Down-Regulation of MicroRNA-214 Contributed to the Enhanced Mitochondrial Transcription Factor A and Inhibited Proliferation of Colorectal Cancer Cells.

BACKGROUND/AIMS: Colon cancer, also known as colorectal cancer (CRC), is one of the most common malignant tumors globally. Although significant advances have been made for developing novel therapeutics, the mechanisms of progression of colorectal cancer are still poorly understood. METHODS: In this study, we identified down-regulation of microRNA-214 (miR-214) as the contributing factor for CRC. Mitochondrial transcription factor A (TFAM) and miR-214 expression in tumor samples from colorectal cancer patients and cancer cell lines were examined by reverse transcription and real-Time PCR (qPCR) or Western Blotting. RESULTS: Our data demonstrated that miR-214 was significantly down-regulated in the tissue samples from CRC patients as well as CRC derived cell lines. TFAM overexpression was also observed in CRC patients and identified as a target for miR-214. Knockdown of TFAM by miR-214 mimics significantly inhibited the proliferation of CRC cell lines. Also, down-regulation of TFAM inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation and the expression of NF-κB depended genes. CONCLUSION: In conclusion, our data suggested that down-regulation of MiR-214 contributed to the enhanced TFAM expression and decreased proliferation of CRC cells.

Role of foetal umbilical artery Doppler on prediction of adverse pregnancy outcomes in patients with systemic lupus erythematosus.

OBJECTIVES: To investigate the foetal outcomes and examine the predictive value of the third-trimester umbilical artery Doppler in systemic lupus erythematosus (SLE) pregnancies. METHODS: Data of 180 pregnancies in 175 SLE patients from Jan 2007 to Jan 2017 were analysed retrospectively. Pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) of the umbilical artery flow velocity data were monitored by Doppler ultrasound. RESULTS: One or more composite adverse pregnancy outcomes (APOs) occurred in 46.7% of patients with SLE. A total of 62 (34.4%) pregnancies were pre-term birth, and 34 (18.9%) newborns were small for gestational age (SGA). Twenty-two of pregnancies (12.2%) resulted in foetal distress. In multivariate analysis, predictors of composite APOs included positive anti-Ro (OR 5.5, 95% CI 1.7-18.2, p=0.005) and low complement (OR 3.9, 95% CI 1.1-13.6, p=0.04). Doppler PI, RI, and S/D were significantly higher in the pre-term birth, SGA, and composite APO groups than in the patients without APOs. RI with cut-off values of 0.57 and 0.70 indicated the highest risk of pre-term birth and composite APOs, with sensitivities of 50.0% and 21.4%, as well as specificities of 59.6% and 97.7%, respectively. PI emerged as the best predictor of SGA. The optimal cutoff value for PI was 0.77, at which sensitivity (90.9%) and specificity (49.2%) had the best combination. CONCLUSIONS: Pregnancies in lupus still had an increased risk of APOs in terms of pre-term birth. Third-trimester umbilical artery Doppler was useful in predicting pre-term birth, SGA, and composite APOs in lupus pregnancies.

[Assessment of ovarian reserve with anti-Müllerian hormone in female patients with systemic lupus erythematosus].

OBJECTIVE: To evaluate the serum level of anti-Müllerian hormone (AMH) in female patients with systemic lupus erythematosus (SLE) and identify its correlations with age and cyclophosphamide (CYC) therapy. METHODS: A total of 77 SLE female patients and 38 control healthy women with regular menstrual cycles were recruited. AMH was measured by enzyme linked immunosorbent assay (ELISA) kit. Follicle-stimulating hormone (FSH), estradiol (E2) and antral follicle count (AFC) of bilateral ovary were detected at the third day of menstrual cycle. RESULTS: Their mean age was (29 ± 5) years (range, 20-40) and the mean duration (2.7 ± 2.4) years. The mean serum level of AMH was (1.5 ± 1.3) µg/L and AFC 10 ± 7. Linear regression revealed AFC (r = 0.9, P < 0.01) was associated with the level of AMH. The mean levels of AMH and AFC were significantly higher in patients naїve to CYC therapy than in those under exposure, but lower than that in healthy control (P < 0.01). No difference existed in FSH and E2 among 3 groups. Compared with those above 30 years old, the patients aged 30 years and younger had significantly higher level of AMH (P < 0.01). The Spearman's correlation analysis indicated that each 5 gm of CYC exposure were independently associated with a lower level of AMH (r = -0.4, P < 0.01). CONCLUSION: As a more sensitive marker of ovarian reserve, AMH is associated with age and the cumulative dose of CYC. SLE patients aged >30 years and under exposure to CYC >10 g should be closely monitored for potential adverse events.

