ß-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization.

Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of ß-mangostin, a xanthone derivative obtained from the mangosteen fruit. This research investigated the role of ß-mangostin on microglia in the glioma microenvironment and evaluated the efficacy of ß-mangostin combined with anti-PD-1 antibody (αPD-1) in glioma-bearing mice. The results showed that, ß-mangostin attenuated M2 polarization in BV2 cells and promoted M1-related interleukin (IL)-1ß and IL-6 secretion, thereby inhibiting glioma invasion. In addition, ß-mangostin improved the anti-glioma effects of αPD-1 and increased CD8+T cell and M1-type microglia infiltration. Mechanistically, ß-mangostin bound to the stimulator of interferon genes (STING) protein, which is crucial for the anti-tumor innate immune response, and promoted STING phosphorylation in microglia, both in vivo and in vitro. These results provide insights into its mode of action and supporting further investigation into ß-mangostin as a therapeutic agent.

Sex differences in dorsolateral prefrontal cortical and superior colliculus activities support the impact of alcohol use severity and sleep deficiency on two-back memory.

Background: Working memory refers to a process of temporary storage and manipulation of information to support planning, decision-making, and action. Frequently comorbid alcohol misuse and sleep deficiency have both been associated with working memory deficits. However, how alcohol misuse and sleep deficiency interact to impact working memory remains unclear. In this study, we aim to investigate the neural processes inter-relating alcohol misuse, sleep deficiency and working memory. Methods: We curated the Human Connectome Project (HCP) dataset and investigated the neural correlation of working memory in link with alcohol use severity and sleep deficiency in 991 young adults (521 women). The two were indexed by the first principal component (PC1) of principal component analysis of all drinking metrics and Pittsburgh Sleep Quality Index (PSQI) score, respectively. We processed the imaging data with published routines and evaluated the results with a corrected threshold. We used path model to characterize the inter-relationship between the clinical, behavioral, and neural measures, and explored sex differences in the findings. Results: In whole-brain regression, we identified ß estimates of dorsolateral prefrontal cortex response (DLPFC ß) to 2- vs. 0-back in correlation with PC1. The DLPFC showed higher activation in positive correlation with PC1 across men and women (r=0.16, P<0.001). Path analyses showed the model PC1 → DLPFC ß â†’ differences in reaction time (2- minus 0-back; RT2-0) of correct trials → differences in critical success index (2- minus 0-back; CSI2-0) with the best fit. In women alone, in addition to the DLPFC, a cluster in the superior colliculus (SC) showed a significant negative correlation with the PSQI score (r=-0.23, P<0.001), and the path model showed the inter-relationship of PC1, PSQI score, DLPFC and SC ß's, and CSI2-0 in women. Conclusions: Alcohol misuse may involve higher DLPFC activation in functional compensation, whereas, in women only, sleep deficiency affects 2-back memory by depressing SC activity. In women only, path model suggests inter-related impact of drinking severity and sleep deficiency on 2-back memory. These findings suggest potential sex differences in the impact of drinking and sleep problems on working memory that need to be further investigated.

High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life.

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions. Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics. Design, Setting, and Participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023. Exposures: Protein aptamers, measured at study V3 and V5. Main Outcomes and Measures: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty. Results: A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF. Conclusions and Relevance: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

Clinical analysis of uterine parameters evaluated by preoperative magnetic resonance imaging in patients treated by hysteroscopic approach with previous cesarean scar defect-related abnormal uterine bleeding: a retrospective cohort study.

