Low-molecular-weight heparin for the prevention of preeclampsia in high-risk pregnancies without thrombophilia: a systematic review and meta-analysis.

OBJECTIVES: To systematically evaluate the efficacy of low molecular weight heparin (LMWH) to prevent preeclampsia in high risk pregnant women without thrombophilia. SEARCH STRATEGY: PubMed, Embase and the Cochrane library were searched for articles published before 1st August 2022 using the combination keywords "preeclampsia", "Low Molecular Weight Heparin", "LMWH", "Heparin, Low Molecular Weight", "Dalteparin", "Nadroparin", and "Tinzaparin". SELECTION CRITERIA: Randomized controlled trials evaluating the use of LMWH in pregnant women at high risk of preeclampsia without thrombophilia. DATA COLLECTION AND ANALYSIS: Ten studies were included in the meta-analysis (1758 patients in total). Outcomes were expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS: LMWH reduced the incidence of PE (RR = 0.67; 95% CI = 0.50-0.90; P = 0.009) in high risk pregnant women without thrombophilia. Subgroup analysis found that the prophylactic effect of LMWH was only significant in studies using low-dose aspirin (LDA) as the primary intervention. The combination of LMWH and LDA was also effective for the prevention of preterm birth and fetal growth restriction, but had no effect on the incidence of placenta abruption. CONCLUSION: For women at high risk of developing preeclampsia without thrombophilia, the combination of LMWH and low-dose aspirin is effective for the prevention of preeclampsia, preterm birth and fetal growth restriction and is superior to LDA alone.

Transversus Thoracic Muscle Plane Block For Postoperative Pain in Pediatric Cardiac Surgery: A Systematic Review And Meta-Analysis of Randomized And Observational Studies.

OBJECTIVES: Pediatric patients undergoing cardiac surgery usually experience significant surgical pain. Additionally, the effect of poor surgical analgesia creates a pain continuum that extends to the postoperative period. Transversus thoracic muscle plane block (TTMPB) is a novel plane block technique that can provide analgesia to the anterior chest wall. The analgesic role of TTMPB in pediatric cardiac surgery is still uncertain. A meta-analysis was conducted to determine the analgesic efficacy of this procedure. DESIGN AND SETTING: Systematic review and meta-analysis. PubMed, Embase, Web of Science, CENTRAL, WanFang Data, and the China National Knowledge Infrastructure were searched to November 2023, and the Grading of Recommendations Assessment, Development, and Evaluation approach was followed to evaluate the certainty of evidence. PARTICIPANTS: Eligible studies enrolled pediatric patients from 2 months to 12 years old scheduled to undergo cardiac surgery, and randomized them to receive a TTMPB or no block/sham block. MEASUREMENTS AND MAIN RESULTS: Six studies that enrolled 601 pediatric patients were included. Low-certainty evidence from randomized trials showed that, compared with no block or sham block, TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative modified objective pain score at 12 hours (weighted mean difference [WMD] -2.20, 95% CI -2.73 to -1.68) and 24 hours (WMD -1.76, 95% CI -2.09 to -1.42), intraoperative opioid consumption (WMD -3.83, 95% CI -5.90 to -1.76 µg/kg), postoperative opioid consumption (WMD -2.51, 95% CI -2.84 to -2.18 µg/kg), length of intensive care unit (ICU) stay (WMD -5.56, 95% CI -8.30 to -2.83 hours), and extubation time (WMD -2.13, 95% CI -4.21 to -0.05 hours). Retrospective studies provided very low certainty that the results were consistent with the randomized trials. CONCLUSION: Very low- to low-certainty evidence showed that TTMPB in pediatric patients undergoing cardiac surgery may reduce postoperative pain, opioid consumption, ICU length of stay, and extubation time.

Effect of Nutritional Intervention on Energy Intake in Head and Neck Cancer Patients After Radiotherapy.

