The effect of skin diffusion kinetics of isopropyl ester permeation enhancers on drug permeation: Role of lateral spread and penetration characteristics.

The purpose of present work was to study the effects of permeation enhancers' two kinetic behaviors of simultaneous lateral diffusion and vertical penetration in the skin on its enhancing effect. The skin diffusion kinetics of isopropyl ester permeation enhancers were characterized by the innovative concentric tape peeling study and Raman imaging, which were quantitatively assessed through innovative parameters, namely, lateral-to-vertical penetration amount (CL-V) and lateral-to-vertical penetration distance (DL-V). The enhancement effect of permeation enhancers on drug flurbiprofen (FLU) was assessed by in vitro skin permeation tests, which were confirmed by transdermal water loss and skin resistance study. The relationship between kinetic parameters of permeation enhancers and permeation parameters of FLU was carried out by correlation analysis. The molecular mechanisms of effect of skin diffusion kinetics of permeation enhancers on drug permeation were characterized by molecular docking, modulated-temperature differential scanning calorimetry (MTDSC), Raman spectra, solid-state NMR and molecular dynamic simulation. The results indicated skin diffusion kinetics of short-chain (C8-C12) isopropyl ester permeation enhancers were governed by vertical penetration, while long-chain (C14-C18) ones were characterized by lateral spread. Quadratic correlation between CL-V and enhancement ratio of permeation-retention ratio of FLU (ERQ/R) (R2 = 0.95), DL-V and enhancement ratio of permeation area (ERA) of FLU (R2 = 0.98) indicating that varied skin diffusion kinetics of permeation enhancers directly influenced the barrier function of stratum corneum (SC) and further enhancing drug permeation. In terms of molecular mechanism, long-chain isopropyl ester enhancers had good miscibility with SC, leading to their high CL-V and DL-V, and causing strong interaction strength with SC and resulting in weaker skin barrier function for drug permeation. In summary, in comparison to short-chain isopropyl ester enhancers that relied on penetration, long-chain ones that depended on lateral spread exhibited greater enhancement efficacy, which guided the application of enhancers in transdermal formulations.

The exploration of surgery and survival prediction in patients with peritoneal metastasis from gastric adenocarcinoma based on the SEER database.

Background: As one of the most common diseases in terms of cancer-related mortality worldwide, gastric adenocarcinoma (GA) frequently develops peritoneal metastases (PMs) in advanced stages. Systemic therapy or optimal supportive care are recommended for advanced GA; however, patients frequently develop drug resistance. Surgical resection is not recommended for stage IV patients, and there have been some controversies regarding the role of it in GA patients with PMs. The aim of the study was to preliminarily evaluate the possible effect of surgical treatments on patients with only PMs from GA. Methods: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2000-2022). A propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables on comparisons. Then Cox proportional hazard regression, Kaplan-Meier analysis, and log-rank test were performed to assess the efficacy of surgical treatment in patients with PMs from GA. Results: A total of 399 patients diagnosed with PMs from GA were enrolled for our analysis, of which, 180 (45.1%) patients did not receive surgery and 219 (54.9%) patients received surgery. Multivariate Cox regression analysis before PSM indicated higher rates of overall survival (OS) outcome for patients who had received surgery [hazard ratio (HR) =0.4342, 95% confidence interval (CI): 0.3283-0.5742, P<0.001]. After PSM, a total of 172 patients were enrolled, with 86 in each group. Multivariate Cox analysis showed that surgery was the independent factor reflecting patients' survival (HR =0.4382, 95% CI: 0.3037-0.6324, P<0.001). Subgroup survival analysis revealed that surgery may bring advantages to patients with grades I-IV, stages T1-T4, stage N0, and tumor size less than 71 mm (P<0.05). We also found that the OS of chemotherapy patients who had undergone surgery was better than that of chemotherapy patients who had not undergone surgery (P<0.01). Conclusions: Based on the SEER database, surgery has better OS for patients only with PMs from GA. Patients without lymph node metastasis and those who received chemotherapy before may benefit from surgery. These specific groups of patients may have surgery as an option to improve the prognosis.