Background: As the cesarean delivery rate continues to rise globally, the treatment of previous cesarean scar defects (PCSD) remains challenging. This study aimed to analyze the variables that may influence the clinical cure rate of patients with PCSD-related abnormal uterine bleeding (AUB) as determined by preoperative magnetic resonance imaging (MRI) following hysteroscopic therapy. Methods: Women who underwent hysteroscopic surgery for PCSD-related AUB at the Gynecology Department of Third Xiangya Hospital of Central South University from 2018 to 2022 were recruited to this retrospective cohort investigation. A total of 147 patients were enrolled in this study and underwent follow-up over 6 months. The significance of clinical characteristics linked to the clinical cure rate of AUB was examined by logistic regression. Results: There were 64 clinically cured (43.5%) and 83 non-clinically cured (56.5%) patients in the study. There were no significant differences in the age, menstrual duration, gravidity, parity, number of cesarean sections, time since the previous cesarean section, uterus position, width, depth, and thickness of the remaining muscle layer of the defect by MRI T2-weighted images (T2WI) before hysteroscopic surgery between the 2 groups. MRI T2WI of the myometrial thickness adjacent to the defect [P=0.038, odds ratio (OR) =2.095, 95% confidence interval (CI): 1.047-4.261] and the distance from the defect to the external cervical os (P=0.021, OR =2.254, 95% CI: 1.136-4.540) before hysteroscopic surgery are risk factors for the clinical cure rate. Conclusions: The myometrial thickness adjacent to the defect and the distance from the defect to the external cervical os in preoperative MRI are risk factors for clinical cure rate in patients with PCSD-related AUB after hysteroscopic treatment, which is helpful for evaluating the prognosis of disease.

Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis.

BACKGROUND: Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms. OBJECTIVES: The aim of this study was to discover novel biomarkers with potentially causal associations with AS. METHODS: We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over 6 years and with AV calcification with the use of cardiac computed tomography, replicated analysis in an independent sample, performed Mendelian randomization, and evaluated gene expression in explanted human AV tissue. RESULTS: Fifty-two proteins cross-sectionally were associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3. Among 3,413 participants in the Cardiovascular Health Study, 6 of those proteins were significantly associated with adjudicated moderate or severe AS, including matrix metalloproteinase 12 (MMP12), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), and growth differentiation factor-15. MMP12 was also associated with greater increase in AVmax over 6 years, greater degree of AV calcification, and greater expression in calcific compared with normal or fibrotic AV tissue. C1QTNF1 had consistent potential causal effects on both AS and AVmax according to Mendelian randomization analysis. CONCLUSIONS: These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression.

Feasibility of Two-Screw Anterior Fixation for Odontoid Fractures in a Chinese Population: A Morphometric Study Based on Computed Tomography.

Background: To evaluate the feasibility of treating odontoid fractures in the Chinese population with two cortical screws based on computed tomography (CT) scans and describe a new measurement strategy to guide screw insertion in treating these fractures. Methods: A retrospective review of cervical computed tomographic scans of 128 patients (aged 18-76 years; men, 55 [43.0%]) was performed. The minimum external transverse diameter (METD), minimum external anteroposterior diameter (MEAD), maximum screw length (MSL), and screw projection back angle (SPBA) of the odontoid process were measured on coronal and sagittal CT images. Results: The mean values of METD and MEAD were 10.0 ± 1.1 mm and 12.0 ± 1.0 mm, respectively, in men and 9.2 ± 1.0 mm and 11.0 ± 1.0 mm, respectively, in women. Both measurements were significantly higher in men (p < 0.001). In total, 87 individuals (68%) had METD > 9.0 mm that could accommodate two 3.5-mm cortical screws. The mean MSL value and SPBA range were 34.4 ± 2.9 mm and 13.5°-24.2°, respectively, with no statistically significant difference between men and women. Conclusions: The insertion of two 3.5-mm cortical screws was possible for anterior fixation of odontoid fractures in 87 patients (68%) in our study, and there was a statistically significant difference between men and women.

Dual Responsive Magnetic Drug Delivery Nanomicelles with Tumor Targeting for Enhanced Cancer Chemo/Magnetothermal Synergistic Therapy.

