A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery.

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

Effects of paternal deprivation on empathetic behavior and the involvement of oxytocin receptors in the anterior cingulate cortex.

Paternal deprivation (PD) impairs social cognition and sociality and increases levels of anxiety-like behavior. However, whether PD affects the levels of empathy in offspring and its underlying mechanisms remain unknown. The present study found that PD increased anxiety-like behavior in mandarin voles (Microtus mandarinus), impaired sociality, reduced the ability of emotional contagion, and the level of consolation behavior. Meanwhile, PD reduced OT neurons in the paraventricular nucleus (PVN) in both male and female mandarin voles. PD decreased the level of OT receptor (OTR) mRNA in the anterior cingulate cortex (ACC) of male and female mandarin voles. Besides, OTR overexpression in the ACC reversed the PD-induced changes in anxiety-like behavior, social preference, emotional contagion, and consolation behavior. Interference of OTR expression in the ACC increased levels of anxiety-like behaviors, while it reduced levels of sociality, emotional contagion, and consolation. These results revealed that the OTR in the ACC is involved in the effects of PD on empathetic behaviors, and provide mechanistic insight into how social experiences affect empathetic behaviors.

A sonographic endometrial thickness <7 mm in women undergoing in vitro fertilization increases the risk of placenta accreta spectrum.

BACKGROUND: The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for placenta accreta spectrum could enable early treatment and improved outcomes. Endometrial thickness plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of endometrial thickness on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of endometrial thickness on placenta accreta spectrum. OBJECTIVE: This study aimed to evaluate the association between preimplantation endometrial thickness and the occurrence of placenta accreta spectrum in women undergoing assisted reproductive technology cycles. STUDY DESIGN: A total of 4637 women who had not undergone previous cesarean delivery and who conceived by in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 and December 2020 were included in this study. To explore the relationship between endometrial thickness and placenta accreta spectrum, we used smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between endometrial thickness and placenta accreta spectrum while adjusting for potential confounding factors. Propensity score matching was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we used causal mediation effect analysis to investigate the mediating role of endometrial thickness in the relationship between gravidity and ovarian stimulation protocol and the occurrence of placenta accreta spectrum. RESULTS: Among the 4637 women included in this study, pregnancies with placenta accreta spectrum (159; 3.4%) had significantly thinner endometrial thickness (non-placenta accreta spectrum, 10.08±2.04 mm vs placenta accreta spectrum, 8.88±2.21 mm; P<.001) during the last ultrasound before embryo transfer. By using smooth curve fitting, it was found that changes in endometrial thickness had a significant effect on the incidence of placenta accreta spectrum up to a thickness of 10.9 mm, beyond which the effect plateaued. Then, the endometrial thickness was divided into the following 4 groups: ≤7, >7 to ≤10.9, >10.9 to ≤13, and >13 mm. The absolute rates of placenta accreta spectrum in each group were 11.91%, 3.73%, 1.35%, and 2.54%, respectively. Compared with women with an endometrial thickness from 10.9 to 13 mm, the odds of placenta accreta spectrum increased from an adjusted odds ratio of 2.27 (95% confidence interval, 1.33-3.86) for endometrial thickness from 7 to 10.9 mm to an adjusted odds ratio of 7.15 (95% confidence interval, 3.73-13.71) for endometrial thickness <7 mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 11.80; 95% confidence interval, 7.65-18.19). Moreover, endometrial thickness <7 mm was still an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 3.91; 95% confidence interval, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on placenta accreta spectrum were mediated by endometrial thickness. CONCLUSION: The findings of our study indicate that thin endometrial thickness is an independent risk factor for placenta accreta spectrum in women without previous cesarean delivery undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than that of placenta previa. Furthermore, our results demonstrate that endometrial thickness plays a significant mediating role in the relationship between gravidity or ovarian stimulation protocol and placenta accreta spectrum.

Chronic stress and stressful emotional contagion affect the empathy-like behavior of rats.