Objective: This study aimed to analyze the impact of nutritional intervention during radiotherapy for head and neck tumors and its effects on energy intake, consumption, and nutritional status. Methods: A comparative or observational study was conducted, and a total of 103 head and neck tumor patients undergoing radiotherapy were selected for this study and divided into two groups. The control group (n = 51) received routine nursing intervention, while the observation group (n = 52) received additional nutritional intervention. We compared the nutritional status, energy intake and consumption, and emotional well-being between the two groups. Results: After the intervention, the observation group exhibited significantly higher levels of BMI, serum prealbumin, hemoglobin, and albumin compared to the control group (P < .05). Energy intake during radiotherapy was significantly higher in the observation group than in the control group. Furthermore, the energy consumption in the observation group was significantly lower than in the control group (P < .05). After the intervention, the observation group reported lower scores on the Self-rating Anxiety Scale and Self-rating Depression Scale compared to the control group (P < .05). In a three-month follow-up after radiotherapy, the observation group's EORTC Cancer Quality of Life Scale score was also significantly higher than that of the control group (P < .05). Conclusions: Nutritional intervention proved effective in increasing energy intake and reducing energy consumption in patients undergoing radiotherapy for head and neck tumors. This improvement positively impacted the nutritional status and quality of life of the patients, emphasizing its significant research value.

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.

BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.

Hyperglycemia in Pregnancy-Associated Oxidative Stress Augments Altered Placental Glucose Transporter 1 Trafficking via AMPKα/p38MAPK Signaling Cascade.

GLUT1, being a ubiquitous transporter isoform, is considered primarily responsible for glucose uptake during glycolysis. However, there is still uncertainty about the regulatory mechanisms of GLUT1 in hyperglycemia in pregnancy (HIP, PGDM, and GDM) accompanied by abnormal oxidative stress responses. In the present study, it was observed that the glycolysis was enhanced in GDM and PGDM pregnancies. In line with this, the antioxidant system was disturbed and GLUT1 expression was increased due to diabetes impairment in both placental tissues and in vitro BeWo cells. GLUT1 responded to high glucose stimulation through p38MAPK in an AMPKα-dependent manner. Both the medical-mediated and genetic depletion of p38MAPK in BeWo cells could suppress GLUT1 expression and OS-induced proapoptotic effects. Furthermore, blocking AMPKα with an inhibitor or siRNA strategy promoted p38MAPK, GLUT1, and proapoptotic molecules expression and vice versa. In general, a new GLUT1 regulation pathway was identified, which could exert effects on placental transport function through the AMPKα-p38MAPK pathway. AMPKα may be a therapeutic target in HIP for alleviating diabetes insults.

Exosomal miRNAs as Biomarkers of Cancer: a Meta-Analysis.

BACKGROUND: Tumor-derived exosomal miRNAs secreted by cancer cells play significant roles in the pathological processes of cancer, but no systematic meta-analysis has focused on the diagnostic efficiency of exosomal miRNAs. This meta-analysis assessed the diagnostic value of circulating exosomal miRNA in cancer. METHODS: Studies evaluating the diagnostic value of exosomal miRNA were identified in EMBASE, PubMed, Cochrane Library, and Web of Science up to August 1, 2018. The quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2, and STATA 14.0 was used for the analyses. The true positive (TP), false positive (FP), true negative (TN), and false negative (FN) rates were extracted from each study to obtain the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (CIs). RESULTS: The meta-analysis included 16 studies with 1,591 patients. Five studies reported sensitivity values, and the pooled sensitivity was 0.86 (95% CI = 0.80 - 0.90, while 29 studies reported specificity values, and the pooled specificity was 0.89 (95% CI = 0.83 - 0.93). The pooled PLR was 7.8 (95% CI = 4.9 - 12.4), the pooled NLR was 0.16 (95% CI = 0.11 - 0.24), the pooled DOR was 48 (95% CI = 23 - 101), and the AUC was 0.94 (0.91 - 0.96). CONCLUSIONS: Our meta-analysis indicated that body fluid exosomal miRNAs are highly accurate for distinguishing patients from healthy individuals, and exosomal miRNAs have superior diagnostic value in plasma, prostate cancer patients, and non-Asian individuals.

Overexpression of IGF2 affects mouse weight and glycolipid metabolism and IGF2 is positively related to macrosomia.