Introduction: Stimulus-responsive nanocarrier systems are promising in cancer treatment. They improve drug stability and facilitate controlled drug release. However, single-responsive nanocarriers still face insufficient tumor targeting and low efficacy. Methods: In this study, we synthesized folate-modified DSPE-PEOz nanomicelles with PEG chains and loaded them with magnetic iron particles and doxorubicin (DOX). Folic acid (FA) was employed as a ligand to target cancer cells actively. The nanomicelles are biocompatible and acid-sensitive drug carriers. Magnetic field-responsive nanoparticles enable moderately controlled magnetothermal therapy of tumors regardless of tumor location. The pH/magnetic field dual-responsive nanomicelles shed their PEG layer in response to tumor tissue acidity and react to magnetic fields through magnetothermal effects. Results: In vitro and in vivo experiments demonstrated that the nanomicelles could efficiently target cancer cells, release drugs in response to pH changes, and enhance drug uptake through magnetothermal effects. Discussion: The dual-responsive magnetic nanomicelles are expected to enhance the anti-cancer efficacy of chemo/magnetothermal synergistic therapy.

Association between albumin-to-globulin ratio and the risk of overall survival in advanced non-small cell lung cancer patients with anlotinib treatment: a retrospective cohort study.

OBJECTIVE: Researches about the association between serum albumin-to-globulin ratio (AGR) and the prognosis of lung cancer are limited. We aimed to investigate the relationship between AGR and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) treated with anlotinib. METHODS: A retrospective cohort study was conducted on 196 advanced NSCLC patients with anlotinib treatment between June 1, 2018 and June 1, 2021. The exposure was AGR, calculated by baseline serum albumin / (serum total protein - serum albumin). The outcome was OS, defined as the period from the date of initial treatment with anlotinib to death or the last follow-up. The univariate and multivariate linear regression models and generalized additive models (GAM) were used to analyze the relationship between AGR and OS. The Kaplan-Meier method was used to analyze the OS. RESULTS: After adjusting for potential confounders, a non-linear relationship was observed between AGR and OS, which had an inflection point of 1.24. The hazard ratio and the confidence intervals on the left and the right sides of the inflection point were 13.05 (0.52 to 327.64) and 0.20 (0.07 to 0.57), respectively. It suggested that AGR was positively associated with OS when AGR was larger than 1.24, for every 1 unit increase in AGR, the risk of death lowered approximately by 80%. CONCLUSIONS: The relationship between AGR and the OS for advanced NSCLC patients with anlotinib is non-linear. AGR level is an independent protective factor for OS in advanced NSCLC patients who received anlotinib therapy.

Artificial intelligence diagnosis of intrauterine adhesion by 3D ultrasound imaging: a prospective study.

Background: There were a very large number of intrauterine adhesion (IUA) patients. As improving the classification of three-dimensional transvaginal ultrasound (3D-TVUS) of IUA or non-IUA images remains a clinical challenge and is needed to avoid inappropriate surgery. Our study aimed to evaluate deep learning as a method to classify 3D-TVUS of IUA or non-IUA images taken with panoramic technology. Methods: After meeting an inclusion/exclusion criteria, a total of 4,401 patients were selected for this study. This included 2,803 IUA patients and 1,598 non-IUA patients. IUA was confirmed by hysteroscopy, and each patient underwent one 3D-TVUS examination. Four well-known convolutional neural network (CNN) architectures were selected to classify the IUA images: Visual Geometry Group16 (VGG16), InceptionV3, ResNet50, and ResNet101. We used these pretrained CNNs on ImageNet by applying both TensorFlow and PyTorch. All 3D-TVUS images were normalized and mixed together. We split the data set into a training set, validation set, and test set. The performance of our classification model was evaluated according to sensitivity, precision, F1-score, and accuracy, which were determined by equations that used true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) numbers. Results: The overall performances of VGG16, InceptionV3, ResNet50, and ResNet101 were better in PyTorch as opposed to TensorFlow. Through PyTorch, the best CNN model was InceptionV3 with its performance measured as 94.2% sensitivity, 99.4% precision, 96.8% F1-score, and 97.3% accuracy. The area under the curve (AUC) results of VGG16, InceptionV3, ResNet50, and ResNet101 were 0.959, 0.999, 0.997, and 0.999, respectively. PyTorch also successfully transferred information from the source to the target domain where we were able to use another center's data as an external test data set. No overfitting that could have adversely affected the classification accuracy occurred. Finally, we successfully established a webpage to diagnose IUA based on the 3D-TVUS images. Conclusions: Deep learning can assist in the binary classification of 3D-TVUS images to diagnose IUA. This study lays the foundation for future research into the integration of deep learning and blockchain technology.