Empathy is a potential motivation for prosocial behaviors that is related to many psychiatric diseases, such as major depressive disorder; however, its neural mechanisms remain unclear. To elucidate the relationship between empathy and stress, we established a chronic stress contagion (SC) procedure combined with chronic unpredictable mild stress (CUMS) to investigate (1) whether depressive rats show impaired empathy-like behavior toward fearful conspecifics, (2) whether frequent social contact with normal familiar conspecifics (social support) alleviates the negative effects of CUMS, and (3) the effect of long-term exposure to a depressed partner on emotional and empathic responses in normal rats. We found that the CUMS group showed less empathy-like behavior in the social transfer of fear model (STFM), as indicated by less social interaction with the demonstrator and reduced freezing behavior in the fear-expression test. Social contact partially alleviated depression-like behaviors and the negative effect of CUMS in the fear-transfer test. The normal rats who experienced stress contagion from daily exposure to a depressed partner for 3 weeks showed lower anxiety and increased social response in the fear-transfer test than the control group. We concluded that chronic stress impairs empathy-like behaviors, while social contact partially buffers the effect of CUMS. Thus, social contact or contagion of stress is mutually beneficial to both stressed individuals and nonstressed partners. Higher dopamine and lower norepinephrine levels in the basolateral amygdala probably contributed to these beneficial effects.

Involvement of Serotonergic Projections from the Dorsal Raphe to the Medial Preoptic Area in the Regulation of the Pup-Directed Paternal Response of Male Mandarin Voles.

Male mammals display different paternal responses to pups, either attacking or killing the young offspring, or contrastingly, caring for them. The neural circuit mechanism underlying the between-individual variation in the pup-directed responsiveness of male mammals remains unclear. Monogamous mandarin voles were used to complete the present study. The male individuals were identified as paternal and infanticidal voles, according their behavioral responses to pups. It was found that the serotonin release in the medial preoptic area (MPOA), as well as the serotonergic neuron activity, significantly increased upon licking the pups, but showed no changes after attacking the pups, as revealed by the in vivo fiber photometry of the fluorescence signal from the 5-HT 1.0 sensor and the calcium imaging indicator, respectively. It was verified that the 5-HTergic neural projections to the MPOA originated mainly from the ventral part of the dorsal raphe (vDR). Furthermore, the chemogenetic inhibition of serotonergic projections from the vDR to the MPOA decreased the paternal behaviors and shortened the latency to attack the pups. In contrast, the activation of serotonergic neurons via optogenetics extended the licking duration and inhibited infanticide. Collectively, these results elucidate that the serotonergic projections from the vDR to the MPOA, a previously unrecognized pathway, regulate the paternal responses of virgin male mandarin voles to pups.

Paraventricular Nucleus Oxytocin Subsystems Promote Active Paternal Behaviors in Mandarin Voles.

Paternal care plays a critical role in the development of brain and behaviors in offspring in monogamous species. However, the neurobiological mechanisms, especially the neuronal circuity, underlying paternal care is largely unknown. Using socially monogamous male mandarin voles (Microtus mandarinus) with high levels of paternal care, we found that paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) or nucleus accumbens (NAc) oxytocin (OT) neurons are activated during paternal care. Chemogenetic activation/inhibition of the PVN OT projection to VTA promoted/decreased paternal care, respectively. Chemogenetic inhibition of the PVN to VTA OT pathway reduced dopamine (DA) release in the NAc of male mandarin voles during licking and grooming of pups as revealed by in vivo fiber photometry. Optogenetic activation/inhibition of the VTA to NAc DA pathway possibly enhanced/suppressed paternal behaviors, respectively. Furthermore, chemogenetic activation/inhibition of PVN to NAc OT circuit enhanced/inhibited paternal care. This finding is a first step toward delineating the neuronal circuity underlying paternal care and may have implications for treating abnormalities in paternal care associated with paternal postpartum depression or paternal abuse.SIGNIFICANCE STATEMENT Paternal behavior is essential for offspring survival and development in some mammalian species. However, the circuit mechanisms underlying the paternal brain are poorly understood. We show that manipulation of paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) oxytocin (OT) projections as well as VTA to nucleus accumbens (NAc) DA projections promote paternal behaviors. Inhibition the PVN to VTA OT pathway reduces DA release in the NAc during pup licking and grooming. PVN to NAc OT circuit is also essential for paternal behaviors. Our findings identify two new neural circuits that modulate paternal behaviors.

The association of serum total bile acid with new-onset hypertension during pregnancy.