A Novel Cholesterol Metabolism-Related lncRNA Signature Predicts the Prognosis of Patients with Hepatocellular Carcinoma and Their Response to Immunotherapy.

BACKGROUND: The survival rate of hepatocellular carcinoma (HCC) is low and the prognosis is poor. Metabolic reprogramming is still an emerging hallmark of cancer, and reprogramming of cholesterol metabolism plays a crucial action in tumor pathogenesis. Increasing evidence suggests that cholesterol metabolism affects the cell proliferation, invasion, migration, and resistance to chemotherapy of HCC. To date, no long noncoding RNA (lncRNA) signature associated with cholesterol metabolism has been developed to predict the outcome of patients with HCC. METHODS: The RNA-seq data as well as the prognostic and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We conducted univariate and multivariate analyses to assess cholesterol metabolism-related lncRNAs correlated with the prognosis of patients with HCC in order to construct a prognostic signature. Functional differences between low- and high-risk groups were investigated using genomic enrichment analysis (GSEA). Kaplan-Meier (KM) curves were applied to explore the overall survival (OS) of the low- and high-risk groups. Single-sample genomic enrichment analysis (ssGSEA) was applied to investigate the association between this predictive signature and immune function. We subsequently examined how this signature relates to treatment response in HCC patients. RESULTS: A prognostic signature comprising six lncRNAs related to cholesterol metabolism was constructed (AC124798.1, AL031985.3, AC103760.1, NRAV, WAC-AS1 and AC022613.1). We found that low-risk groups showed a better prognosis than high-risk groups. In HCC patients, the cholesterol metabolism-related lncRNA signature may be served as an independent prognostic factor. Cholesterol metabolism-related lncRNA signature had higher diagnostic efficiency compared to clinicopathologic variables. After stratifying patients according to different clinicopathological variables, patients with low-risk had a longer OS compared with high-risk patients. The ssGSEA demonstrated that this signature was closely related to the immune status of HCC patients. GSEA analysis demonstrated that immune- and tumor-related pathways were predominantly enriched in the high-risk group. High-risk patients were more responsive to immune checkpoint inhibitors (ICIs) and conventional chemotherapeutic agents. CONCLUSIONS: This cholesterol metabolism-related lncRNA signature can predict the prognosis of HCC patients and guide the clinical management of HCC patients, including immunotherapy.

Predictive value of procollagen c-protease enhancer protein on the prognosis of glioma patients.

Procollagen c-protease enhancer protein (PCOLCE) performs an essential action in improving the recreation of procollagen c-protease and promoting the reconstruction of extracellular matrix. High PCOLCE expression was associated with a negative prognosis of stomach cancer, ovarian cancer, and osteosarcoma. The goal of this work is to investigate the function of PCOLCE in glioma. Multiple bioinformatics techniques have been employed to investigate the roles of PCOLCE in glioma, consisting of the correlation between PCOLCE and prognosis, immune checkpoints, immune cell infiltrates, and tumor microenvironment (TME). The gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the potential function of PCOLCE in glioma. PCOLCE was found to be increased in glioma. We revealed that PCOLCE was a potential prognostic factor and related to tumor grade. Up-regulated PCOLCE was related to poor prognosis in lower-grade glioma (LGG), glioblastoma multiforme (GBM), and recurrent glioma. PCOLCE was correlated with immune cell infiltration, particularly B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LGG, and DCs infiltration in GBM. PCOLCE was co-expressed with many genes related to the immune and the immune checkpoint. In addition, glioma patients with low expression of PCOLCE had a higher response to the immunological checkpoint blockade (ICB). Additionally, PCOLCE may exert its roles via several immune-related biological processes or pathways, such as leukocyte migration, activation of T cells, adaptive immune response, neutrophil-mediated immunity, NF-κB, and TNF signaling pathways. In conclusion, PCOLCE may be a new immune-related gene and regulate tumor development through immunological pathways.

Heme oxygenase-1 is an equid alphaherpesvirus 8 replication restriction host protein and suppresses viral replication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathway.