Redundant targeting signals of the apicoplast-resident protein TgMnmA in Toxoplasma gondii involve trans-organellar function.

The apicoplast, which is the result of secondary endosymbiosis, is a distinctive subcellular organelle and a crucial therapeutic target for apicomplexan parasites. The majority of apicoplast-resident proteins are encoded by the nuclear genome and target the apicoplast via bipartite targeting signals consisting of a signal peptide and a transit peptide. The properties and functions of these peptides are poorly understood, which hinders the identification of apicoplast proteins and the study for plastid evolution. Here, the targeting signals of the recently discovered apicoplast tRNA thiouridylase TgMnmA of Toxoplasma gondii were analyzed. Our data using a reporter (the enhanced green fluorescent protein) fused with individual fragments containing various numbers of its N-terminal amino acids unequivocally revealed that the first 28 amino acids of TgMnmA functioned as a signal peptide for cellular secretion. The N-terminal 150 amino acids were sufficient to direct the fusion protein to the apicoplast, whereas its deletion caused the fusion protein to be localized to the mitochondrion. Our data further demonstrated that the apicoplast, rhoptry, and mitochondrion shared similar targeting signals, indicating that the apicoplast localization peptide was trans-organellar in function. In addition, the apicoplast localization peptide was important for the healthy proliferation of tachyzoites. In conclusion, the targeting signals of the nucleus-encoded apicoplast-targeted protein TgMnmA have been mapped out and the importance of this localization peptide has been elucidated in the current study.

Changes in biochemical indicators in scientific load training in tennis players / Alterações dos indicadores bioquímicos no treinamento científico de carga em jogadores de tênis / Cambios de los indicadores bioquímicos en el entrenamiento científico con carga en tenistas

ABSTRACT Introduction The level of physical training of tennis players directly affects the performance of competitive and athletic ability of tennis players. The uniqueness of tennis is that it places high demands on athletes' skills, tactics, and fitness. This requires constant monitoring of their biomarkers for real-time control of athletes' health. Objective Study the impact of scientific methods of load training on tennis players and their changes in biomarkers. Methods This paper tests tennis players' immune, physiological, and biochemical indices after load training. Results After training, tennis players' immune, physiological, and biochemical indices show evident differences. Conclusion Scientific load training helps improve tennis players' physiological and biochemical indices and immune function. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O nível de treinamento físico dos jogadores de tênis afeta diretamente o desempenho da capacidade competitiva e atlética dos tenistas. A singularidade do tênis é que ele coloca altas exigências nas habilidades, táticas e aptidão física dos atletas. Isto exige um monitoramento constante de seus biomarcadores para controle em tempo real na saúda dos atletas. Objetivo Estudar o impacto dos métodos científicos de treino com carga em jogadores de tênis e suas alterações nos biomarcadores. Métodos Este artigo testa os índices imunes dos tenistas e os índices fisiológicos e bioquímicos relacionados após o treinamento com carga. Resultados Após o treinamento, os índices imunológicos e os índices fisiológicos e bioquímicos correspondentes dos jogadores de tênis apresentam diferenças evidentes em relação aos anteriores. Conclusão O treinamento científico de carga ajuda a melhorar os índices fisiológicos e bioquímicos e a função imunológica dos jogadores de tênis. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El nivel de entrenamiento físico de los tenistas afecta directamente al rendimiento de la capacidad competitiva y atlética de los tenistas. La singularidad del tenis es que exige mucho a los deportistas en cuanto a habilidades, táctica y forma física. Esto requiere un seguimiento constante de sus biomarcadores para controlar en tiempo real la salud de los deportistas. Objetivo Estudiar el impacto de los métodos científicos de entrenamiento de carga en los tenistas y sus cambios en los biomarcadores. Métodos En este trabajo se analizan los índices inmunológicos de los tenistas y los índices fisiológicos y bioquímicos relacionados tras el entrenamiento con carga. Resultados Tras el entrenamiento, los índices inmunológicos y los correspondientes índices fisiológicos y bioquímicos de los tenistas muestran diferencias evidentes con respecto a los anteriores. Conclusión El entrenamiento con carga científica ayuda a mejorar los índices fisiológicos y bioquímicos y la función inmunitaria de los tenistas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

In vitro fertilization and embryo transfer may improve live birth rate for patients with intrauterine adhesions after hysteroscopic adhesiolysis. / 体外受精-èƒšèƒŽç§»æ¤æœ¯æœ‰åŠ©äºŽæé«˜å®«è ”ç²˜è¿žåˆ†ç¦»æœ¯åŽæ‚£è€ çš„æ´»äº§çŽ‡.

