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.

Microglial activation contributes to cognitive impairments in rotenone-induced mouse Parkinson's disease model.

BACKGROUND: Cognitive decline occurs frequently in Parkinson's disease (PD), which greatly decreases the quality of life of patients. However, the mechanisms remain to be investigated. Neuroinflammation mediated by overactivated microglia is a common pathological feature in multiple neurological disorders, including PD. This study is designed to explore the role of microglia in cognitive deficits by using a rotenone-induced mouse PD model. METHODS: To evaluate the role of microglia in rotenone-induced cognitive deficits, PLX3397, an inhibitor of colony-stimulating factor 1 receptor, and minocycline, a widely used antibiotic, were used to deplete or inactivate microglia, respectively. Cognitive performance of mice among groups was detected by Morris water maze, objective recognition, and passive avoidance tests. Neurodegeneration, synaptic loss, α-synuclein phosphorylation, glial activation, and apoptosis were determined by immunohistochemistry and Western blot or immunofluorescence staining. The gene expression of inflammatory factors and lipid peroxidation were further explored by using RT-PCR and ELISA kits, respectively. RESULTS: Rotenone dose-dependently induced cognitive deficits in mice by showing decreased performance of rotenone-treated mice in the novel objective recognition, passive avoidance, and Morris water maze compared with that of vehicle controls. Rotenone-induced cognitive decline was associated with neurodegeneration, synaptic loss, and Ser129-phosphorylation of α-synuclein and microglial activation in the hippocampal and cortical regions of mice. A time course experiment revealed that rotenone-induced microglial activation preceded neurodegeneration. Interestingly, microglial depletion by PLX3397 or inactivation by minocycline significantly reduced neuronal damage and α-synuclein pathology as well as improved cognitive performance in rotenone-injected mice. Mechanistically, PLX3397 and minocycline attenuated rotenone-induced astroglial activation and production of cytotoxic factors in mice. Reduced lipid peroxidation was also observed in mice treated with combined PLX3397 or minocycline and rotenonee compared with rotenone alone group. Finally, microglial depletion or inactivation was found to mitigate rotenone-induced neuronal apoptosis. CONCLUSIONS: Taken together, our findings suggested that microglial activation contributes to cognitive impairments in a rotenone-induced mouse PD model via neuroinflammation, oxidative stress, and apoptosis, providing novel insight into the immunopathogensis of cognitive deficits in PD.

SARS-CoV-2 infection in animals: Patterns, transmission routes, and drivers.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is more widespread in animals than previously thought, and it may be able to infect a wider range of domestic and wild species. To effectively control the spread of the virus and protect animal health, it is crucial to understand the cross-species transmission mechanisms and risk factors of SARS-CoV-2. This article collects published literature on SARS-CoV-2 in animals and examines the distribution, transmission routes, biophysical, and anthropogenic drivers of infected animals. The reported cases of infection in animals are mainly concentrated in South America, North America, and Europe, and species affected include lions, white-tailed deer, pangolins, minks, and cats. Biophysical factors influencing infection of animals with SARS-CoV-2 include environmental determinants, high-risk landscapes, air quality, and susceptibility of different animal species, while anthropogenic factors comprise human behavior, intensive livestock farming, animal markets, and land management. Due to current research gaps and surveillance capacity shortcomings, future mitigation strategies need to be designed from a One Health perspective, with research focused on key regions with significant data gaps in Asia and Africa to understand the drivers, pathways, and spatiotemporal dynamics of interspecies transmission.

Walking or jogging during pregnancy increases the success rate of vaginal birth after cesarean delivery: A multicenter, retrospective cohort study.

OBJECTIVE: Exercise during pregnancy has been proven to reduce the risk of cesarean delivery. However, few studies have examined the relationship between walking or jogging during pregnancy and the success rate of vaginal birth after cesarean delivery (VBAC). This multicenter, retrospective cohort study aimed to determine the association between walking or jogging during pregnancy and the success rate of VBAC in women who underwent a trial of labor after cesarean delivery. METHODS: The study was conducted between January 2018 and December 2019 in Foshan, China. Univariate and multivariable analyses were performed on demographic and obstetric data collected from the electronic record system. RESULTS: Of 1080 women included in the final analysis, 80.4% underwent VBAC. In the multivariable analysis, women who walked or jogged ≥200 min/week during pregnancy had a higher likelihood of successful VBAC than women who did not exercise, after adjusting for two sets of confounders: Model 1: Adjusted odds ratio (OR), 1.74 (95% confidence interval [CI], 1.06-2.85) and model 2: Adjusted OR, 1.83 (95% CI, 1.09-3.06). CONCLUSIONS: Walking or jogging ≥200 min/week during pregnancy significantly reduces the risk of cesarean delivery among women who undergo a trial of labor after cesarean delivery.