Pregnancy outcomes in patients receiving assisted reproductive therapy with systemic lupus erythematosus: a multi-center retrospective study.

OBJECTIVES: To evaluate the safety, efficacy, and maternal and fetal outcomes of assisted reproductive therapy (ART) in systemic lupus erythematosus (SLE). METHODS: Patients from three tertiary hospitals from Guangzhou, China followed-up from 2013 to 2022 were included retrospectively. Patients with planned or unplanned natural pregnancy were chosen as controls. ART procedure and pregnancy outcomes were recorded and compared. RESULTS: A total of 322 ART cycles in 142 women were analyzed. Sixty-six intrauterine pregnancies out of 72 clinical pregnancies yielded 65 live infants, including 5 pairs of twins. The clinical pregnancy rate was 46.5% (66/142). The mean age at the first clinical pregnancy was 34.0 ± 3.8 years. The median (interquartile range, IQR) disease course was 42.5 (25, 84.8) months. Twenty-seven (40.9%) of them had a history of adverse pregnancy. Primary infertility occurred in 20 (30.3%) patients. Obstruction of fallopian tubes (17/66, 25.8%) and premature ovarian failure (9/66, 13.6%) were the leading causes for infertility. Ovulation induction therapy (OIT) were conducted in 60 (83.3%) pregnancies, and no ovarian hyperstimulation syndrome (OHSS) or thrombosis was observed. The leading maternal adverse pregnancy outcomes (APOs) included premature delivery (21/66, 31.8%), gestational diabetes mellitus (GDM) (15/66, 22.7%), and disease flares (10/66, 15.2%). Spontaneous premature delivery (9/21, 42.9%) and preterm premature rupture of membranes (PPROM) (6/21, 28.6%) were the leading causes for premature delivery. Preeclampsia (19.0% vs 0%, P = 0.012) increased in premature delivery. Infants delivered prematurely were likely to be low-birth-weight (LBW)/very-low-birth-weight (VLBW) (81.0% vs 7.7%, P < 0.001). Disease flares were mild (4/10, 40.0%) or moderate (5/10, 50.0%), and developed during the second (3/10, 30.0%) or third (6/10, 60.0%) trimester with favorable outcomes. Fetal loss in ART (6/66, 9.1%) was primarily attributed to early spontaneous abortion (n = 5). The average delivery time was 36.8 ± 2.1 weeks of gestation. The average birth weight was 2653.5 ± 578.6 g. LBW infants accounted for 30.8% (20/65). No neonatal death or neonatal lupus occurred. The incidence of adverse pregnancy outcomes did not increase in patients with ART compared with planned pregnancy and reduced significantly compared with an unplanned pregnancy. CONCLUSION: The safety and efficacy of ART is assured in lupus patients with stable disease. Maternal and fetal APOs are comparable with planned pregnancy, with a relatively high incidence of premature delivery, GDM, and LBW infants.

[Exploration on interaction of Chinese and Western drugs].

To study the interaction of traditional Chinese medicines and Western drugs in the interest of the interaction of Chinese and Western drugs viewing from their own characteristics, pharmacokinetics and pharmacodynamics to provide a scientific basis for rational clinical utilization of drugs. Pharmacological mutual coordination and/or restriction existed between the two kinds of drugs. When they were used in combination, it would increase or decrease adverse reactions, or even toxic reaction. When traditional Chinese drugs were used in combined with Western drugs, it is ought to know the nature and pharmacological effect of various chemical constituents in the compound for the best combination, try to avoid adverse drug interactions for the sake of reaching the goal of high effectiveness, safety and harmlessness.

