Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice.

BACKGROUND: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). METHODS: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. RESULTS: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-ß-mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. CONCLUSIONS: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.

Tunable Contacts of Bi2 O2 Se Nanosheets MSM Photodetectors by Metal-Assisted Transfer Approach for Self-Powered Near-Infrared Photodetection.

Owing to the Fermi pinning effect arose in the metal electrodes deposition process, metal-semiconductor contact is always independent on the work function, which challenges the next-generation optoelectronic devices. In this work, a metal-assisted transfer approach is developed to transfer Bi2 O2 Se nanosheets onto the pre-deposited metal electrodes, benefiting to the tunable metal-semiconductor contact. The success in Bi2 O2 Se nanosheets transfer is contributed to the stronger van der Waals adhesion of metal electrodes than that of growth substrates. With the pre-deposited asymmetric electrodes, the self-powered near-infrared photodetectors are realized, demonstrating low dark current of 0.04 pA, high Ilight /Idark ratio of 380, fast rise and decay times of 4 and 6 ms, respectively, under the illumination of 1310 nm laser. By pre-depositing the metal electrodes on polyimide and glass, high-performance flexible and omnidirectional self-powered near-infrared photodetectors are achieved successfully. This study opens up new opportunities for low-dimensional semiconductors in next-generation high-performance optoelectronic devices.

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.

Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study.

BACKGROUND: Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. METHODS: A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n=13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. RESULTS: Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64-0.89, P = 8.03 × 10-4). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60-0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62-0.93, P = 8.76 × 10-3), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10-3), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10-3), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74-0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. CONCLUSIONS: This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms.

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.

Assessment of different thresholds of birthweight discordance for early neonatal outcomes: retrospective analysis of 2348 twin pregnancies.

BACKGROUND: The optimal threshold of birthweight discordance (BWD) remains controversial. This study aimed to evaluate the associations between BWD at different thresholds and early neonatal outcomes and to assess their predictive accuracy. METHODS: This was a retrospective cohort study using a birthweight data with the chorionicity information of 2348 liveborn twin pairs at a gestational age of ≥26 weeks, from 2012 to 2018. The percentage of BWD was calculated by dividing the actual birthweight difference by the weight of the larger twin and multiplying by 100. Outcomes of interest included neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome (NRDS), ventilator support and a composite outcome combining major morbidities and neonatal death. Logistic regression models were performed to estimate the association between neonatal outcomes and BWD with different thresholds (≥15.0%, ≥20.0%, ≥25% and ≥ 30%). Generalized estimated equation (GEE) models were used to address intertwin correlation. Restrictive cubic spline (RCS) models were established to draw the dose-response relationship between BWD and the odds ratios of outcomes. Clustered receiver operating characteristic (ROC) curve analyses were performed to assess the predictive accuracy. RESULTS: Of 2348 twin pairs, including 1946 dichorionic twin pairs and 402 monochorionic twin pairs, BWD was significantly associated with NICU admission, regardless of the thresholds used. The incidence of NRDS, ventilator support and the composite outcome were significantly higher when a threshold of ≥20% or greater was chosen. The dose-response relationship showed nonlinear growth in the risk of adverse neonatal outcomes with increasing BWD. ROC analyses showed a low significant AUROC of 0.569 (95% CI: 0.526-0.612) for predicting NICU admission but no significant AUROCs for predicting other outcomes. A BWD of ≥30% provided a moderate increase in the likelihood of NICU admission [positive likelihood ratio (LR+) = 5.77]. CONCLUSION: Although BWD is independently associated with adverse neonatal outcomes, it is not a single predictor for neonatal outcomes given the weak discriminative ability to predict neonatal outcomes. A cutoff of 30% is more practical for risk stratification among twin gestations.

Is there an optimal inter-delivery interval in women who underwent trial of labor after cesarean delivery (TOLAC)?