Prediction of vaginal birth after cesarean in China.

OBJECTIVE: This study aimed to develop and validate a prediction model of vaginal birth after cesarean delivery (VBAC) in China. METHODS: A nomogram for effective prediction of VBAC of singleton, cephalic and one previous low-transverse cesarean section deliveries was created by comparing the combinations of ultrasonographic and non-ultrasonographic factors from five hospitals between 2018 and 2019. RESULTS: A total of 1066 women were included. Of the women who underwent trial of labor after cesarean (TOLAC), 854 (80.1%) had a VBAC. Ultrasound factors included reached a higher area under the curve (AUC) combined with non-ultrasonographic factors. Of the three ultrasonographic factors analyzed, the best predictive factor for successful TOLAC was fetal abdominal circumference. A nomogram was generated with eight validated factors, including maternal age, gestational week, height, previous vaginal delivery, Bishop score, dilatation of the cervix at the time of admission, body mass index at delivery, and fetal abdominal circumference by ultrasound. The trained and validated AUC were 0.719 (95% confident interval 0.674-0.764) and 0.774 (95% confident interval 0.712-0.837), respectively. CONCLUSION: Our VBAC nomogram based on obstetric factors and fetal abdominal circumference obtained by ultrasound could be used to counsel women who are considering TOLAC.

Inflammatory myofibroblastic tumor of the submandibular gland Harboring MSN-ALK gene fusion: A case report and literature review.

Inflammatory myofibroblastic tumors (IMTs) are rare lesions with distinct clinical, pathological, and molecular characteristics. IMTs typically arise in the abdominal soft tissues, including the mesentery, omentum, and retroperitoneum, followed by the lungs and mediastinum, and usually affect both children and young adults. Herein, we present a rare case of an IMT in the submandibular gland of a 47-year-old male patient. Microscopically, the tumor displayed an infiltrative growth pattern with diffuse glandular tissue destruction. Their backgrounds revealed characteristic spindles and inflammatory cells. Immunohistochemistry revealed positivity for anaplastic lymphoma kinase (ALK), smooth muscle actin, and calponin in neoplastic cells. The inflammatory cells and some neoplastic cells were positive for CD68. In contrast, negative staining for cytokeratin, desmin, and CD30 was observed. Furthermore, fluorescence in situ hybridization revealed ALK gene rearrangements, and next-generation sequencing detected a moesin (MSN)-ALK gene fusion. This case highlights a rare and unique occurrence of IMT originating from the submandibular gland, which exhibited an MSN-ALK gene fusion.

Chaperone-mediated autophagy promotes breast cancer angiogenesis via regulation of aerobic glycolysis.

Evidence shows that chaperone-mediated autophagy (CMA) is involved in cancer cell pathogenesis and progression. However, the potential role of CMA in breast cancer angiogenesis remains unknown. We first manipulated CMA activity by knockdown and overexpressing of lysosome-associated membrane protein type 2A (LAMP2A) in MDA-MB-231, MDA-MB-436, T47D and MCF7 cells. We found that the tube formation, migration and proliferation abilities of human umbilical vein endothelial cells (HUVECs) were inhibited after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A knockdown. While the above changes were promoted after cocultured with tumor-conditioned medium from breast cancer cells of LAMP2A overexpression. Moreover, we found that CMA could promote VEGFA expression in breast cancer cells and in xenograft model through upregulating lactate production. Finally, we found that lactate regulation in breast cancer cells is hexokinase 2 (HK2) dependent, and knockdown of HK2 can significantly reduce the ability of CMA-mediated tube formation capacity of HUVECs. Collectively, these results indicate that CMA could promote breast cancer angiogenesis via regulation of HK2-dependent aerobic glycolysis, which may serve as an attractive target for breast cancer therapies.

Clinical Efficacy and Safety of Lacosamide as an Adjunctive Treatment in Adults With Refractory Epilepsy.