Objective: To investigate the effects of insulin-like growth factor 2 (IGF2) on growth and glycolipid metabolism, as well as the underlying mechanism. Methods: A mouse model of IGF2 overexpression was constructed to measure weight gain before adulthood, to obtain the values of adult glycolipid metabolism indicators in the peripheral blood and to detect the expression of genes in the IGF2 signaling pathway in different mouse tissues. The present study also explored the independent association between the IGF2 gene and macrosomia by detecting and comparing the expression levels of IGF2 mRNA/H19 RNA in maternal peripheral blood and fetal cord blood of 26 human pregnancies. Results: In the mouse model, weights of the IGF2-overexpressing mice were significantly higher than those of the control mice at the age of 5-10 weeks. The glucose concentration, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels of IGF2-overexpressing mice were significantly lower than those of wild-type (WT) mice. Compared with the WT mice, the expression of H19 was significantly decreased in the pancreas and IGF1R was significantly decreased in the muscle of mice with IGF2 overexpression. The expression levels of STAT3 and AKT2 showed significant decrease in liver, muscle and increase in muscle of IGF2-overexpressing mice, respectively. GLUT2 expression showed significant increase in liver, kidney, muscle and decrease in pancreas of mice with IGF2 overexpression. This study also found that in normal mothers with the similar clinical characteristics, IGF2 expression in the maternal peripheral blood and fetal cord blood is an independent factor influencing macrosomia. Conclusion: IGF2 expression was independently correlated with the occurrence of macrosomia, and overexpression of IGF2 significantly increased the weights of mice at the age of 5-10 weeks and significantly affected the values of adult glycolipid metabolism indicators, which might be the result of changes in the IGF2-IGF1R-STAT3/AKT2-GLUT2/GLUT4 pathway. These findings might suggest that IGF2 plays an important role in growth and glycolipid metabolism during both pregnancy and postnatal development.

Low-dose aspirin in the prevention of pre-eclampsia in China: postpartum hemorrhage in subgroups of women according to their characteristics and potential bleeding risk.

BACKGROUND: The APPEC study is a large-population randomized controlled trial in China evaluating the role of low-dose aspirin prophylactic treatment for pre-eclampsia. There was no statistically significant difference in postpartum hemorrhage (PPH) incidence between the aspirin and control groups. This study aimed to evaluate the potential bleeding risk of 100 mg aspirin in high-risk pregnant women and the difference in the incidence of PPH according to maternal characteristics. METHODS: This is a secondary data analysis of the APPEC study. Platelet counts and coagulation test results were collected at five follow-up visits. Subgroups defined by maternal age (<35 years and ≥35 years), pre-pregnancy body mass index (pre-BMI, <28 kg/m 2 and ≥28 kg/m 2 ), parity, gestational age at enrollment, and medical history, including pre-eclampsia, chronic hypertension, and diabetes mellitus, were analyzed. Logistic regression analysis was used to determine the statistical significance of the difference in the incidence of PPH after aspirin administration in pregnant women in each subgroup. Adjustment using multiple logistic regression models followed these analyses. Binary logistic regression was used to determine the relationship between pre-BMI and PPH. RESULTS: There was no significant difference between the aspirin and control groups in bleeding risk (3.4% [16/464] vs. 3.0% [13/434], T = 0.147, P  = 0.701). No significant difference was found in the incidence of PPH in total (relative risk  = 1.220, 95% confidence interval [CI] = 0.720-2.067, P  = 0.459; aspirin group vs. control group, 6.5% [30/464] vs. 5.3% [23/434], P  = 0.459) or in subgroup analysis. A significant correlation between pre-BMI and PPH was found in the aspirin group, while in the control group there was no significant correlation (aspirin group, odds ratio [OR] = 1.086, 95% CI = 1.004-1.175, P  = 0.040; control group, OR = 1.060, 95% CI = 0.968-1.161, P  = 0.209). CONCLUSIONS: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not increase the risk of potential bleeding and PPH regardless of the maternal characteristic. In the aspirin group, the positive correlation between BMI and PPH was significant. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01979627.

METTL3 regulates glucose transporter expression in placenta exposed to hyperglycemia through the mTOR signaling pathway.