BACKGROUND: There has been considerable interest in the interrelationship between the liver and hypertension. The relationship between serum total bile acid (TBA) and hypertension has been reported. Moreover, intrahepatic cholestasis of pregnancy was correlated to gestation hypertension. However, the association between maternal serum TBA level in the normal range and new-onset hypertension disorders during pregnancy remains unclear. The present study aimed to evaluate the relationship between maternal serum TBA level in the normal range and the risk, disease severity and adverse pregnancy outcomes of new-onset hypertension during pregnancy. METHOD: Using the electronic medical records on all pregnant women from the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between 2014 and 2020, we conducted a retrospective cohort study of 2581 singleton pregnant women with maternal serum TBA levels in the normal range. Patients were grouped into the non-hypertension during pregnancy (1071), gestational hypertension (480) and preeclampsia (1030) groups. RESULT: We found that maternal serum TBA levels were significantly higher in the preeclampsia and gestational hypertension groups than in the non-hypertension group (p < 0.01). Multiple logistic regression analysis showed that TBA level was independently and significantly associated with preeclampsia and gestational hypertension (odds ratio: 1.37, 95% confidence interval [CI]: 1.27-1.48, p = 0.001, odds ratio: 1.34, 95% confidence interval [CI]: 1.24-1.46, p = 0.005, respectively). Moreover, elevated TBA level was positively associated with the risk of severe PE and negatively with mild PE (p < 0.01). In addition, maternal serum TBA levels were negatively related to birth weight (p < 0.001). CONCLUSIONS: These results suggest that maternal serum TBA in the normal range also might be a valuable biomarker for disease severity in preeclampsia and gestational hypertension. Additionally, our results also indicate associations of serum total bile acid levels in the normal range with an increased risk of fetal growth restriction and low birth weight among offspring. These results suggest that TBA could serve as a prognostic biomarker for new-onset hypertension during pregnancy.

Association between the second-stage duration of labor and perinatal outcomes in women with a prior cesarean delivery.

BACKGROUND: The cesarean delivery (CD) rate has been increasing globally. Trial of labor after cesarean delivery (TOLAC) has been used as a key method for the reduction of the CD rate. Little is known, however, about the association between the second-stage duration of TOLAC and adverse maternal and neonatal outcomes. This study evaluated the association between perinatal outcomes and the duration of second-stage labor in women undergoing TOLAC. METHODS: A 10-year retrospective cohort study was performed at the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between January 2010 and January 2020. Women undergoing TOLAC who reached the second stage of labor were included in this study. Duration of the second stage of labor was examined as a categorical variable (group I: <0.5 h, group II: 0.5-2 h and group III: ≥2 h) and as a continuous variable to evaluate the association with adverse perinatal outcomes by using multivariable regression models and a Cox proportional hazards regression model adjusting for potential confounders. RESULTS: Of the 1,174 women who met the inclusion criteria, the median (interquartile range) length of the second stage was 0.5 h (0.3-0.9 h). Among them, 1,143 (97.4%) delivered vaginally and 31 underwent an unplanned CD. As the second-stage duration increased, operative vaginal delivery (OVD), CD, and postpartum hemorrhage (PPH) rates increased. Women in group III had higher risks of OVD (aOR = 11.34; 95% CI [5.06-25.41]), CD (aOR = 4.22; 95% CI [1.32-13.43]), and PPH (aOR = 2.43; 95% CI [1.31-4.50]) compared with group I. Correspondingly, blood loss and the oxytocin used to treat PPH increased significantly, while the postpartum hemoglobin reduced significantly in group III compared with group I. The incidence of uterine rupture, uterine atony, cervical laceration, red blood cell transfusion, and intensive care unit admission were similar in all three groups. Neonatal outcomes were not affected by the second-stage duration. CONCLUSIONS: Women undergoing TOLAC with second-stage duration of ≥2 h have higher odds of OVD, unplanned intrapartum CD, and PPH.

Maternal age at first cesarean delivery related to adverse pregnancy outcomes in a second cesarean delivery: a multicenter, historical, cross-sectional cohort study.

BACKGROUND: To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. METHODS: This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. RESULTS: The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25-29, 30-34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12-2.01), placenta previa (aOR, 1.349; 95% CI, 1.07-1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24-3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05-2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21-1.91) in the second cesarean compared with the reference group (aged 25-29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08-2.24), placental abruption (aOR, 6.464, 95% CI, 1.33-31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43-44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95-24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53-12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54-220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54-5.17) compared with the reference group (aged 25-29 years). CONCLUSIONS: Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Effect of types of placenta previa on maternal and neonatal outcomes: a 10-year retrospective cohort study.

