: Lower levels (< 10th percentiles) of several iron-related indicators (ferritin, hepcidin, and transferrin) were associated with a higher risk of GDM and abnormal blood glucose compared to normal subjects.

Thermal Proteome Profiling Strategy Identifies CNPY3 as a Cellular Target of Gambogic Acid for Inducing Prostate Cancer Pyroptosis.

There is an urgent requirement to acquire a comprehensive comprehension of novel therapeutic targets for prostate cancer to facilitate the development of medications with innovative mechanisms. In this study, we identified gambogic acid (GBA) as a specific pyroptosis inducer in prostatic cancer cells. By using a thermal proteome profiling (TPP) strategy, we revealed that GBA induces pyroptosis by directly targeting the canopy FGF signaling regulator (CNPY3), which was previously considered "undruggable". Moreover, through the utilization of the APEX2-based proximity labeling method, we found that GBA recruited delactatease SIRT1, resulting in the elimination of lysine lactylation (Kla) on CNPY3. Of note, SIRT1-mediated delactylation influenced the cellular localization of CNPY3 to promote lysosome rupture for triggering pyroptosis. Taken together, our study identified CNPY3 as a distinctive cellular target for pyroptosis induction and its potential application in prostate cancer therapy.

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study.

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

Safety and efficacy study of lung cancer stem cell vaccine.

In this trial, lung cancer stem cells (CSCs) were separated and cultured to produce a vaccine; its safety and efficacy were prospectively evaluated in low-, medium-, and high-dose groups. Between February and September 2014, we enrolled 90 patients who met the enrollment criteria and assigned them to three groups (n = 30). Throughout the trial, injection site reaction was the most common reaction (63 %), and fever was least common (16 %); however, there was no difference among the three groups. When the immune responses pre- and post-vaccination were compared, we found that the CSC-nonspecific and CSC-specific responses were both significantly enhanced in the medium- and high-dose groups. This study is the first clinical trial of a lung CSC vaccine and preliminarily proves its safety and efficacy.

Sequential use of transarterial chemoembolization and percutaneous cryosurgery for hepatocellular carcinoma.

AIM: To evaluate the efficacy of sequential use of transarterial chemoembolization (TACE) and percutaneous cryosurgery for unresectable hepatocellular carcinoma (HCC). METHODS: Four hundred and twenty patients were enrolled in this study. The patients, who were considered to have unresectable tumors due to their location or size or comorbidity, were divided into sequential TACE-cryosurgery (sequential) group (n = 290) and cryosurgery alone (cryo-alone) group (n = 130). Patients in the sequential group tended to have larger tumors and a greater number of tumors than those in the cryo-alone group. Tumors larger than 10 cm in diameter were only seen in the sequential group. TACE was performed with the routine technique and percutaneous cryosurgery was conducted under the guidance of ultrasound 2-4 wk after TACE. RESULTS: During a mean follow-up period of 42 +/- 17 mo (range, 24-70 mo), the local recurrence rate at the ablated area was 17% for all patients, 11% and 23% for patients in sequential group and cryo-alone groups, respectively (P = 0.001). The overall 1-, 2-, 3-, 4- and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1- and 2-year survival rates (71% and 61%) in sequential group were similar to those (73% and 54%) in cryo-alone group (P = 0.69 and 0.147), while the 4- and 5-year survival rates were 49% and 39% in sequential group, higher than those (29% and 23%) in cryo-alone group (P = 0.001). Eighteen patients with large HCC (> 5 cm in diameter) survived for more than 5 years after sequential TACE while no patient with large HCC (> 5 cm in diameter) survived more than 5 years after cryosurgery. The overall complication rate was 24%, and the complication rates were 21% and 26% for the sequential and cryo-alone groups, respectively (P = 0.06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P = 0.02). Liver crack only occurred in two patients of the cryo-alone group. CONCLUSION: Pre-cryosurgical TACE can increase the cryoablation efficacy and decrease its adverse effects, especially bleeding. Sequential TACE and cryosurgery may be the better procedure for unresectable HCC, especially for large HCC.