Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials.

OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

[Distribution characteristics of soil water and nutrients in pear orchard and their relationship with yields in loess hilly region]. / é»„åœŸä¸˜é™µåŒºé¦™æ¢¨å›­åœŸå£¤æ°´åˆ†ã€å »åˆ†åˆ†å¸ƒç‰¹å¾åŠå ¶ä¸Žäº§é‡çš„å ³ç³».

We analyzed soil water, nutrients, and yields in three different slope sites in the sloping farmland under Yuluxiang pear planted in the loess hilly region of Western Shanxi, across the growth periods and different soil depths. The results showed that: 1) The yield of pear was in the order of high slope site > middle slope site > low slope site. In high slope site, the yield was significantly correlated with soil water content (SWC), soil organic matter (SOM), available potassium (AK), with AK showing the most significant effect. The yield of pear in middle and low slope sites was significantly correlated with SWC, SOM, and total nitrogen (TN), with SWC having the most significant effect on yield. The contents of SWC, SOM, available phosphorus (AP) and TN in high slope site were higher than in middle and low slope sites, while AK was the highest in middle slope site. 2) Among different soil depths, soil nutrient contents were the highest within 0-20 cm soil layer, but the lowest within 20-40 cm soil layer. The SWC was significantly lower within 0-20 cm than the other soil layers and was the highest within 20-40 cm soil layer. 3) Among different growth periods, the contents of SOM, AP, and TN were the highest in flowering period, the SWC was the highest in fruiting period, and AK content was the highest in maturing period. It was suggested that in the future management of pear water and fertilizer in the region, more K fertilizer should be applied in the high slope sites in the flowering period, while N and P compound fertilizer should be applied in the fruiting period, to enhance irrigation in middle and low slope sites to decrease the limitation of water with 300 m3·hm-2. Our results could provide theoretical support and data refe-rence for planting precision irrigation and scientific fertilization of pear planted in loess hilly areas.

Overproduction of D-pantothenic acid via fermentation conditions optimization and isoleucine feeding from recombinant Escherichia coli W3110.

D-pantothenic acid (D-PA), as a crucial vitamin, is widely used in food, animal feed, cosmetics, and pharmaceutical industries. In our previous work, recombinant Escherichia coli W3110 for production of D-PA was constructed through metabolic pathway modification. In this study, to enhance D-PA production, statistical optimization techniques including Plackett-Burman (PB) design and Box-Behnken design (BBD) first were adopted to optimize the culture condition. The results showed that the glucose, ß-alanine and (NH4)2SO4 have the most significant effects on D-PA biosynthesis. The response surface model based on BBD predicted that the optimal concentration is glucose 56.0 g/L, ß-alanine 2.25 g/L and (NH4)2SO4 11.8 g/L, the D-PA titer increases from 3.2 g/L to 6.73 g/L shake flask fermentation. For the fed-batch fermentation in 5 L fermenter, the isoleucine feeding strategy greatly increased the titer and productivity of D-PA. As a result, titer (31.6 g/L) and productivity (13.2 g/L·d) of D-PA were achieved, they increased by 4.66 times and 2.65 times, respectively, compared with batch culture. At the same time, the accumulation of acetate reduced from 29.79 g/L to 8.55 g/L in the fed-batch fermentation. These results demonstrated that the optimization of medium composition and the cell growth rate are important to increase the concentration of D-PA for microbial fermentation. This work laid the foundation for further research on the application of D-PA microbial synthesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02773-0.

Neuroprotective effects of Ilexonin A following transient focal cerebral ischemia in rats.

Ilexonin A is a compound isolated from the root of a plant commonly used in traditional Chinese medicine. The aim of the present study was to investigate the possible protective mechanism of Ilexonin A in rats subjected to occlusion of the middle cerebral artery (MCAO). Transient focal cerebral ischemia was induced by 2 h of MCAO, followed by reperfusion. Ilexonin A at doses of 20, 40 and 80 mg/kg were administered via intraperitoneal injection immediately following ischemia/reperfusion. The expression levels of glial fibrillary acidic protein (GFAP), ionized calcium­binding adapter molecule­1 (Iba­1), vascular endothelial growth factor (VEGF), fetal liver kinase­1 (Flk­1) and Nestin were examined using immunostaining and Western blot analysis of the peri­infarct region following ischemia/reperfusion. Ilexonin A significantly decreased the infarct volume and improved neurological deficits in a dose­dependent manner. The expression levels of VEGF, Flk­1 and Nestin were significantly increased in the rats treated with Ilexonin A, compared with the rats administered with saline. Following treatment with Ilexonin A, a higher number of GFAP­positive astrocytes were found in the Ilexonin A­treated rats at 1, 3 and 7 days, compared with the rats exposed to ischemia only, however, there were fewer astrocytes at 14 days, compared with the ischemia group. Ilexonin A significantly decreased the protein expression of Iba­1. The results of the present study suggested that the protective effects of Ilexonin A were associated with revascularization, neuronal regeneration, and the regulation of astrocyte and microglia cell activation.

Rationale and design of the RT-AF study: Combination of rivaroxaban and ticagrelor in patients with atrial fibrillation and coronary artery disease undergoing percutaneous coronary intervention.