PURPOSE: Through this study, we aimed to evaluate the effects of different types of placenta previa (PP) on maternal and neonatal outcomes. METHODS: This study was conducted in The Third Affiliated Hospital of Guangzhou Medical University and Tongji Hospital between January 2009 and 2019. PP was traditionally classified into four types, namely low-lying placenta, marginal, partial, and complete PP. Previous studies have classified PP into two types, namely low-lying placenta and PP. Based on our clinical experience, we proposed the classification of PP into three types, for the first time, which included low-lying placenta, "marpartial" (marginal and partial) PP, and complete PP. Multivariate logistic regression analysis was performed to determine the effects of different types of PP on maternal and neonatal outcomes. RESULTS: In total, 4490 singleton pregnancies were complicated with PP. In the four-classification method, compared with women with low-lying placenta, women with complete PP had a risk of placenta accrete spectrum disorders, postpartum hemorrhage (PPH), hemorrhagic shock, severe PPH, blood transfusion, hysterectomy, puerperal infection, preterm labor, NICU admission, and low birth weight. There was no difference in maternal and neonatal outcomes between marginal and partial PP, except for increased chances of preterm labor and low birth weight in partial PP. In the two-classification method, PP was the risk factor for most of the adverse maternal and neonatal outcomes, compared with low-lying placenta. CONCLUSION: Complete PP and low-lying placenta were associated with the highest and lowest risks of adverse pregnancy outcomes, respectively, whereas clinically similar outcomes were observed between marginal and partial PP. The three-classification of PP may be practical from the clinical perspective.

Effect of previous placenta previa on outcome of next pregnancy: a 10-year retrospective cohort study.

BACKGROUND: To determine the effects of previous placenta previa on the maternal and neonatal outcomes of the next pregnancy. METHODS: This 10-year retrospective cohort study was conducted in the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between January 2009 and 2018. We retrospectively analyzed the effects of a previous singleton pregnancy in women with and without placenta previa on the outcomes of the subsequent pregnancy. To control for confounders, we used multiple logistic regression models. RESULTS: A total of 57,251 women with singleton pregnancies gave birth during the 10-year study period. Among them, 6070 women had two consecutive births. For the first pregnancy, 1603 women delivered by cesarean delivery and 4467 by vaginal delivery. Among women with a history of cesarean delivery, placenta previa was an independent risk factor for hemorrhage (adjusted odds ratio [aOR]: 2.25, 95% confidence interval [CI]: 1.1-4.62), placenta accreta spectrum (PAS) disorders (aOR: 4.11, 95% CI: 1.68-10.06), and placenta previa (aOR: 6.24, 95% CI: 2.85-13.67) during the subsequent pregnancy. Puerperal infection, blood transfusion, and perinatal outcomes did not significantly differ between women with a history of placenta previa and women without this history. Among women with a history of vaginal delivery, placenta previa increased the risk of PAS disorders (aOR: 5.71, 95% CI: 1.81-18.03) and placenta previa (aOR: 4.14, 95% CI: 1.07-16.04) during the subsequent pregnancy. There was no significant difference between the two groups in terms of hemorrhage, blood transfusion, puerperal infection, and perinatal outcomes. CONCLUSIONS: Women with a history of placenta previa are at risk for adverse outcomes such as postpartum hemorrhage, PAS disorders, and placenta previa in the subsequent pregnancy.

Development and Validation of Predictive Models for Vaginal Birth After Cesarean Delivery in China.