BACKGROUND: Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP. METHODS: We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. RESULTS: mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. CONCLUSION: High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Ultrasound-guided lateral pterygoid muscle botulinum toxin: an injection for recurrent temporomandibular joint dislocation in a brain injury patient.

Botulinum toxin type A (BTX-A) injection using nerve stimulation or electromyography for recurrent temporomandibular joint (TMJ) dislocation has been reported for several years. However, using the available equipment like a nerve stimulator or an electromyograph is uncommon, and ultrasound guidance is convenient and requires no additional resources. In this report, we used ultrasound as a tool to achieve BTX-A injections in a patient with a traumatic brain injury to treat her TMJ dislocation. One week after the injections, she had no more dislocation. She remained symptom free during the 3 months of follow-up, and her clinical symptoms improved without significant complications. This is the first report using ultrasound guidance for BTX-A injections to treat recurrent TMJ dislocation. This treatment is an effective and safe technique that could be performed timely and locally without referral to a center with electromyography facilities.

[Effects of transcutaneous electrical acupoint stimulation at different times assisted general anesthesia on stress response of patients undergoing open posterior lumbar surgery].

OBJECTIVE: To observe the effects of transcutaneous electrical acupoint stimulation (TEAS) at different times on the stress response during anesthesia and operation in the patients undergoing open posterior lumbar surgery. METHODS: A total of 94 patients undergoing open posterior lumbar surgery were randomly assigned to preoperative TEAS group(32 cases), intraoperative TEAS group(31 cases) and sham-TEAS group(31 cases). The same anesthetic method was used in the patients of 3 groups. Four electrodes were attached to the bilateral Hegu (LI4) and Neiguan (PC6) and connected to the electronic acupuncture instrument when patients entered the operation room. In the preoperative TEAS group, the patients received TEAS (10 to 20 mA) for 30 min before the anesthetic induction. TEAS (15 mA) was provided immediately when the operation starts till the end of ope-ration for the patients of the intraoperative TEAS group. In the sham-TEAS group, the electronic acupuncture instrument was switched on during the whole procedure of operation, but no electric current was output. Separately, at the moment of entering the operation room (T0), before endotracheal intubation (T1), at the time of endotracheal intubation (T2), 10 min after skin resection (T3), at the end of surgery (T4), recovery from anesthesia (T5) and at the time of extubation (T6), the heart rate (HR) and mean arterial pressure (MAP) were recorded. Using ELISA, the concentrations of epinephrine (E), norepinephrine (NE), dopamine (DA), cortisol (Cor) in serum were assayed at T0, T3, and T4; and blood glucose was tested with blood sugar paper at the same time points. RESULTS: Compared with T0 of the same group, HR was increased at T2 and decreased at T3 of the patients in the sham-TEAS group and the intraoperative TEAS group (P<0.05). Compared with the sham-TEAS group at the same time points, HR was decreased at T2 and increased at T3 of the patients in the preoperative TEAS group (P<0.05), and it was decreased at T6 of patients in the intraoperation TEAS group (P<0.05). HR was reduced at T2 in the preoperative TEAS group when compared with the intraoperative TEAS group. Compared with T0 of the same group, MAP was elevated at T2 and reduced at T3 and T4 in the sham-TEAS group (P<0.05); it decreased at T3, T4 and T5 in the preoperative TEAS group (P<0.05); it rose at T2 and was reduced at T3, T4 and T5 in the intraoperative TEAS group (P<0.05). When compared with the sham-TEAS group at the same time points, MAP decreased at T2 in the preoperative TEAS group (P<0.05), and at T6 in the intraoperative TEAS group (P<0.05). MAP was reduced at T2 and elevated at T6 in the preoperative TEAS group in comparison with the intraoperative TEAS group (P<0.05) at the same time points. Compared with T0 of the same group, the contents of E was increased at T3 in the sham-TEAS group and the intraoperative TEAS group (P<0.05); it was increased in all of the three groups at T4 (P<0.05); the contents of NE, DA, Cor and the blood glucose were increased at T4 in the sham-TEAS group (P<0.05). Compared with the sham-TEAS group at the same time points, the contents of E, DA at T3 and T4 and Cor at T3 in serum of the preoperative TEAS group were decreased (P<0.05); and the contents of E, NE, DA and Cor at T4 in the intraoperative TEAS group were decreased (P<0.05). CONCLUSION: TEAS-assisted general anesthesia can better maintain the stability of HR and MAP during anesthesia and operation in patients undergoing open posterior lumbar surgery, and reduce surgical stress response.