Equid alphaherpesvirus 8 (EqHV-8) is one of the most economically important viruses that is known to cause severe respiratory disease, abortion, and neurological syndromes in equines. However, no effective vaccines or therapeutic agents are available to control EqHV-8 infection. Heme oxygenase-1 (HO-1) is an antioxidant defense enzyme that displays significant cytoprotective effects against different viral infections. However, the literature on the function of HO-1 during EqHV-8 infection is little. We explored the effects of HO-1 on EqHV-8 infection and revealed its potential mechanisms. Our results demonstrated that HO-1 induced by cobalt-protoporphyrin (CoPP) or HO-1 overexpression inhibited EqHV-8 replication in susceptible cells. In contrast, HO-1 inhibitor (zinc protoporphyria) or siRNA targeting HO-1 reversed the anti-EqHV-8 activity. Furthermore, biliverdin, a metabolic product of HO-1, mediated the anti-EqHV-8 effect of HO-1 via both the protein kinase C (PKC)ß/extracellular signal-regulated kinase (ERK)1/ERK2 and nitric oxide (NO)-dependent cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathways. In addition, CoPP protected the mice by reducing the EqHV-8 infection in the lungs. Altogether, these results indicated that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.IMPORTANCEEqHV-8 infections have threatened continuously donkey and horse industry worldwide, which induces huge economic losses every year. However, no effective vaccination strategies or drug against EqHV-8 infection until now. Our present study found that one host protien HO-1 restrict EqHV-8 replication in vitro and in vivo. Furthermore, we demonstrate that HO-1 and its metabolite biliverdin suppress EqHV-8 relication via the PKCß/ERK1/ERK2 and NO/cGMP/PKG pathways. Hence, we believe that HO-1 can be developed as a promising therapeutic strategy to control EqHV-8 infection.

Enhancing squat movement classification performance with a gated long-short term memory with transformer network model.

Bodyweight squat is one of the basic sports training exercises. Automatic classification of aberrant squat movements can guide safe and effective bodyweight squat exercise in sports training. This study presents a novel gated long-short term memory with transformer network (GLTN) model for the classification of bodyweight squat movements. Twenty-two healthy young male participants were involved in an experimental study, where they were instructed to perform bodyweight squat in nine different movement patterns, including one acceptable movement defined according to the National Strength and Conditioning Association and eight aberrant movements. Data were acquired from four customised inertial measurement units placed at the thorax, waist, right thigh, and right shank, with a sampling frequency of 200 Hz. The results show that compared to state-of-art deep learning models, our model enhances squat movement classification performance with 96.34% accuracy, 96.31% precision, 96.45% recall, and 96.32% F-score. The proposed model provides a feasible wearable solution to monitoring aberrant squat movements that can facilitate performance and injury risk assessment during sports training. However, this model should not serve as a one-size-fits-all solution, and coaches and practitioners should consider individual's specific needs and training goals when using it.

Exploring flatfeet morphology in children aged 6-12 years: relationships with body mass and body height through footprints and three-dimensional measurements.

The aim of the study was to determine the relationship between flatfoot morphology and body mass and height in children aged 6-12 years. A total of 6471 Chinese children (mean age 9.0 ± 1.9 years, 41% female) were assessed for foot morphometry, body height, and body mass index. Foot morphology, including foot length, width, girth, arch height, hallux valgus angle, and rearfoot valgus angle, was measured using a 3D laser scanner. Flatfoot evaluations were conducted using the Sztriter-Godunov index (KY) from footprints. All measurements were analyzed by age and sex using the mean values of the left and right sides. Comparisons were performed between flatfoot groups, between body mass index (BMI) groups, and between body height groups. The study revealed a significant decrease in the incidence of bipedal flatfoot with age (p < 0.001), whereas the prevalence of obesity remained consistent (p > 0.05). Bipedal flatfoot was associated with distinct morphological changes, including lower arches, reduced instep height, diminished ankle heights and a greater rearfoot valgus angle (p < 0.05). When comparing the BMI groups, overweight children had larger and thicker feet (p < 0.05), but no differences were found in arch height and ankle height (p > 0.05). When comparing the body height groups, short-statured children had a shorter feet girth, shorter arches, and shorter ankle height (p < 0.05), but no differences were found in the rearfoot valgus angle (p > 0.05). CONCLUSION: The main characteristics of flat feet include lower arches and instep heights and ankle heights but higher rearfoot valgus angles. In general, overweight children's feet do not have the common features of flat feet. In contrast, short children had similar features of flatfoot except for rearfoot valgus. Assessment of posture, such as rearfoot valgus, can be critical in identifying children with flat feet. WHAT IS KNOWN: • The morphology of children's feet is associated with body growth, but the relationship between flatfeet and body mass and height remains controversial. WHAT IS NEW: • Three-dimensional foot measurement shows that body mass is generally not associated with flatfeet, while short children have lower arches but no rearfoot valgus.