BACKGROUND The rate of delivery by cesarean section is rising in China, where vaginal birth after cesarean (VBAC) is in its early stages. There are no validated screening tools to predict VBAC success in China. The objective of this study was to identify the variables predicting the likelihood of successful VBAC to create a predictive model. MATERIAL AND METHODS This multicenter, retrospective study included 1013 women at ≥28 gestational weeks with a vertex singleton gestation and 1 prior low-transverse cesarean from January 2017 to December 2017 in 11 public tertiary hospitals within 7 provinces of China. Two multivariable logistic regression models were developed: (1) at a first-trimester visit and (2) at the pre-labor admission to hospital. The models were evaluated with the area under the receiver operating characteristic curve (AUC) and internally validated using k-fold cross-validation. The pre-labor model was calibrated and a graphic nomogram and clinical impact curve were created. RESULTS A total of 87.3% (884/1013) of women had successful VBAC, and 12.7% (129/1013) underwent unplanned cesarean delivery after a failed trial of labor. The AUC of the first-trimester model was 0.661 (95% confidence interval [CI]: 0.61-0.712), which increased to 0.758 (95% CI: 0.715-0.801) in the pre-labor model. The pre-labor model showed good internal validity, with AUC 0.743 (95% CI: 0.694-0.785), and was well calibrated. CONCLUSIONS VBAC provides women the chance to experience a vaginal delivery. Using a pre-labor model to predict successful VBAC is feasible and may help choose mode of birth and contribute to a reduction in cesarean delivery rate.

Percutaneous closure of the left atrial appendage: The value of real time 3D transesophageal echocardiography and the intraoperative change in the size of the left atrial appendage.

OBJECTIVE: The aim of this study was to investigate the value of real time three-dimensional transesophageal echocardiography (RT3DTEE) in percutaneous closure of the left atrial appendage (LAAC). In addition, this study also explored the change in the size of the left atrial appendage (LAA) from 24 hours before the operation to just before implantation during the operation. METHODS AND RESULTS: In a retrospective study, 32 patients underwent two-dimensional transesophageal echocardiography (2DTEE) and RT3DTEE 24 hours prior to operation and during operation. The maximal LAA orifice diameter (by 2DTEE, 22.7 ± 2.7 vs 24.6 ± 2.2 mm, P < 0.01; by RT3DTEE, 24.2 ± 2.9 vs 25.8 ± 2.7 mm, P < 0.01), the maximal landing zone diameter (by 2DTEE, 19.0 ± 2.8 vs 20.4 ± 2.8 mm, P < 0.01; by RT3DTEE, 20.4 ± 2.7 vs 22.6 ± 3.0 mm, P < 0.01), and the maximal depth diameter (by 2DTEE, 25.2 ± 3.2 vs 26.5 ± 3.0 mm, P < 0.01; by RT3DTEE, 26.4 ± 3.2 vs 27.5 ± 3.7 mm, P < 0.01) all increased significantly during the operation. The highest correlation (R) between the maximal landing zone diameter and the compressed occluder diameter was determined for RT3DTEE measurements during the operation (R = 0.90), whereas the landing zone diameter (R = 0.80) measured by 2DTEE was less correlated. In addition, our study showed that RT3DTEE was of great value in discriminating the LAA orifice shape, allowing differentiation of the LAA morphology and identification of the number of LAA lobes. CONCLUSIONS: A certain amount of intravenous rehydration just before and during operation increased the LAA size significantly. The measurements by RT3DTEE showed a closer correlation to LAA occluder size than those by 2DTEE. The LAA displayed by RT3DTEE was more visible than that by 2DTEE.

Obesity induced caveolin-1 impairs osteogenesis via activating mitophagy and inhibiting Sirt1 signaling.

Obesity has become a major global health problem and the effect on bone formation has received increasing attention. However, the interaction between obesity and bone metabolism is complex and still not fully understood. Here, we show that caveolin-1 (Cav1), a membrane scaffold protein involved in regulating a variety of cellular processes, plays a key regulatory role as a bridge connecting obesity and bone metabolism. High-fat diet (HFD)-induced obese C57BL/6J mouse displayed a significant increase in Cav1 expression and lower osteogenic activity; In vitro treatment of osteoblastic MC3T3-E1 cells with 1 mM free fatty acids (FFA) significantly promoted Cav1 expression and PINK1/Parkin regulated mitophagy, but inhibited the expression of osteogenic marker genes. Conversely, reduced expression of the Cav1 gene prevented these effects. Both endogenous oxidative stress and Sirt1 pathway were also significantly reduced after Cav1 knockdown in FFA-treated cells. Finally, Cav1-Sirt1 docking and co-immunoprecipitation results showed that Cav1 interacted with Sirt1 and FFA enhanced the interaction. Taken together, these results suggest that obesity impairs bone development and formation through up-regulation of the Cav1 gene, which lead to inhibition of Sirt1/FOXO1 and Sirt1/PGC-1α signaling pathways through interacting with Sirt1 molecule, and an increase of mitophagy level.