OBJECTIVES: The prevalence of intrauterine adhesion (IUA) increased gradually, which seriously affected female reproductive health and fertility. This study aims to analyze the clinical features of pre-, intra-, and post hysteroscopic adhesiolysis (HA) and to identify the main risk factors for non-live birth and other factors affecting pregnancy outcome in patients with IUA. METHODS: A total of 486 IUA patients with reproductive needs, who underwent HA in the third Xiangya Hospital of Central South University from January 2017 to May 2018, were retrospectively included. The follow-up period was 2-3 years after operation. Univariate analysis and multivariate logistic regression analysis were used to explore the relationship between clinical features and live birth rate in patients with IUA. Pre-operative clinical indicators included age, gravidity, parity, abortion, IUA recurrence, menstrual patterns, and disease course. Intraoperative clinical features assessed in the last operation were uterine cavity length, IUA appearance, IUA area, number of visible uterine cornua, number of visible tubal ostia, and American Fertility Society (AFS) scores. The relationship between clinical indicators and postoperative live birth rate was investigated by univariate analysis and multivariate logistic regression analysis. Pregnancy pattern was the main variable. RESULTS: Among the 486 IUA patients included in this study, there were 256 (52.67%) live births and 230 (47.33%) non-live births. Univariate analysis and multivariate logistic regression showed that the live birth rate of in vitro fertilization and embryo transfer (IVF-ET) after HA was higher than that of spontaneous pregnancy (OR=0.557, 95% CI 0.361 to 0.861, P=0.008). When the bilaterally fallopian tube ostia were invisible in the last operation (OR=0.322, 95% CI 0.104 to 0.997, P=0.049), patients were more likely to have live birth. The older the patient was, the lower the live birth rate was (OR=1.081, 95% CI 1.034 to 1.131, P<0.001). The live birth rate would be low when the last AFS score was moderate (OR=2.973, 95% CI to 1.541 to 5.738, P<0.010). CONCLUSIONS: Based on the outcome of the first pregnancy after HA, IUA patients' pregnancy patterns, age, number of visible tubal ostia, and AFS scores noted by a second-look hysteroscopy, are the factors influencing the prognosis for the live birth rate in IUA patients. IVF-ET may improve live birth rate for patients with IUA after HA.

Dynamic risk prediction models for different subtypes of hypertensive disorders in pregnancy.

Background: Hypertensive disorders in pregnancy (HDP) are diseases that coexist with pregnancy and hypertension. The pathogenesis of this disease is complex, and different physiological and pathological states can develop different subtypes of HDP. Objective: To investigate the predictive effects of different variable selection and modeling methods on four HDP subtypes: gestational hypertension, early-onset preeclampsia, late-onset preeclampsia, and chronic hypertension complicated with preeclampsia. Methods: This research was a retrospective study of pregnant women who attended antenatal care and labored at Beijing Maternity Hospital, Beijing Haidian District Maternal and Child Health Hospital, and Peking University People's Hospital. We extracted maternal demographic data and clinical characteristics for risk factor analysis and included gestational week as a parameter in this study. Finally, we developed a dynamic prediction model for HDP subtypes by nonlinear regression, support vector machine, stepwise regression, and Lasso regression methods. Results: The AUCs of the Lasso regression dynamic prediction model for each subtype were 0.910, 0.962, 0.859, and 0.955, respectively. The AUC of the Lasso regression dynamic prediction model was higher than those of the other three prediction models. The accuracy of the Lasso regression dynamic prediction model was above 85%, and the highest was close to 92%. For the four subgroups, the Lasso regression dynamic prediction model had the best comprehensive performance in clinical application. The placental growth factor was tested significant (P < 0.05) only in the stepwise regression dynamic prediction model for early-onset preeclampsia. Conclusion: The Lasso regression dynamic prediction model could accurately predict the risk of four HDP subtypes, which provided the appropriate guidance and basis for targeted prevention of adverse outcomes and improved clinical care.