OBJECTIVE: Optimal antithrombotic strategy for patients with concomitant coronary artery disease and atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is still controversial, and the role of novel antithrombotic agents has nerve been tested. Therefore, the aim of this study is to evaluate and overall safety and efficacy profile of the combination of rivaroxaban and ticagrelor in this particular population. DESIGN: The RT-AF study is an open-label, randomized, active-controlled, multicenter clinical trial with up to 420 subjects enrolled in 5 centers. Eligible patients, who have a history or new onset paroxysmal, persistent, or permanent non-valvular AF, referred to the study centers with indications for PCI will be randomly assigned to receive triple therapy (including warfarin, clopidogrel and aspirin) or dual therapy (rivaroxaban and ticagrelor). All subjects will have clinical follow-up at discharge, at 30 days, 6 months and 12 months. The primary end point is major or clinically relevant non-major bleeding events at 12 months. The major secondary end point is the composite efficacy outcome of death, myocardial infarction, stent thrombosis and ischemic stroke. CONCLUSION: The study will be sufficiently powered to provide data primarily regarding the safety of dual therapy with rivaroxaban and ticagrelor over the traditional triple therapy in patients with AF undergoing PCI at 12 months. It will also provide important information regarding the efficacy of the two different antithrombotic regimens. (ClinicalTrials.gov identifier: NCT02334254).

Efficacy of coenzyme Q10 in mitigating spinal cord injury-induced osteoporosis.

Spinal cord injury (SCI)­induced osteoporosis may cause mild trauma to bone and increase the risk of bone fracture. The present study aimed to investigate the efficacy of coenzyme Q (CoQ10) on SCI­induced osteoporosis in rats. SCI was induced by surgical transection of the cord at the T10­12 level. Animals were treated with CoQ10 (10 mg/kg; intragastrically) daily from 12 h after the surgery and over 10 subsequent days. At the end of the experimental period, blood was collected from the animals and femurs and tibiae were removed for evaluation using biochemical assays. Treatment with CoQ10 prevented SCI­induced bone loss by rescuing the decreased levels of bone mineral density and bone mineral content observed in the SCI rats. Furthermore, CoQ10 administration reduced bone malondialdehyde levels with a concomitant increase in superoxide dismutase levels, thus alleviating SCI­induced oxidative injury. In addition, serum inflammatory cytokine levels were markedly increased in rats post­SCI, which was attenuated by treatment with CoQ10. Finally, the osteoclast­specific genes receptor activator of nuclear factor kappa­B ligand and cathepsin K were significantly upregulated and the osteoblast­specific gene core­binding factor alpha 1 in the femur was downregulated following SCI, which was effectively restored following treatment with CoQ10. The results suggested that CoQ10 treatment may be effective in attenuating SCI­induced osteoporosis.

[Treating coronary heart disease by acupuncture at neiguan (PC6) and xinahu (BL15): an efficacy assessment by SPECT].

OBJECTIVE: To evaluate the clinical efficacy of acupuncture combined single photon emission computed tomography (SPECT) in treating coronary heart disease (CHD) and its effect on the myocardial ischemia/perfusion and the recovery of heart functions. METHODS: Totally fifty-nine patients with confirmed CHD were randomly assigned to two groups, the acupuncture group (32 cases) and the nitroglycerine group (27 cases). Patients in the acupuncture group were electro-acupunctured at bilateral Neiguan (PC6) and Xinshu (BL15) for 30 min with the frequency of 2/15 Hz and the current strength 9 - 18 mA after myocardial imaging induced by routine exercises or drug load. 99mTc-MIBI 370 MBq was injected 15 min after needling. The myocardial perfusion imaging was performed immediately after needling. 99mTc-MIBI740 MBq was injected to those in the nitroglycerine group during routine exercises or drug load. The myocardial perfusion imaging was performed 5 min after injection. Patients were asked to sublingual administration of nitroglycerine 1 mg after the myocardial perfusion imaging was completed. 99mTc-MIBI 370 MBq was intravenously injected 5 min later, and myocardial perfusion imaging was performed 5 min after injection. RESULTS: There was statistical difference in changes of radioactive uptake between before and after treatment in the two groups (P < 0.05, P < 0.01). Both acupuncture and buccal administration of nitroglycerine could increase the blood perfusion of ischemic myocardium. But there was no statistical difference in the improvement of ischemic myocardial cells (t = 1.57, P > 0.05). CONCLUSION: Using SPECT could clearly display therapeutic effects of acupuncture on CHD, thus providing a new visible research method for CHD studies.

Heparin for patients with growth restricted fetus: a prospective randomized controlled trial.

OBJECTIVE: Heparin was hypothesized to facilitate the growth of the growth-restricted fetus. Our study was to assess the efficiency of heparin in treating fetus with growth restriction and to explore the possible mechanisms. METHODS: Seventy-three pregnant women were selected in this study. Based on regular treatments, patients randomly received either heparin or dan-shen combined with low-molecular weight dextrose. A serial ultrasonography and hematological measurements were performed on each patient at the enrolment and 7 days after the first treatment. Neonatal birth weight, 1-min Apgar score and gestational age were recorded. Placentas were collected for apoptotic indices. RESULTS: Heparin significantly improved maternal hemorrheological indices, fetal growth velocities and neonatal outcomes. It also reduced apoptosis in trophoblasts. CONCLUSIONS: Our results provide evidence that heparin significantly improves the growth of the growth-restricted fetus. The growth improvement is probably achieved by the changes in maternal hemorrheology and the attenuated apoptosis in trophoblasts.