Higher pre-pregnancy body mass index was associated with adverse pregnancy and perinatal outcomes in women with polycystic ovary syndrome after a freeze-all strategy: A historical cohort study.

INTRODUCTION: Previous studies have demonstrated that abnormal body mass index (BMI) is associated with adverse pregnancy outcomes in frozen-thawed embryo transfer cycles. However, the relationship between BMI and pregnancy and perinatal outcomes in patients with polycystic ovary syndrome (PCOS) remains unclear. Furthermore, whether a diagnosis of PCOS could result in adverse pregnancy and perinatal outcomes in women with different BMIs remains unknown. MATERIAL AND METHODS: A historical cohort study included 1667 women with PCOS and 12 256 women without PCOS after a freeze-all policy between January 2016 and December 2020. The outcomes encompassed both pregnancy and perinatal outcomes. Multivariate logistic regression analysis and restricted cubic spline models were performed to eliminate confounding factors when investigating the relationship between BMI and different outcomes. RESULTS: After controlling for covariates, pregnancy outcomes were comparable between underweight women with PCOS and normal weight women with PCOS. However, overweight patients had a lower clinical pregnancy rate and an overall live birth rate. Furthermore, patients with obesity had a lower rate of multiple pregnancies but a higher rate of biochemical pregnancy than in the normal BMI group. Additionally, the restricted cubic spline models showed that as maternal BMI increased to 32 kg/m2, the clinical pregnancy rate and live birth rate after blastocyst transfer decreased, but the risks of preterm birth, gestational diabetes mellitus, macrosomia, large-for-gestational age (LGA) and very LGA increased in patients with PCOS after a freeze-all strategy. Moreover, a diagnosis of PCOS resulted in a higher clinical pregnancy rate and live birth rate and a higher risk of small-for-gestational age in the normal weight group. However, women with PCOS in the overweight group exhibited higher risks of very preterm birth and gestational diabetes mellitus compared with women without PCOS. CONCLUSIONS: This study showed that a higher BMI had a detrimental impact on the pregnancy and perinatal outcomes of PCOS patients undergoing a freeze-all strategy. However, it was only statistically significant in the overweight group. A diagnosis of PCOS had a higher clinical pregnancy rate and live birth rate in normal weight women but higher risks of perinatal complications in normal weight and overweight women.

A Low-Cost Instrumented Shoe System for Gait Phase Detection Based on Foot Plantar Pressure Data.

This paper presents a novel low-cost and fully-portable instrumented shoe system for gait phase detection. The instrumented shoe consists of 174 independent sensing units constructed based on an off-the-shelf force-sensitive film known as the Velostat conductive copolymer. A zero potential method was implemented to address the crosstalk effect among the matrix-formed sensing arrays. A customized algorithm for gait event and phase detection was developed to estimate stance sub-phases including initial contact, flat foot, and push off. Experiments were carried out to evaluate the performance of the proposed instrumented shoe system in gait phase detection for both straight-line walking and turning walking. The results showed that the mean absolute time differences between the estimated phases by the proposed instrumented shoe system and the reference measurement ranged from 45 to 58 ms during straight-line walking and from 51 to 77 ms during turning walking, which were comparable to the state of art.Clinical and Translational Impact Statement-By allowing convenient gait monitoring in home healthcare settings, the proposed system enables extensive ADL data collection and facilitates developing effective treatment and rehabilitation strategies for patients with movement disorders.