Hypertensive disorders of pregnancy associated with adverse pregnant outcomes in patients with systemic lupus erythematosus: a multicenter retrospective study.

BACKGROUND: Hypertension disorders in pregnancy (HDP) were common complications in women with systemic lupus erythematosus (SLE). However, the impact of HDP and the measures to prevent HDP-related fetal adverse pregnancy outcomes (APOs) remained to be explored. METHODS: A multicenter retrospective study of 342 pregnant women with SLE was performed. Variables related to SLE and APOs were recorded. Fetal development was evaluated by umbilical artery Doppler ultrasonography. RESULTS: HDP was diagnosed in 45 (13.2%) patients, including pre-eclampsia in 42 and gestational hypertension in 3. Patients with HDP had higher incidence of preterm birth (71.1% vs 20.9%, P < 0.001), intrauterine growth retardation (IUGR) (37.8% vs 11.8%, P < 0.001), low-birth-weight infants (62.2% vs 17.2%, P < 0.001), and very-low-birth-weight infants (37.8% vs 2.7%, P < 0.001), compared with lupus patients without HDP. A total of 35 (77.8%) HDP patients had disease activation during pregnancy. All the events occurred during the second and third trimesters, mainly presenting as moderate-to-high activity (65.7%). Active disease [odds ratios (OR) = 3.9, 95% confidential interval (CI) 1.5-9.7, P = 0.004] and positive anticardiolipin (aCL) antibody (OR = 7.6, 95% CI 2.7-18.6, P < 0.001) were independent risk factors for HDP in lupus patients. Doppler RI and S/D ratio predicted APOs in patients with HDP. The optimal cut-off values for RI and S/D ratio were 0.7 (sensitivity 48.1%, specificity 53.3%) and 3.4 (sensitivity 66.7%, specificity 100%), respectively. CONCLUSIONS: HDP was a common pregnant complication and caused various fetal and maternal adverse outcomes in patients with SLE. Umbilical artery Doppler ultrasonography was effective in predicting fetal APOs in lupus patients with HDP.Key Points• HDP induced preterm birth, IUGR, low-birth-weight infants, and very-low-birth-weight infants in patients with SLE.• HDP led to lupus activation during the second and third trimesters.• Disease activation and aCL positivity were predictors for HDP.• RI and S/D ratio from umbilical artery Doppler predicted APOs in patients with HDP.

Beta-cell dysfunction is the primary contributor to the early postpartum diabetes among Chinese women with history of gestational diabetes mellitus.

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are at higher risk of future development of diabetes. This study investigated the risk factors associated with early postpartum abnormal glucose regulation (AGR) among Chinese women with a history of GDM. METHODS: A total of 186 women with a history of GDM were screened for early postpartum AGR at 6-8 weeks after delivery. Those with AGR were given lifestyle intervention therapy and reevaluated in 6-12 months. The demographic, anthropometric, prenatal and delivery data were recorded. The plasma high-sensitivity C-reactive protein (HsCRP) and lipid concentration were measured, and insulin secretion were analyzed. Insulinogenic index Deltains30'/DeltaBG30', the homeostasis model assessment index (HOMA)-B, and HOMA-IR were calculated. Multiple regression analysis was performed to identify the risk factors. RESULTS: Of the GDM women 28.0% (52/186) had AGR at 6-8 weeks after delivery; 45.2% (17/40) of these AGR women reminded abnormal after 6-12 month lifestyle intervention. Compared to the women who reverted to normal, women with consistent AGR showed significantly lower fasting insulin concentration, lower Deltains30'/DeltaBG30' as well as lower HOMA-B. No significant differences in age, body mass index (BMI), waist circumference, blood pressure, lipid level, HsCRP and HOMA-IR were observed between the two groups. Pre-pregnancy BMI = 25 kg/m(2), fasting glucose level = 5.6 mmol/L and/or 75 g oral glucose tolerance test (OGTT) 2 hours glucose level = 11.1 mmol/L during pregnancy were predictors for the AGR at 6-8 weeks after delivery. Deltains30'/DeltaBG30 = 1.05 was a significant risk contributor to the consistent early postpartum AGR. CONCLUSION: There is a high incidence of early postpartum AGR among Chinese woman with prior GDM. Beta-cell dysfunction, rather than insulin resistance or inflammation, is the predominant contributor to the early onset and consistent AGR after delivery.