Development, validation, and clinical utility of a risk prediction model for recurrent preeclampsia.

OBJECTIVES: We aim to establish a predictive model for recurrent preeclampsia. METHODS: A retrospective review of medical records from three hospitals between 2010 and 2021 was conducted. The study included women who had two consecutive singleton deliveries at the same hospital, with the first delivery complicated by preeclampsia. A multivariable logistic regression model was constructed using a training cohort, and subsequently cross-validated and tested using an independent cohort. The model's performance was assessed in terms of discrimination and calibration, and its clinical utility was evaluated using decision curve analysis (DCA). RESULTS: Among 296 405 deliveries, 694 women met the inclusion criteria, with 151 (21.8%) experiencing recurrent preeclampsia. The predictive model incorporated 10 risk factors from previous preeclampsia, including gestational weeks with elevated blood pressure, gestational diabetes mellitus (GDM), pericardial effusion, heart failure, limb edema, serum creatinine, white blood cell count, low platelet counts within one week before delivery, SBP on the first postpartum day, and postpartum antihypertensive use. Additionally, one risk factor from the index pregnancy was included, which was antihypertensive use before 20 weeks. The model demonstrated better discrimination, calibration, and a net benefit across a wide range of recurrent preeclampsia risk thresholds. Furthermore, the model has been translated into a clinical risk calculator, enabling clinicians to calculate individualized risks of recurrent preeclampsia. CONCLUSION: Our study demonstrates that a predictive tool utilizing routine clinical and laboratory factors can accurately estimate the risk of recurrent preeclampsia. This predictive model has the potential to facilitate shared decision-making by providing personalized and risk-stratified care.

Comparing the severity of second preeclampsia with first preeclampsia: a multicenter retrospective longitudinal cohort study.

OBJECTIVE: Compare the clinical severity of second preeclampsia with the first preeclampsia. METHODS: This retrospective longitudinal cohort study was conducted in three teaching hospitals in Guangzhou, where there were a total of 296 405 deliveries between 2010 and 2021. Two consecutive singleton deliveries complicated with preeclampsia were included. Clinical features, laboratory results within 1 week before delivery, and maternal and neonatal outcomes of both deliveries were collected. Univariate analyses were made using paired Wilcoxon tests and McNemar tests. Multivariable logistic regression and generalized linear models were performed to assess the association of adverse maternal and neonatal outcomes with second preeclampsia. RESULTS: A total of 151 women were included in the study. The mean maternal age was 28 and 33 years for the first and second deliveries, respectively. The proportion of preventive acetylsalicylic acid use was 4.6% for the first delivery and 15.2% for the second delivery. No significant differences were observed in terms of blood pressure on admission, gestational weeks of admission and delivery, application of perinatal antihypertensive agents, rates of preterm delivery, and severe features between the two occurrences. However, the rates of heart disease, edema, and admission to the ICU were lower, and hospital stays were shorter in the second preeclampsia compared with the first preeclampsia. Sensitivity analysis conducted among women who did not use preventive acetylsalicylic acid yielded similar results. After adjusting for potential confounding variables, the occurrence of second preeclampsia was associated with significantly decreased risks of heart disease, edema, complications, and admission to the NICU, with odds ratios ranging between 0.157 and 0.336. CONCLUSION: Contrary to expectations, the second preeclampsia did not exhibit worse manifestations or outcomes to the first occurrence. In fact, some clinical features and outcomes appeared to be better in the second preeclampsia.

KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.

Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Downregulation of fatty acid oxidation led by Hilpda increases G2/M arrest/delay-induced kidney fibrosis.