Development of a low-cost and user-friendly system to create personalized human digital twin.

Creating a digital twin has enormous potential in biomedical engineering. However, it is also technically challenging. No existing system can allow people who don't have the art-and-design background to create their own digital twin. To fill this gap, this study proposes a low-cost wearable system and a user-friendly framework for creating personalized digital twins with a fast speed and high fidelity. The personalized human digital twin can capture synchronized facial expressions, gaze direction, and whole-body movements for real-time rendering. The system simplifies the complex process of creating digital humans, and allows for the creation of data-driven characters without specialized skills.Clinical Relevance- This system can be used to help doctors keep track record of the patient's health status in a more visual and realistic way, supporting them in making more accurate clinical decisions, and facilitating a more detailed medical intervention.

Surgical Continuum Manipulator Control Using Multiagent Team Deep Q Learning.

Continuum manipulator has shown great potential in surgical applications. The flexibility of the continuum manipulator helps it achieve many complicated surgeries, such as neurosurgery, vascular surgery, abdominal surgery, etc. In this paper, we propose a Team Deep Q learning framework (TDQN) to control a 2-DoF surgical continuum manipulator with four cables, where two cables in a pair form one agent. During the learning process, each agent shares state and reward information with the other one, which namely is centralized learning. Using the shared information, TDQN shows better targeting accuracy than multiagent deep Q learning (MADQN) by verifying on a 2-DoF cable-driven surgical continuum manipulator. The root mean square error during tracking with and without disturbance are 0.82mm and 0.16mm respectively using TDQN, whereas 1.52mm and 0.98mm using MADQN respectively.Clinical Relevance-The proposed TDQN shows a promising future in improving control accuracy under disturbance and maneuverability in robotic-assisted endoscopic surgery.

Training Induced Improvement on Human Perception of the Force Feedback Provided by A Soft Robotic Glove.

Creating haptic interface by glove-based wearable robotic system has become an increasingly interested topic in the area of human robotic interaction. Many force feedback gloves are constructed based on soft actuators. However, the recent development of haptic and force feedback technology mainly focused on the advancement of the actuating components and mechanism, and innovation of the force feedback rendering algorithms. It seems that another important part of this human-robot-interaction loop, i.e. the human factors, were understudied. Here, this study focused on the learning effect in haptic perception. We designed a pneumatic muscle-based force feedback robotic glove which can provide customized force feedback to the dorsal surface of each finger. An experiment was carried out with a specifically training procedure and evaluation on the force feedback perceptions. The results show that practice-induced improvement can be achieved by this training, allowing people have a better perception of the force feedback provided by this glove.

Cobalt Protoporphyrin Blocks EqHV-8 Infection via IFN-α/ß Production.

Equid alphaherpesvirus type 8 (EqHV-8) is the causative agent of severe respiratory disease, abortions, and neurological syndromes in equines and has resulted in huge economic losses to the donkey industry. Currently, there exist no therapeutic molecules for controlling EqHV-8 infection. We evaluated the potential antiviral activity of cobalt protoporphyrin (CoPP) against EqHV-8 infection. Our results demonstrated that CoPP inhibited EqHV-8 infection in susceptible cells and mouse models. Furthermore, CoPP blocked the replication of EqHV-8 via HO-1 (heme oxygenase-1) mediated type I interferon (IFN) response. In conclusion, our data suggested that CoPP could serve as a novel potential molecule to develop an effective therapeutic strategy for EqHV-8 prevention and control.

Young women were associated with higher risk of hypertensive disorders of pregnancy and cesarean section from hormone replaced cycles in frozen-thawed embryo transfer: a retrospective study of 5316 singleton deliveries.