BACKGROUND: Inter-delivery interval (IDI) has been proven to be a factor associated with adverse maternal and neonatal outcomes. However, the optimal IDI in trial of labor after cesarean delivery (TOLAC) remains unclear. We aimed to investigate the association between IDI and major maternal and neonatal outcomes in women who underwent TOLAC. METHODS: A multicenter, retrospective cohort study including five hospitals was conducted between January 2018 and December 2019 in Foshan, China. This study included 1080 pregnant women with one or two cesarean deliveries who attempted a TOLAC. Data on maternal and neonatal outcomes were collected from the electronic record system. Maternal and neonatal outcomes in different groups of IDI were compared by univariate and multivariable analyses. RESULTS: A short IDI of < 24 months did not show a statistically significant association with uterine rupture in the univariate analysis (P = 0.668). In multivariable analysis, the incidences of postpartum hemorrhage (OR 19.6, 95% CI:4.4-90.9, P < 0.05), preterm birth (OR 5.5, 95% CI:1.5-21.3, P < 0.05), and low birth weight (OR 3.5, 95% CI:1.2-10.3, P < 0.05) were significantly increased in women with an IDI of < 24 months than in those with a normal interval (24-59 months). Infection morbidity (OR 1.8, 95% CI:1.4-7.9, P < 0.05), transfusion (OR 7.4, 95% CI:1.4-40.0, P < 0.05), and neonatal unit admission (OR 2.6, 95% CI:1.4-5.0, P < 0.05) were significantly increased in women with an IDI of 120 months or more than in those with a normal interval. Postpartum hemorrhage (P = 0.062) had a trend similar to that of a significant IDI of 120 months or more. We found no statistically significant difference in maternal and neonatal outcomes between 24-59 months and 60-119 months. CONCLUSIONS: An IDI of less than 24 months or 120 months or more increased the risk of major maternal and neonatal outcomes. We recommend that the optimal interval for women who underwent TOLAC should be 24 to 119 months.

An inter-delivery interval (IDI) that is too short or too long increases the risk of adverse maternal and neonatal outcomes. However, the optimal IDI for trial of labor after cesarean delivery (TOLAC) remains unclear. We performed a multicenter, electronic medical record-based, retrospective cohort study that included 1080 pregnant women who had one or two cesarean deliveries and underwent TOLAC. Data on maternal and neonatal outcomes were collected from the electronic record system. In multivariable analysis, the incidences of postpartum hemorrhage, preterm birth, and low birth weight were significantly increased in women with an IDI of < 24 months than in those with a normal interval (24­59 months). Infections, transfusion, and neonatal unit admission were significantly increased in women with an IDI of ≥ 120 months than in those with a normal interval. In conclusion, we found that an IDI < 24 months or ≥ 120 months increased the risk of major maternal and neonatal outcomes. We recommend that the optimal interval for women who underwent TOLAC should be 24 to 119 months.

First Report of Fusarium falciforme Causing Leaf Blight in Acacia mangium in China.