Hypoxia-regulated proximal tubular epithelial cells (PTCs) G2/M phase arrest/delay was involved in production of renal tubulointerstitial fibrosis (TIF). TIF is a common pathological manifestation of progression in patients with chronic kidney disease (CKD), and is often accompanied by lipid accumulation in renal tubules. However, cause-effect relationship between hypoxia-inducible lipid droplet-associated protein (Hilpda), lipid accumulation, G2/M phase arrest/delay and TIF remains unclear. Here we found that overexpression of Hilpda downregulated adipose triglyceride lipase (ATGL) promoted triglyceride overload in the form of lipid accumulation, leading to defective fatty acid ß-oxidation (FAO), ATP depletion in a human PTC cell line (HK-2) under hypoxia and in mice kidney tissue treated with unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI). Hilpda-induced lipid accumulation caused mitochondrial dysfunction, enhanced expression of profibrogenic factors TGF-ß1, α-SMA and Collagen I elevation, and reduced expression of G2/M phase-associated gene CDK1, as well as increased CyclinB1/D1 ratio, resulted in G2/M phase arrest/delay and profibrogenic phenotypes. Hilpda deficiency in HK-2 cell and kidney of mice with UUO had sustained expression of ATGL and CDK1 and reduced expression of TGF-ß1, Collagen I and CyclinB1/D1 ratio, resulting in the amelioration of lipid accumulation and G2/M arrest/delay and subsequent TIF. Expression of Hilpda correlated with lipid accumulation, was positively associated with tubulointerstitial fibrosis in tissue samples from patients with CKD. Our findings suggest that Hilpda deranges fatty acid metabolism in PTCs, which leads to G2/M phase arrest/delay and upregulation of profibrogenic factors, and consequently promote TIF which possibly underlie pathogenesis of CKD.

Oxytocin treatments or activation of the paraventricular nucleus-the shell of nucleus accumbens pathway reduce adverse effects of chronic social defeat stress on emotional and social behaviors in Mandarin voles.

Chronic social stress can cause psychological disease. Although oxytocin (OT) has been showed to modulate effects of chronic social defeat stress (CSDS) on emotional and social behaviors, however, how OT circuits mediate effects of CSDS on emotional and social abnormalities remains unclear. Here, we found that repeated intraperitoneal OT administration in the process of CSDS buffered adverse effects of CSDS on emotional and social behaviors in mandarin voles (Microtus mandarinus) of both sexes except no effect on depression-like behavior of males. Repeated OT treatments during CSDS prevented decrease of oxytocin receptors in nucleus accumbens (NAc) in females, but produced no effects on males. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools, we determined that the activation of the paraventricular nucleus (PVN)-the shell of NAc (NAcs) projections before social defeat during CSDS process significantly prevented the increase of the anxiety-like behaviors and social avoidance induced by CSDS in both sexes, and reversed the depressive-like behaviors induced by CSDS only in females. Besides, optogenetic activation of PVN-NAcs projections after CSDS reduced anxiety-like behaviors and increased levels of sociality. Collectively, we suggest that PVN-NAcs projections modulate emotional and social behaviors during or after the process of CSDS sex-specifically, although AAV viruses did not specifically infect OT neurons. These findings offer potential targets for preventing or treating emotional and social disorders induced by chronic stress.

Association between short inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery.

OBJECTIVE: To explore the association between inter-pregnancy intervals and placenta previa and placenta accreta spectrum among women who had prior cesarean deliveries with respect to maternal age at first cesarean delivery. METHODS: This retrospective study included clinical data from 9981 singleton pregnant women with a history of cesarean delivery at 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. The study population was divided into four groups (<2, 2-5, 5-10, ≥10 years of the interval) according to the inter-pregnancy interval. The rate of placenta previa and placenta accreta spectrum among the four groups was compared, and multivariate logistic regression was used to analyze the relationship between inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery. RESULTS: Compared to women aged 30-34 years old at first cesarean delivery, the risk of placenta previa (aRR, 1.48; 95% CI, 1.16-1.88) and placenta accreta spectrum (aRR, 1.74; 95% CI, 1.28-2.35) were higher among women aged 18-24. Multivariate regression results showed that women at 18-24 with <2 years intervals exhibited a 5.05-fold increased risk for placenta previa compared with those with 2-5-year intervals (aRR, 5.05; 95% CI, 1.13-22.51). In addition, women aged 18-24 with less than 2 years intervals had an 8.44 times greater risk of developing PAS than women aged 30-34 with 2 to 5 years intervals (aRR, 8.44; 95% CI, 1.82-39.26). CONCLUSIONS: The findings of this study suggested that short inter-pregnancy intervals were associated with increased risks for placenta previa, and placenta accreta spectrum for women under 25 years at first cesarean delivery, which may be partly attributed to obstetrical outcomes.