Enhancing denitrification in constructed wetland with algae addition.

Constructed wetlands (CWs) can be used for tertiary treatment of wastewater; however, carbon source shortages limit denitrification. We studied the effect of algae addition as an external carbon source in CWs and found that the nitrogen removal efficiency of CWs is highly dependent on the algae dosage. Optimal nitrogen removal percentage (80.5%) can be achieved by adding 81.1 mg·L-1 dry weight algae to the influent when the chemical oxygen demand/nitrogen (COD/N) ratio reaches 5.3. Longitudinal changes in the nitrogen concentrations, organic matter concentrations, and nitrogen functional genes were also analyzed. The algae addition strengthened the anoxic environment, boosted the volatile fatty acid concentrations, and improved the ratio of nitrite reductase gene (nirS) and copper-containing nitrite reductase (nirK)/16S rRNA, as well as the ratio of nitrate reductase gene (narG)/16S rRNA, thereby expanding the active space for denitrification. The addition of algae could potentially provide enough carbon to enhance denitrification during treatment of wastewater with a low COD/N ratio.

Gut microbiota in women with gestational diabetes mellitus has potential impact on metabolism in pregnant mice and their offspring.

Studies have shown that gestational diabetes mellitus (GDM) is closely related to abnormalities in the gut microbiota, and the offspring of these women have an increased risk of diabetes. There is no direct evidence of whether bacteria in women with GDM colonize the intestinal tract of offspring and cause hyperglycemia. In this fecal microbiota transplantation (FMT), pregnant mouse model study, two groups of germ-free (GF) mice after FMT showed different colonization patterns of gut microbiota and phenotype. Compared with the control group (healthy-FMT), we found in the GDM-FMT group as a lower relative abundance of Akkermansia and Faecalibacterium; a lower content of short-chain fatty acids and naringenin in feces; an elevated blood glucose; an inflammatory factor expression (TNF-α, CXCL-15, and IL-6), and a hepatic fat deposition. In addition, the influence of the gut microbiota continued in offspring. The gut microbiota of the offspring of GDM-FMT mice was still different from that of the control group as a lower relative abundance of Akkermansia and Parvibacter; and a higher relative abundance of bacteria such as Oscillibacter, Romboutsia, and Harryflintia. In addition, the offspring of GDM-FMT mice had higher body weight and blood glucose levels than the control offspring.

Irisin participates in the beneficial effects of exercise in preventing gestational diabetes mellitus in overweight and obese pregnant women and a mouse model.

Objective: We aimed to explore whether irisin participates in the beneficial effects of exercise in preventing gestational diabetes mellitus (GDM) in overweight and obese pregnant women. Study design: Sixty overweight and obese pregnant women each in the exercise and control groups were randomly selected from our previous randomized controlled trial. Eighteen obese model mice were generated and divided into exercise and control groups in which body weight, abdominal circumference, anal temperature, glucose tolerance test, and insulin tolerance test were recorded. The plasma irisin level, the expression of PGC-1α/FNDC5 and brown (UCP1) and beige adipose (CD137, TMEM26, and TBX-1) marker genes were detected in muscle and adipose tissue. Results: In the human study, women in the exercise group had a significantly higher irisin level and lower insulin resistance level than those in the control group. Enhanced expression of beige adipose tissue marker genes (CD137, TMEM26, and TBX-1) in omental adipose tissue and the CD137 gene in subcutaneous adipose tissue were found in the exercise group compared to the control group. In a mouse model, body weight and abdominal circumference were decreased, while glucose homeostasis and insulin sensitivity were significantly improved, and anal temperature was elevated after exercise intervention. A significantly higher level of irisin was revealed in the exercise group after undergoing exercise treatment. The expression of the beige adipose marker genes CD137 and TBX-1 was significantly higher in the exercise group than in the control group in posterior subcutaneous adipose tissue from the inguinal area and interscapular adipose tissue respectively. Conclusion: Our observations show that regular exercise during pregnancy can increase irisin levels, promote white fat beiging/browning, improve glucose homeostasis and enhance body energy expenditure, which may be one of the mechanisms by which exercise prevents GDM.