Acacia mangium Willd. is an important economic tree species with diverse uses and high ecological value, used in agriculture, restoration of degraded lands, for ornamental purposes, and commercial forestry (Leroy et al. 2009). This tree is widely cultivated in tropical and subtropical regions of China, such as Hainan, Guangdong, and Guangxi Provinces. In July 2021, a leaf blight of A. mangium saplings was observed with widespread distribution in the cultivation base of Hainan University (20° 3' 33″ N, 110°18' 56″ E) in Hainan Province, China. The initial symptoms were brown-to-black, irregular-shaped lesions on the leaf margin or tip. The entire leaf wilted and turned brown, leading to death and defoliation in the later periods of the disease (Fig. 1A-C). Of the 50 trees surveyed, the incidence rate was 68%. Small pieces of diseased tissue were collected from six different infected trees. The tissue surface was disinfested with 75% ethanol for 30 s, and 1% mercury chloride for 1 min, then rinsed three times with sterile distilled water. Infected tissues were placed onto potato dextrose agar (PDA) containing 0.01% streptomycin and incubated at 25°C for 7 days. Seventeen isolates were obtained by single-spore isolation on fresh PDA plates, and 15 isolates were identified morphologically as Fusarium spp. (Leslie et al. 2006). The colony surface was white, and the reverse side yellowish (Fig. 1D-E). Microconidia were oval or kidney-shaped, 6.2 to 9.6 × 2.5 to 6.3 µm (n=60). Macroconidia were sickle-shaped, with three to five septa, 19.5 to 41.2 × 3.7 to 6.8 µm (n=60) (Fig. 1F). For molecular identification, genomic DNA of three isolates (HNKFS01, HNKFS02, and HNKFS03) was extracted using E.Z.N.A.® HP Plant DNA kit (Omega Bio-Tek) and the internal transcribed spacer of rDNA (ITS), translation elongation factor 1-α (EF1-α), RNA polymerase II beta subunit (RPB2), and ß-tubulin (TUB) regions were amplified and sequenced using primers ITS1F/ITS4, EF-1/EF-2, RPB2-5F2/11aR, and T1/T2, respectively (O'Donnell et al. 2010; O'Donnell and Cigelnik 1997; White et al. 1990). Sequences were deposited in GenBank for ITS (OM289152 to OM289154), EF1-α (OM289155 to OM289157), RPB2 (ON193365 to ON193367), and TUB (ON193314 to ON193316). Using BLASTn, ITS sequences matched 98.88% (532/538 bp) to F. falciforme (MT114705), EF1-α sequences matched 99.58% (703/706 bp; MK752502), RPB2 sequences matched 98.31% (988/1005 bp; MW691193), and TUB gene sequences matched 99.10% (332/335 bp; OK087483). Polyphasic identification with ITS, EF1-α, RPB2, and TUB sequences revealed a 98.51% match with F. falciforme (NRRL 32729) sequences in Fusarium-ID databases. Pathogenicity of 15 isolates was determined by using healthy one-year-old A. mangium seedlings. Three leaves from each seedling were selected to test. Mycelial plugs of each isolate were inoculated on one leaf (three plugs per leaf). An agar plug without the fungus was placed on a leaf as a control. The pathogenicity tests were repeated twice. After 7 days of incubation in a greenhouse, all leaves inoculated with the pathogen showed black lesions with white flocculent hyphae (Fig. 1H), while control leaves were asymptomatic (Fig. 1G). Typical colonies of F. falciforme were isolated from all inoculated leaves, and identified by morphology and ITS, EF1-α, RPB2, and TUB sequence analysis, fulfilling Koch´s postulates. To our knowledge, this is the first report of F. falciforme causing leaf blight in A. mangium in China and the world. This disease can lead to death of A. mangium, which seriously restricts commercialization, requiring that management strategies be adopted.

Association between IVF/ICSI treatment and preterm birth and major perinatal outcomes among dichorionic-diamnionic twin pregnancies: A seven-year retrospective cohort study.

INTRODUCTION: This study aimed to evaluate the preterm birth and additional perinatal outcomes between spontaneous and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) dichorionic-diamnionic (DCDA) twin pregnancies. MATERIAL AND METHODS: This retrospective cohort study was conducted in a tertiary university-affiliated medical center. All women with DCDA twin pregnancies were considered for inclusion. The primary outcome of interest was preterm birth <37 weeks of gestation and secondary outcomes included spontaneous preterm birth, iatrogenic (induced) preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, preterm premature rupture of membranes (PPROM), intrahepatic cholestasis of pregnancy, placenta previa, neonatal intensive care unit (NICU) admission, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity. These outcomes were compared between IVF/ICSI and spontaneous twin pregnancies. Multivariable logistic regressions were used to adjust for confounders. General estimated equation models were used to address intertwin correlation. RESULTS: A total of 1297 twin pregnancies, including 213 spontaneous and 1084 IVF/ICSI DCDA pregnancies, met the inclusion criteria. Women with IVF/ICSI pregnancies were older and had higher body mass index, adherence with prenatal care and proportion of nulliparity. After adjustment for confounders, IVF/ICSI pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation (adjusted odds ratio [aOR] 1.72; 95% CI 1.24-2.39), iatrogenic preterm birth <37 weeks of gestation (aOR 1.41; 95% CI 1.00-1.97) as well as NICU admission (aOR 1.34; 95% CI 1.00-1.80). IVF/ICSI pregnancies were associated with a decrease in PPROM (aOR 0.64; 95% CI 0.42-0.99). There were no differences between IVF/ICSI and spontaneous DCDA pregnancies in terms of spontaneous preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity. CONCLUSIONS: IVF/ICSI DCDA twin pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation, iatrogenic preterm birth <37 weeks of gestation, and NICU admission but with a decrease in PPROM. Other outcomes were comparable between IVF/ICSI and spontaneous DCDA twin pregnancies. Multicenter studies with adequate power remain warranted.