Background: The utilization of frozen-thawed embryo transfer (FET) cycles has been linked to heightened risks of adverse perinatal outcomes. However, the potential association between adverse perinatal outcomes and distinct endometrial preparation regimens remains unclear. Therefore, we aim to investigate the maternal and neonatal outcomes after hormone replacement treatment (HRT) cycles, natural cycles (NC) and HRT cycles with pretreatment using GnRHa (HRT + GnRHa) for ovulatory women undergoing FET cycles. Methods: A large sample retrospective cohort study was carried out from 2016 to 2020. The data included a total of 5316 women who had singleton deliveries undergoing FET cycles and which were divided into three groups based on different endometrial preparation protocols: 4399 patients in HRT groups, 621 in GnRHa+HRT groups, 296 in NC groups. The outcomes consisted of maternal outcomes (cesarean section, hypertensive disorders of pregnancy (HDP), placenta previa, gestational diabetes mellitus (GDM));and neonatal outcomes (preterm birth, newborn birthweight, low birthweight, small for gestational age (SGA), macrosomia, large for gestational age (LGA), fetal malformation). Results: After adjusting for a series of confounding variables, we found an increased risk of HDP (aOR=3.362; 95%CI, 1.059-10.675) and cesarean section (aOR=1.838; 95%CI, 1.333-2.535) in HRT cycles compared with NC, especially for ovulatory women under 35 years old. However, in all three groups, newborn birth weight was not significantly different. Meanwhile, perinatal outcomes did not differ significantly in terms of perinatal outcomes in HRT +GnRHa cycles compared with HRT cycles solely. Conclusion: During FET cycles, singletons from HRT were related to higher risks of HDP and cesarean section, particularly for young women. GnRHa pretreatment didn't bring any benefit to perinatal outcomes compared with HRT cycles alone. Therefore, the natural cycle may be a more appropriate and safer option for young ovulatory women.

Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration.

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, the mechanism underlying this type of cell migration remains unclear. Here we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo epithelial-mesenchymal transition-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-hijacked RhoA signaling significantly alters cellular morphology and rearranges the actin cytoskeleton involving the depolymerization of robust actin stress fibers, leading-edge protrusion formation, and the rear-edge recontraction, which coordinates VACV-induced cell migration. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.

ATP6V1F is a novel prognostic biomarker and potential immunotherapy target for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the deadliest malignancies worldwide, with late detection, ineffective treatment and poor overall survival. Immunotherapy, including immune checkpoint inhibitor (ICI) therapy, holds great potential for treatment of HCC. Although some patients respond well to ICIs, many fail to obtain a significant benefit. It is therefore of great interest to find appropriate markers to stratify patient responses to immunotherapy and to explore suitable targets for modulating the TME and immune cell infiltration. ATP6V1F encodes a constituent of vacuolar ATPase (V-ATPase). V-ATPase-mediated acidification of organelles is required for intracellular processes such as zymogen activation, receptor-mediated endocytosis, protein sorting and synaptic vesicle proton gradient generation. In this study, we confirmed for the first time that ATP6V1F is overexpressed in HCC and related to poor prognosis in these patients. We identified that overexpression of ATP6V1F is associated with infiltration of some immune cells and expression of several immune checkpoints. Furthermore, we explored the possible mechanisms of action of ATP6V1F. Finally, we conducted in vitro experiments, including wound healing, Transwell invasion, and apoptosis assays, to verify that ATP6V1F promotes development of HCC by promoting migration and invasion and inhibiting apoptosis of HCC cells. Our findings will contribute to providing precise immunotherapy to patients with HCC.

Nomogram for predicting the risk of preterm delivery after IVF/ICSI treatment: an analysis of 11513 singleton births.