Preventive effect of aspirin on preeclampsia in high-risk pregnant women with stage 1 hypertension.

Studies reported that women in a low-risk cohort with stage 1 hypertension defined as 130-139 mmHg/80-89 mmHg, according to the American College of Cardiology/American Heart Association, are more likely to develop into preeclampsia than women with normotensive in the early gestation. In this study, the authors investigated whether preeclampsia was more likely to occur in stage 1 hypertensive women compared to the normotensive pregnant women in a high-risk cohort, which was based on the randomized controlled trial of "Low-dose Aspirin in the Prevention of Preeclampsia in China." Meanwhile, the authors further evaluated the preventive effect of aspirin for preeclampsia in stage 1 hypertension subset. In women enrolled at or before 16 weeks of gestation, in the control group, the preeclampsia occurrence was significantly higher in stage 1 hypertensive woman than in the normotensive women (20.4% vs. 6.2%, aOR 3.960, 95% CI 1.299-12.074, p = .016), while no difference was observed in the aspirin group (4.5% vs. 4.2%, aOR 0.921, 95% CI 0.140-6.070, p = .932). In stage 1 hypertension, the incidences of preeclampsia and preterm birth were significantly lower in the aspirin group as compared to the control group (4.5% vs. 20.4%, aOR 0.139, 95% CI 0.027-0.716, p = .018; 4.5% vs. 18.4%, aOR 0.141, 95% CI 0.025-0.782, p = .025). Compared with the control group, the aspirin group displayed significantly prolonged gestational age at delivery (38.6 ± 1.2 vs. 37.4 ± 3.4, p = .042). This study indicates that the newly classified stage 1 hypertension might be an additional risk factor for preeclampsia in Chinese high-risk pregnant women, and aspirin intervention might be useful.

Phosphoproteomics reveals the apoptotic regulation of aspirin in the placenta of preeclampsia-like mice.

Preeclampsia (PE) is a severe gestational complication, and dysfunctional placenta plays an essential role in PE pathogenesis. Although low-dose aspirin is currently the most promising prophylactic drug for PE prevention, the exact mechanism of aspirin remains unclear. A previous study reported that treatment with low-dose aspirin could ameliorate PE-like symptoms in lipopolysaccharide (LPS)-induced PE-like mouse model. This study aimed to uncover the potential mechanism of aspirin action in PE through quantitative phosphoproteomics comparison. We established the following four groups: a control (CTRL) group, an LPS-treated (L) group, an LPS + aspirin co-treatment (LA) group, and an aspirin-treated (A) group. A total of 4350 phosphosites and 4170 phosphopeptides from 1866 phosphoproteins were identified in the placenta on embryonic day 13.5. Among the significantly altered phosphoproteins identified, apoptosis-related pathways were significantly regulated in both the L group vs. CTRL group and the LA group vs. L group comparisons. We demonstrated that apoptosis was increased in the placenta of PE-like mice and was inhibited in the LA group by quantify the apoptosis-positive cells and the protein levels of cleaved caspase 3, 8, and 9. Moreover, the phosphorylation of HSP90ß (S254) and GSK3ß (Y216) may be a crucial factor in the aspirin-mediated regulation of apoptosis according to protein-protein interaction analysis. This study revealed that apoptosis regulation is a mechanism of aspirin action in PE, particularly in women with over-activated inflammation. The phosphorylation of HSP90ß (S254) and GSK3ß (Y216) could be the key intervention targets.

Protective effect of rhodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury.