Maternal and neonatal outcomes in transverse and vertical skin incision for placenta previa : Skin incision for placenta previa.

BACKGROUND: Placenta previa, a serious obstetric issue, should be managed by experienced teams. The safe and appropriate mode of delivery for placenta previa is by cesarean delivery. However, no studies were found comparing either maternal or neonatal outcomes for different skin incision in women with placenta previa. The aim of this study was to compare maternal and neonatal outcomes by skin incision types (transverse compared with vertical) in a large cohort of women with placenta previa who were undergoing cesarean delivery. METHODS: This was a retrospective cohort study carried out between January 2014 and June 2019. All pregnant women with placenta previa had confirmed by ultrasonologist before delivery and obstetrician at delivery. The primary outcome was the estimated blood loss during the surgery and within the first 24 hours postoperatively. Mean (standard deviation), median (interquartile range) or frequency (percentage) was reported to variables. Appropriate parametric and nonparametric tests were used to analyses. RESULTS: The study included 1098 complete records, 332 (30.24%) cases in the vertical skin incision group and 766 (69.76%) cases in the transverse skin incision group. Those with vertical incision showed a higher percentage of preterm delivery, anterior placenta, abnormally invasive placenta, and history of previous cesarean delivery, and a lower percentage of first pregnancy, in vitro fertilization, and emergency cesarean delivery. After controlling for confounding factors, higher incidence of post-partum hemorrhage (OR 5.47, 95% CI 3.84-7.79), maternal intensive care unit (OR 4.30, 95% CI 2.86-6.45), transfusion (OR 5.97, 95% CI 4.15-8.58), and 5-min APGAR< 7 (OR 9.03, 95% CI 1.83-44.49), a more estimated blood loss (ß 601.85, 95%CI 458.78-744.91), and a longer length of hospital stay after delivery (ß 0.54, 95%CI 0.23-0.86) were found in the vertical skin incision group. CONCLUSIONS: Our data demonstrated that transverse skin incision group showed the better perinatal outcomes in women with placenta previa. Future collaborative studies are needed to be done by centers for placenta previa to have a better understanding of the characteristics and the outcomes of the disease in the choosing skin incision.

Should singleton birth weight standards be applied to identify small-for-gestational age twins?: analysis of a retrospective cohort study.

BACKGROUND: Twin birth weight percentiles are less popular in clinical management among twin pregnancies compared with singleton ones in China. This study aimed to compare the incidence and neonatal outcomes of small for gestational age (SGA) twins between the use of singleton and twin birth weight percentiles. METHODS: This was a retrospective cohort study of 3,027 pregnancies with liveborn twin pairs at gestational age of > 28 weeks. The newborns were categorized as SGA when a birthweight was less than the 10th percentile based on the singleton and twin references derived from Chinese population. Logistic regression models with generalized estimated equation (GEE) were utilized to evaluate the association between SGA twins and neonatal outcomes including neonatal unit admission, neonatal jaundice, neonatal respiratory distress (NRDS), neonatal asphyxia, ventilator support, hypoxic ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intracranial hemorrhage (ICH), culture-proven sepsis, neonatal death within 28 days after birth as well as the composite outcome. RESULTS: The incidence of SGA was 33.1 % based on the singleton reference and 7.3 % based on the twin reference. Both of SGA newborns defined by the singleton and twin references were associated with increases in neonatal unit admission, neonatal jaundice and ventilator support. In addition, SGA newborns defined by the twin reference were associated with increased rates of BPD (aOR, 2.61; 95 % CI: 1.18-5.78) as well as the severe composite outcome (aOR, 1.93; 95 % CI: 1.07-3.47). CONCLUSIONS: The use of singleton birth weight percentiles may result in misdiagnosed SGA newborns in twin gestations and the twin birth weight percentiles would be more useful to identify those who are at risk of adverse outcomes.

Anesthetic management in cesarean delivery of women with placenta previa: a retrospective cohort study.

