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.

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 early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study.

Background and Aims: The association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study. Methods: We included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia. Results: After adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1. Conclusion: Higher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women.

Associations between thyroid function and gestational diabetes mellitus in Chinese pregnant women: a retrospective cohort study.

BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.

Early pregnancy vitamin D and the risk of adverse maternal and infant outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence has suggested that lower gestational vitamin D levels might increase the risks of adverse pregnancy and birth outcomes. The results remain inconsistent and require further exploration. METHODS: A total of 2814 Chinese mother-infant pairs were included in this retrospective cohort study. Serum concentrations of 25(OH)D were reviewed in early pregnancy (16.3 ± 2.3 weeks). Outcomes of maternal gestational diabetes mellitus (GDM), cesarean section, fetal distress, preterm birth, low birth weight (LBW), and macrosomia were extracted from the medical records. Cox regression analysis was used to explore these associations. RESULTS: In total, 19.3% of mothers were pregnant at an advanced age (≥35 years), and 40.3% of pregnant women had vitamin D deficiency (< 50 nmol/L). After adjusting for potential covariates, the hazard ratio (HR) (95% CI) per standard deviation (SD) increase of serum 25(OH)D concentrations was 0.86 (0.779, 0.951) for GDM, 0.844 (0.730, 0.976) for preterm birth, and 0.849 (0.726, 0.993) for LBW. Similar protective associations were found for GDM, cesarean section, and preterm birth for a better vitamin D status when compared with vitamin D deficiency. CONCLUSION: Higher early pregnancy vitamin D was associated with a lower risk of GDM, cesarean section, preterm birth, and LBW.

Associations Between Maternal Thyroid Function and Birth Outcomes in Chinese Mother-Child Dyads: A Retrospective Cohort Study.

Objective: Although research suggests a close association between maternal thyroid function and birth outcomes, no clear conclusion has been reached. We aimed to explore this potential association in a retrospective cohort study. Methods: This study included 8985 mother-child dyads. The maternal serum free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab) concentrations and birth outcome data were reviewed from medical records. Subjects with TPO Ab concentrations of >34 and ≤34 IU/ml were classified into the TPO Ab positivity (+) and TPO Ab negativity (-) groups, respectively. Results: Compared with subjects in the normal group (0.1 ≤ TSH < 2.5 mIU/L and TPO Ab-), those with TSH concentrations of 2.5-4.0 mIU/L and TPO Ab- had a 0.65-fold lower risk of low birth weight (LBW). In contrast, those with TSH concentrations of >4.0 mIU/L, regardless of the TPO Ab status, had a 2.01-fold increased risk of LBW. Subclinical hypothyroidism, regardless of the TPO Ab status, was associated with a 1.94-fold higher risk of LBW when compared with that in subjects with euthyroidism and TPO Ab-. No other significant associations were observed. Conclusion: A maternal TSH concentration of 2.5-4.0 mIU/L was associated with a lower risk of LBW when combined with TPO Ab-, whereas subjects with a TSH concentration of >4.0 mIU/L had an increased risk of LBW. Subclinical hypothyroidism appears to be associated with a higher risk of LBW.

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.

[Prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong province].

OBJECTIVE: To investigate the prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong province. METHODS: Data from 169 218 pregnant women in different regions of Guangdong province from January 2005 to June 2010 were analyzed retrospectively. The prevalence and epidemiological characteristics of thromboembolic disease during pregnancy or puerperium were investigated. RESULTS: Of the studied population, (1) 201 cases (1.3‰) suffered from thromboembolic disease during pregnancy or puerperium including 128 cases of deep vein thrombosis (DVT), 68 cases of cerebral venous thrombosis (CVT) and 5 pulmonary embolism, the prevalence rates were 0.8‰, 0.4‰, and 0.02‰ respectively. (2) Risk factors in different regions showed that, in the Pearl River Delta area, the major risk factors for DVT would include previous or family history of thrombosis, pregnancy complications, with medically involved diseases, prolonged bed rest and pregnancy weight gain>15 kg etc. While in eastern, western, northern parts of Guangdong, the major risk factors for DVT would include pregnancy weight gain>15 kg, prolonged bed rest, preeclampsia, cesarean section and complications during pregnancy. In Pearl River Delta region, the major risk factors for CVT would include eclampsia, preeclampsia, pregnancy complications, prolonged bed rest>3 days, past history or family history of thrombosis. While eclampsia, preeclampsia, advanced age or younger age, pregnancy weight gain>15 kg, complications during pregnancy were the major risk factors for CVT in the eastern, western or northern parts of Guangdong. CONCLUSION: Prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong were different. It was crucial to take effective measures in pregnant women with different epidemiological characteristics and risk factors to prevent and reduce the incidence of peripartum thromboembolic disease.

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.