Rhodioloside has been shown to protect cells from hypoxia injury, and bone marrow mesenchymal stem cells have a good effect on tissue repair. To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury, a rat model of spinal cord injury was established using the Infinite Horizons method. After establishing the model, the rats were randomly divided into five groups. Rats in the control group were intragastrically injected with phosphate buffered saline (PBS) (5 µL). PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm. Rats in the rhodioloside group were intragastrically injected with rhodioloside (5 g/kg) and intramuscularly injected with PBS. Rats in the mesenchymal stem cell (MSC) group were intramuscularly injected with PBS and intramuscularly with MSCs (8 × 106/mL in a 50-µL cell suspension). Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs. Rats in the rhodioloside + Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside. One week after treatment, exercise recovery was evaluated with a modified combined behavioral score scale. Hematoxylin-eosin staining and Pischingert's methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue. Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord. Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord. The results showed that: (1) compared with the other groups, the rhodioloside + Ad-HIF-MSC group exhibited the highest combined behavioral score (P < 0.05), the most recovered tissue, and the greatest number of neurons, as indicated by Pischingert's methylene blue staining. (2) Compared with the PBS group, HIF-1 protein expression was greater in the rhodioloside group (P < 0.05). (3) Compared with the Ad-HIF-MSC group, Sry mRNA levels were higher in the rhodioloside + Ad-HIF-MSC group (P < 0.05). These results confirm that rhodioloside combined with bone marrow mesenchymal stem cells can promote the recovery of spinal cord injury and activate the HIF-1 pathway to promote the survival of bone marrow mesenchymal stem cells and repair damaged neurons within spinal cord tissue. This experiment was approved by the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine, China (approval No. 2015KYLL029) in June 2015.

Role of mammalian target of rapamycin signaling pathway in regulation of fatty acid oxidation in a preeclampsia-like mouse model treated with pravastatin.

BACKGROUND: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several studies show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nω-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra. METHODS: Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n = 8) or normal saline (NS; L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA). RESULTS: Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74 ±â€Š0.08 vs. 0.85 ±â€Š0.06, t = 2.95, P < 0.05; placenta: 0.63 ±â€Š0.06 vs. 0.77 ±â€Š0.06, t = 4.64, P < 0.05). The activation of mTOR protein in the liver and placenta negatively correlated with the expression of LCHAD in the L-NAME + NS group (liver: r = -0.745, P < 0.05; placenta: r = -0.833, P < 0.05) and that in the maternal liver negatively correlated with the expression of LCHAD (r = -0.733, P < 0.05) and positively with the serum FFA levels (r = 0.841, P < 0.05) in the L-NAME + Pra group. CONCLUSION: The inhibition of mTOR signaling pathway might be involved in the regulation of FAO in mouse model treated with Pra.

A meta-analysis of the effects of probiotics and synbiotics in children with acute diarrhea.

OBJECTIVE: This meta-analysis assessed the effectiveness of probiotics and synbiotics for acute diarrhea (AD) in children and investigated probiotic formulations, types of interventions, and country factors. METHODS: Randomized, double-blind, placebo-controlled trials evaluating the effects of probiotics or synbiotics on AD were analyzed. We followed the recommendations of the Cochrane Handbook and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risks of systematic errors (bias) and random errors were assessed, and the overall quality of the evidence was evaluated using the Grades of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: The meta-analysis included 34 studies with 4911 patients. Five and 29 studies presented the results of synbiotic and probiotic interventions, respectively. After intervention, the durations of diarrhea (weighted mean difference (WMD) = -16.63 [-20.16; -12.51]) and hospitalization (risk ratio (RR) = 0.59 [0.48; 0.73]) were shorter, the stool frequency on day 3 (WMD = -0.98 [-1.55; -0.40]) was decreased, and the incidence of diarrhea lasting 3 days was lower in the probiotic and synbiotic groups than in the control groups. Furthermore, in the subgroup analyses, synbiotics were more effective than probiotics at reducing the durations of diarrhea and hospitalization, and Saccharomyces and Bifidobacterium were more effective than Lactobacillus at reducing the duration of diarrhea. CONCLUSION: This meta-analysis supports the potential beneficial roles of probiotics and synbiotics for AD in children. Further research is needed to determine problems associated with probiotic/synbiotic mixtures and appropriate dosages.