BACKGROUND: The incidence of placenta preiva is rising. Cesarean delivery is identified as the only safe and appropriate mode of delivery for pregnancies with placenta previa. Anesthesia is important during the cesarean delivery. The aim of this study is to assess maternal and neonatal outcomes of patients with placenta previa managed with neuraxial anesthesia as compared to those who underwent general anesthesia during cesarean delivery. METHODS: A retrospective cohort study was performed of all patients with placenta preiva at our large academic institution from January 1, 2014 to June 30, 2019. Patients were managed neuraxial anesthesia and general anesthesia during cesarean delivery. RESULTS: We identified 1234 patients with placenta previa who underwent cesarean delivery at our institution. Neuraxial anesthesia was performed in 737 (59.7%), and general anesthesia was completed in 497 (40.3%) patients. The mean estimated blood loss at neuraxial anesthesia of 558.96 ± 42.77 ml were significantly lower than the estimated blood loss at general anesthesia of 1952.51 ± 180 ml (p < 0.001). One hundred and forty-six of 737 (19.8%) patients required blood transfusion at neuraxial anesthesia, whereas 381 out of 497 (76.7%) patients required blood transfusion at general anesthesia. The rate neonatal asphyxia and admission to NICU at neuraxial anesthesia was significantly lower than general anesthesia (2.7% vs. 19.5 and 18.2% vs. 44.1%, respectively). After adjusting confounding factors, blood loss was less, Apgar score at 1- and 5-min were higher, and the rate of blood transfusion, neonatal asphyxia, and admission to NICU were lower in the neuraxial group. CONCLUSIONS: Our data demonstrated that neuraxial anesthesia is associated with better maternal and neonatal outcomes during cesarean delivery in women with placenta previa.

Prospective association of metal levels with gestational diabetes mellitus and glucose: A retrospective cohort study from South China.

OBJECTIVE: To explore the prospective correlation between serum metals before 24 weeks' gestation and gestational diabetes mellitus (GDM) or glucose in the late second trimester among southern Chinese pregnant women. METHODS: A total of 8169 pregnant women were included in our retrospective cohort study. Logistic regression was used to investigate the relationships between metals (Manganese [Mn], copper [Cu], lead [Pb], calcium [Ca], zinc [Zn], magnesium [Mg]) and GDM. Quantile regression was performed to detect the shifts and associations with metals and three time-points glucose distribution of oral glucose tolerance test (OGTT) focused on the 10th, 50th, and 90th percentiles. Weighted quantile sum (WQS) regression was used to explore the relationship of metal mixtures and GDM as well as glucose. RESULTS: Maternal serum concentrations of metals were assessed at mean 16.55 ± 2.92 weeks' gestation. Women with under weight might have 25% decreased risk of GDM for every 50% increase in Cu concentration within the safe limits. A 50% increase in Mn and Zn levels was related to a 0.051 µmol/L (95% CI: 0.033-0.070) and 0.059 µmol/L (95% CI: 0.040-0.079) increase in mean fasting plasma glucose of OGTT (OGTT0), respectively. The magnitude of association with Mn was smaller at the upper tail of OGTT0 distribution, while the magnitude of correlation with Zn was greater at the upper tail. However, there was a 0.012 mmol/L (95% CI: -0.017 to -0.008), 0.028 mmol/L (95% CI: -0.049 to -0.007), and 0.036 mmol/L (95% CI: -0.057 to -0.016) decrease in mean OGTT0 levels for every 50% increase in Pb, Ca, and Mg, respectively. The negative association of Pb, Ca, and Mg was greater at the lower tail of OGTT0 distribution. No significant relationship was observed in Cu and mean OGTT0 level (-0.010 mmol/L, 95% CI: -0.021 to 0.001), however, it showed a protective effect at the upper tail (-0.034 mmol/L, 95% CI: -0.049 to -0.017). No obvious correlation was found between metals and postprandial glucose levels (OGTT1 and OGTT2 from OGTT). The WQS index was significantly related to OGTT0 (P < 0.001). The contribution of Mn (80.19%) to metal mixture index was the highest related to OGTT0, followed by Cu (19.81%). CONCLUSIONS: Higher Mn and Zn but lower Pb, Ca, and Mg concentrations within a certain range before 24 weeks' gestation might prospectively impair fasting plasma glucose during pregnancy; a greater focus is required on Mn. It could provide early markers of metal for predicting later glucose and suggest implement intervention for pregnant women.