Background: There is a higher risk of preterm delivery (PTD) in singleton live births conceived after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) compared with spontaneously conceived pregnancies. The objective of our study was to build a predictive nomogram model to suggest the possibility of PTD in singleton pregnancies after IVF/ICSI treatment. Method: 11513 IVF/ICSI cycles with singleton live births were enrolled retrospectively. These cycles were randomly allocated into a training group (80%) and a validation group (20%). We used the multivariate logistics regression analysis to determine prognostic factors for PTD in the training group. A nomogram based on the above factors was further established for predicting PTD. Receiver operating characteristic curves (ROC), areas under the ROC curves (AUC), concordance index (C-index), and calibration plots were analyzed for assessing the performance of this nomogram in the training and validation group. Results: There were fourteen risk factors significantly related to PTD in IVF/ICSI singleton live births, including maternal body mass index (BMI) > 24 kg/m2, smoking, uterine factors, cervical factors, ovulatory factors, double embryo transferred (DET), blastocyst transfer, FET, vanishing twin syndrome (VTS), obstetric complications (placenta previa, placenta abruption, hypertensive of pregnancies, and premature rupture of membrane), and a male fetus. These factors were further incorporated to construct a nomogram prediction model. The AUC, C-index, and calibration curves indicated that this nomogram exhibited fair performance and good calibration. Conclusions: We found that the occurrence of PTD increased when women with obesity, smoking, uterine factors, cervical factors, ovulatory factors, DET, VTS, and obstetric complications, and a male fetus. Furthermore, a nomogram was constructed based on the above factors and it might have great value for clinic use.

Cumulative live birth rates and birth outcomes after IVF/ICSI treatment cycles in young POSEIDON patients: A real-world study.

Objective: The aim of this study was to describe the cumulative live birth rates (CLBRs) of young women with or without low prognosis according to the POSEIDON criteria after IVF/ICSI cycles and to investigate whether the diagnosis of low prognosis increases the risk of abnormal birth outcomes. Design: Retrospective study. Setting: A single reproductive medicine center. Population: From January 2016 to October 2020, there were 17,893 patients (<35 years) involved. After screening, 4,105 women were included in POSEIDON group 1, 1,375 women were included in POSEIDON group 3, and 11,876 women were defined as non-POSEIDON. Interventions: Baseline serum AMH level was measured on the D2-D3 of menstrual cycle before IVF/ICSI treatment. Main outcome measures: Cumulative live birth rate (CLBR), birth outcomes. Results: After four stimulation cycles, the CLBRs in POSEIDON group 1, POSEIDON group 3, and non-POSEIDON group reached 67.9% (95% CI, 66.5%-69.3%), 51.9% (95% CI, 49.2%-54.5%), and 79.6% (95% CI, 78.9%-80.3%), respectively. There was no difference in gestational age, preterm delivery, cesarean delivery, and low birth weight infants between the three groups, but macrosomia was significantly higher in non-POSEIDON group, after adjusting for maternal age and BMI. Conclusions: The POSEIDON group shows lower CLBRs than the non-POSEIDON group in young women, while the risk of abnormal birth outcomes in the POSEIDON group will not increase.

PCSK9, a novel immune and ferroptosis related gene in abdominal aortic aneurysm neck.

The gene expression profile of abdominal aortic aneurysm (AAA) neck is not fully understood. The etiology of AAA is considered to be related to atherosclerosis and the inflammatory response, involving congenital, genetic, metabolic, and other factors. The level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to those of cholesterol, oxidized low-density lipoprotein, and triglycerides. PCSK9 inhibitors have significant effects on lowering LDL-cholesterol, reversing atherosclerotic plaques, and reducing the risk of cardiovascular events and have been approved by several lipid-lowering guidelines. This work was aimed to investigate the potential role of PCSK9 in the neck of AAA. We extracted the expression dataset (GSE47472) containing 14 AAA patients and 8 donors and single-cell RNAseq (scRNA-seq) data (GSE164678) of CaCl2-induced (AAA) samples from the Gene Expression Omnibus dataset. Through bioinformatics methods, we found that PCSK9 was up-regulated in the proximal neck of human AAA. In AAA, PCSK9 was mainly expressed in fibroblasts. Additionally, immune check-point PDCD1LG2 was also expressed higher in AAA neck than donor, while CTLA4, PDCD1, and SIGLEC15 were down-regulated in AAA neck. The expression of PCSK was correlated with PDCD1LG2, LAG3, and CTLA4 in AAA neck. Additionally, some ferroptosis-related genes were also down-regulated in AAA neck. PCSK9 was also correlated with ferroptosis-related genes in AAA neck. In conclusion, PCSK9 was highly expressed in AAA neck, and may exert its role through interacting with immune check-points and ferroptosis-related genes.