Fetal and Maternal Outcomes of Planned Pregnancy in Patients with Systemic Lupus Erythematosus: A Retrospective Multicenter Study.

OBJECTIVE: To investigate the fetal and maternal outcomes as well as predictors of APOs in women with SLE who conceived when the disease was stable, the so-called "planned pregnancy." Methods. A retrospective multicenter study of 243 patients with SLE who underwent a planned pregnancy was performed. APOs in fetus and mothers were recorded. RESULTS: The average age at conception was 28.9 ± 3.9 years. Duration of SLE prior to pregnancy was 4.4 ± 4.3 years. Fetal APOs occurred in 86 (86/243, 35.4%) patients. Preterm births, intrauterine growth retardation (IUGR), fetal distress, and fetal loss accounted for 22.2%, 14.8%, 11.1%, and 4.9%, respectively. Forty-two preterm infants (42/54, 77.8%) were delivered after the 34th week of gestation. All the preterm infants were viable. Fifty-two patients (52/243, 21.4%) had disease flares, among which 45 cases (45/52, 86.5%) were mild, 6 (6/52, 11.5%) were moderate, and 1 (1/52, 1.9%) was severe. Disease flares were mainly presented as active lupus nephritis (41/52, 78.8%), thrombocytopenia (10/52, 19.2%), and skin/mucosa lesions (9/52, 17.3%). Pregnancy-induced hypertension (PIH) occurred in 29 patients, among which 3 were gestational hypertension and 26 were preeclampsia. Multiple analysis showed that disease flares (OR, 8.1; CI, 3.8-17.2) and anticardiolipin antibody positivity (OR, 7.4; CI, 2.5-21.8) were associated with composite fetal APOs. CONCLUSION: Planned pregnancy improved fetal and maternal outcomes, presenting as a lower rate of fetal loss, more favorable outcomes for preterm infants, and less severe disease flares during pregnancy.

Fetal outcomes and associated factors of adverse outcomes of pregnancy in southern Chinese women with systemic lupus erythematosus.

This study aims to investigate the fetal outcomes and associated factors of adverse pregnancy outcomes (APOs) in pregnant women with systemic lupus erythematosus (SLE). Clinical data from 251 SLE patients with 263 pregnancies from 2001 to 2015 were analyzed retrospectively. APOs occurred in 70.0% of pregnancies, in which pregnancy loss occurred in 28.5%; preterm delivery occurred in 21.3%; intrauterine growth retardation occurred in 12.2%; and fetal distress occurred in 8.0%. Over time, the rate of APOs decreased from 82.8% during 2001~2005 to 59.6% during 2011~2015. In multivariate analysis, predictors of APOs included positive antiphospholipid antibodies (OR 8.4, 95% CI 1.7~40.8, P = 0.008), lower complement (OR 3.6, 95% CI 1.3~9.9, P = 0.01), hypoalbuminemia (OR 3.2, 95% CI 1.2~8.3, P = 0.02), and hypertension (OR 14.6, 95% CI 1.5~141.6, P = 0.02). The use of antimalarial medications was associated with lower risk for APOs (OR 0.3, 95% CI 0.1~0.7, P = 0.01). In total, 109 patients underwent fetal umbilical artery Doppler in the third trimester. The The adjusted systole/diastole (S/D) ratio, pulsatility index (PI) and resistance index (RI) of SLE patients with APOs were higher than that of patients without APOs (2.9±0.9 vs. 2.4±0.5, P = 0.001). Lupus pregnancy was still at high risk of APOs in terms of pregnancy loss and preterm delivery. Umbilical artery Doppler was a good monitor method for APOs in the third trimester.