Background: Lacosamide (LCM), a novel AED (antiepileptic drug), was used as an adjunctive treatment in patients with partial-onset seizures or without secondary generalization. However, no meta-analysis was performed to evaluate the efficacy of LCM as an adjunctive treatment in post-marketing clinical studies. Aims: To assess the safety and efficacy of LCM as an adjunctive treatment in adults with refractory epilepsy, a systematic review and meta-analysis of randomized controlled trials (RCTs) and real-world studies were performed. Methods: All studies were identified from electronic databases. Both RCTs and observational prospective studies were included. Primary outcomes included responder rate, adverse effects (AEs) and withdraw rate. The pooled rates (PR) with their corresponding 95% confidence intervals (CI) were calculated. Publication bias was assessed with Begg's or Egger's tests. Results: Total 16 studies (3,191 patients) including 5 RCTs and 11 real-word studies were enrolled. The pooled 50% responder rate and seizure-free rate were 48% (95% CI: 0.42, 0.54) and 9% (95% CI: 0.06, 0.11) in all studies, respectively. Subgroup analysis showed that the pooled 50% responder rate were 53% (95% CI: 0.44, 0.62) from observational studies and 38% (95% CI: 0.35, 0.42) from RCTs, respectively; the pooled seizure-free rate were 13% (95% CI: 0.09, 0.18) from observational studies and 4% (95% CI: 0.06, 0.11) from RCTs, respectively. Similar incidence of AEs were reported in real-world studies (0.57, 95% CI: 0.43, 0.72) and RCTs (0.59, 95% CI: 0.42-0.76). Finally, a total of 13% (95%CI: 0.09, 0.16) and 13% (95% CI: 0.08, 0.16) of all patients prescribed with LCM was withdrawn in RCTs and real-world studies, respectively, due to the occurrence of AEs. Furthermore, similar to the 50% responder rate, seizure-free rate, incidence of AEs and withdraw rate were reported at 6-month or at least 12-month of LCM adjunction. Publication bias was not detected in these studies. Conclusions: Our results revealed that LCM adjunctive therapy even with long-term treatment was efficacious and well tolerated in adults with refractory epilepsy.

Pre-exposure to 50 Hz-electromagnetic fields enhanced the antiproliferative efficacy of 5-fluorouracil in breast cancer MCF-7 cells.

Resistance to 5-fluorouracil (5-FU) and its induced immune suppression have prevented its extensive application in the clinical treatment of breast cancer. In this study, the combined effect of 50 Hz-EMFs and 5-FU in the treatment of breast cancer was explored. MCF-7 and MCF10A cells were pre-exposed to 50 Hz-EMFs for 0, 2, 4, 8 and 12 h and then treated with different concentrations of 5-FU for 24 h; cell viability was analyzed by MTT assay and flow cytometry. After pre-exposure to 50 Hz-EMFs for 12 h, apoptosis and cell cycle distribution in MCF-7 and MCF10A cells were detected via flow cytometry and DNA synthesis was measured by EdU incorporation assay. Apoptosis-related and cell cycle-related gene and protein expression levels were monitored by qPCR and western blotting. Pre-exposure to 50 Hz-EMFs for 12 h enhanced the antiproliferative effect of 5-FU in breast cancer cell line MCF-7 in a dose-dependent manner but not in normal human breast epithelial cell line MCF10A. Exposure to 50 Hz-EMFs had no effect on apoptosis and P53 expression of MCF-7 and MCF10A cells, whereas it promoted DNA synthesis, induced entry of MCF-7 cells into the S phase of cell cycle, and upregulated the expression levels of cell cycle-related proteins Cyclin D1 and Cyclin E. Considering the pharmacological mechanisms of 5-FU in specifically disrupting DNA synthesis, this enhanced inhibitory effect might have resulted from the specific sensitivity of MCF7 cells in active S phase to 5-FU. Our findings demonstrate the enhanced cytotoxic activity of 5-FU on MCF7 cells through promoting entry into the S phase of the cell cycle via exposure to 50 Hz-EMFs, which provides a novel method of cancer treatment based on the combinatorial use of 50 Hz-EMFs and chemotherapy.

Effect of 5-caffeoylquinic acid on the NF-κB signaling pathway, peroxisome proliferator-activated receptor gamma 2, and macrophage infiltration in high-fat diet-fed Sprague-Dawley rat adipose tissue.

Obesity, considered as a consequence of overnutrition, sustains a low-degree inflammatory state and results in insulin-resistance and type 2 diabetes. Here, we investigated the anti-inflammatory effects of 5-caffeoylquinic acid (5-CQA) in high-fat diet-induced obese rats. Serum interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-α), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) levels were determined. Expression of genes related to TG metabolism, macrophage biomarkers, and inflammation was assessed by real-time PCR. Protein expression of NF-κB, PPARγ2, and phosphorylated IκBα was evaluated by western blotting, and the histology of adipose tissue was examined. Supplementation of the rat diet with 5-CQA reduced obesity development, macrophage infiltration, and steatosis. Additionally, 5-CQA decreased the expression of NF-κB and downstream inflammatory cytokines, but increased the expression of PPARγ2, in a dose-dependent manner. Thus, 5-CQA improved obesity and obesity-related metabolic disturbances via PPARγ2 and the NF-κB signaling pathway.