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.

The effect of gestational weight gain on perinatal outcomes among Chinese twin gestations based on Institute of Medicine guidelines.

BACKGROUND: Gestational weight gain (GWG) has implications for perinatal outcomes, the guidelines for maternal weight gain, however, remain understudied among twin pregnancies. This study aimed to assess the associations between perinatal outcomes and GWG among twin pregnancies, based on the US institute of Medicine (IOM) 2009 guidelines. METHODS: A retrospective cohort study of pregnant women with viable twins ≥26 weeks of gestation, was conducted in Foshan, China, during July 2015 and June 2018. Maternal BMI was categorized based on Chinese standard and GWG was categorized as below, within and above the IOM 2009 recommendations. Underweight women were excluded for analysis. Perinatal outcomes were compared among these groups. To assess the independent impact of GWG on the perinatal outcomes, conventional multivariable regression and general estimated equation (GEE) were utilized for maternal outcomes and neonatal outcomes, respectively. RESULTS: A total of 645 mothers with twin pregnancies were included, of whom 15.0, 41.4 and 43.6% gained weight below, within and above guidelines, respectively. Compared to weight gain within guidelines, inadequate weight gain was associated with increased risks in spontaneous preterm birth < 37 weeks (aOR:3.55; 95% CI: 1.73-7.28) and < 35 weeks (aOR:2.63; 95% CI: 1.16-5.97). Women who gained weight above guidelines were more likely to have gestational hypertension disorder (aOR: 2.36; 95% CI: 1.32-4.21), pre-eclampsia (aOR: 2.59; 95% CI: 1.29-5.21) and have fetuses weighted >90th percentile and less likely to have fetuses weighted < 2500 g and < 1500 g. CONCLUSIONS: Maintenance of gestational weight gain within the normal range could decrease the risk of adverse perinatal outcomes. However, the causality between pre-eclampsia and gestational weight gain requires further investigations.

Associations of Childhood Maltreatment with Single and Multiple Suicide Attempts among Older Chinese Adolescents.

OBJECTIVES: To test, among older Chinese adolescents, the associations of childhood maltreatment with single and multiple suicide attempts and whether these associations vary in relation to the presence of sleep disturbance. STUDY DESIGN: We analyzed data collected from 10th to 12th graders from 7 randomly selected provinces of China in the 2015 School-based Chinese Adolescents Health Survey. There were 83 200 students who were invited to participate, and 75 715 students' questionnaires were completed and qualified for the survey. Adjusted multinomial logistic regression models were conducted to evaluate the associations of childhood maltreatment with suicide attempts. RESULTS: Compared with no suicide attempts, each type of adjusted childhood maltreatment (physical abuse, emotional abuse, sexual abuse, physical neglect, or emotional neglect) was associated with an increased risk of single and multiple suicide attempts (P < .05). The magnitude of the aORs in multiple suicide attempters was greater than those in single suicide attempters. Moreover, the adjusted interaction effects for a single suicide attempt between each type of childhood maltreatment and sleep disturbance were all statistically significant in the multivariable multinomial logistic regression models (P < .001). However, the adjusted interaction effects for multiple suicide attempts were not significant (P > .05). CONCLUSIONS: Maltreatment during one's childhood is associated with an increased risk of single and multiple suicide attempts among older Chinese adolescents. Sleep disturbances play a moderating role in these associations for a single suicide attempt.

Poor sleep and reduced quality of life were associated with symptom distress in patients receiving maintenance hemodialysis.

BACKGROUND: The quality of life in patients receiving chronic hemodialysis is compromised despite of the substantial achievements in treatments. Quality of life in hemodialysis patients have been shown to be associated with decreased survival and increased hospitalization. Therefore, it is necessary to incorporate the managements of symptoms and patient self-perceived well-being as measurements of effective treatments for these patients. METHODS: A survey of symptom distress, quality of sleep and quality of life was performed in 301 maintenance hemodialysis patients using Dialysis Symptom Index, Short Form-36, and Pittsburgh Quality of Sleep Index table. Patients were recruited from five hospitals in Guangdong area of China by convenience sampling. RESULTS: The prevalence of various symptoms in maintenance hemodialysis patients was between 23.3 and 80.4 %. These patients had compromised sleep and poor quality of life. Moreover, poor quality of sleep and impaired quality of life were associated with high symptom burden of these patients. CONCLUSION: The patients receiving chronic hemodialysis generally have heavy symptom distress, which could contribute to the disturbed sleep and impaired quality of life of these patients. Measurements of clinical outcomes for hemodialysis patients should include the management of symptoms and morbidity. The ultimate goal of treatments is to improve patient self-perceived quality of life.

Identification of circular RNAs regulating cardiomyocyte proliferation in neonatal pig hearts.

Little is known about the expression patterns and functions of circular RNAs (circRNAs) in the heart of large mammals. In this study, we examined the expression profiles of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in neonatal pig hearts. Pig heart samples collected on postnatal days 1 (P1), 3 (P3), 7 (P7), and 28 (P28) were sent for total RNA sequencing. Our data revealed a total of 7,000 circRNAs in the 24 pig hearts. Pathway enrichment analysis of hallmark gene sets demonstrated that differentially expressed circRNAs were engaged in different pathways. The most significant difference was observed between P1 and the other 3 groups (P3, P7, and P28) in pathways related to cell cycle and muscle development. Out of the 10 circRNAs that were validated through real-time quantitative PCR to verify their expression, 6 exhibited significant effects on cell cycle activity in human induced pluripotent stem cell-derived cardiomyocytes following small interfering RNA-mediated knockdown. circRNA-miRNA-mRNA networks were constructed to understand the potential mechanisms of circRNAs in the heart. In conclusion, our study provided a data set for exploring the roles of circRNAs in pig hearts. In addition, we identified several circRNAs that regulate cardiomyocyte cell cycle.

Generation of a Human Induced Pluripotent Stem Cell Line Expressing a Magnetic Resonance Imaging Reporter Gene.

The objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC-CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC-CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC- FHCOE) and hiPSC-CMs overexpressing FHC (hiPSC-CM-FHCOE) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC-CM-Control. Furthermore, hiPSC-CM-FHCOE presented robust contrast and lower T2* values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC-CM-FHCOE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC-CM-FHCOE cells exhibited clear signals in the hearts with lower T2* and rapid signal decay. Collectively, data from this proof-of-concept study demonstrated that endogenous labeling with FHC in hiPSC-CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC-CMs in the hearts of live animals.

Peptide-Guided Nanoparticle Drug Delivery for Cardiomyocytes.

BACKGROUND: Nanoparticles (NPs) have been extensively utilized as a drug delivery system to control the release of therapeutic agents to treat cardiac injuries. However, despite the advantages of utilizing NP-based drug delivery for treating heart diseases, the current delivery system lacks specificity in targeting the cardiac tissue, thus limiting its application. METHODS: We created three linear peptides, each consisting of 16-24 amino acids. These peptides were conjugated on the surface of NPs, resulting in the formation of cardiac targeting peptide (CTP)-NPs (designated as CTP-NP1, CTP-NP2, and CTP-NP3). To assess their effectiveness, we compared the binding efficiency of these three CTP-NPs to human and mouse cardiomyocytes. Additionally, we determined their distribution 24 h after injecting the CTP-NPs intravenously into adult C57BL/6J mice. RESULTS: When compared to control NPs without CTP (Con-NPs), all three CTP-NPs exhibited significantly increased binding affinity to both human and mouse cardiomyocytes in vitro and enhanced retention in mouse hearts in vivo. A thorough assessment of the heart sections demonstrated that the binding specificity of CTP-NP3 to cardiomyocytes in vivo was significantly greater than that of Con-NPs. None of the three CTP-NPs were proven to cause cardiomyocyte apoptosis. CONCLUSIONS: Biocompatible and safe CTP-NP3 can target the heart via binding to cardiomyocytes. This approach of targeting specific molecules-coated NPs may help in delivering therapeutic compounds to cardiomyocytes for the treatment of heart diseases with high efficacy and low toxicity to other tissues.