Dynamic prediction model of fetal growth restriction based on support vector machine and logistic regression algorithm.

Background: This study analyzed the influencing factors of fetal growth restriction (FGR), and selected epidemiological and fetal parameters as risk factors for FGR. Objective: To establish a dynamic prediction model of FGR. Methods: This study used two methods, support vector machine (SVM) and multivariate logistic regression, to establish the prediction model of FGR at different gestational weeks. Results: At 20-24 weeks and 25-29 weeks of gestation, the effect of the multivariate Logistic method on model prediction was better. At 30-34 weeks of gestation, the prediction effect of FGR model using the SVM method is better. The ROC curve area was above 85%. Conclusions: The dynamic prediction model of FGR based on SVM and logistic regression is helpful to improve the sensitivity of FGR in pregnant women during prenatal screening. The establishment of prediction models at different gestational ages can effectively predict whether the fetus has FGR, and significantly improve the clinical treatment effect.

PARP inhibitors diminish DNA damage repair for the enhancement of tumor photodynamic therapy.

Pancreatic cancer is a lethal malignancy and only around 4% of patients will live 5 years post-diagnosis. Photodynamic therapy (PDT) is a promising strategy for treating malignant tumors because of its high selectivity. Through the colocalization of light, oxygen and photosensitizer, a large number of reactive oxygen species (ROS) are generated under excitation at a specific wavelength of a laser, which can induce DNA damage and destroy cancer cells. However, the repair mechanism of cell will repair part of the damaged DNA, which could reduce the efficiency of PDT. The poly (ADP-Ribose) polymerase (PARP) plays a wide and multifaceted role in the cellular response to DNA damage, with growing evidence for participation in multiple pathways of DNA damage repair and genome maintenance. Cells require PARP to resolve single-strand DNA breaks (SSBs) induced by chemotherapy agents. Its inhibition is thought to result in the accumulation of damage in DNA, which may eventually lead to cell death. The combination therapy of PDT and PARP inhibitors may benefit patients. In this study, we design and synthesize a zeolitic imidazolate framework-8 (ZIF-8) to co-deliver DNA damaging agent Chlorin e6 (Ce6) and PARP inhibitor Olaparib (Ola). Ce6 and Ola demonstrate strong synergistic actions, providing a novel approach for the treatment of pancreatic cancer.

Correlative study of preoperative three-dimensional transvaginal ultrasound findings and ongoing pregnancy/live birth in patients with intrauterine adhesions following hysteroscopic adhesiolysis: a retrospective study.

Background: Three-dimensional transvaginal ultrasound (3D-TVUS) has recently been adopted in the gynecological sciences as it provides an accurate illustration of adhesions and the extent of cavity damage, and hence, can be used as an essential tool for the prognosis of intrauterine adhesions (IUA). This study aims to demonstrate whether preoperative 3D-TVUS features are relevant to ongoing pregnancy and live births in patients with IUA following hysteroscopic adhesiolysis (HA). Methods: From February 22, 2018, to October 31, 2018, a total of 401 patients with moderate to severe IUA and underwent HA were retrospectively enrolled. Preoperative 3D-TVUS diagnosed data and the patients' basic information were collected, and patients were followed up over 2 years after HA for reproductive outcomes. The correlation between each imaging variable and ongoing pregnancy or live birth was analyzed by binary logistic regression. Results: Among the 401 patients, 143 had live births, 41 patients had abortions, and 217 patients were infertile. Thick endometrium was found to be favorable for ongoing pregnancy (ongoing pregnancy group =5.4±1.95 mm, no-ongoing pregnancy group =4.7±2.24 mm, P=0.0095) and live birth (live birth group=5.6±1.92 mm, no-live birth group =4.7±2.20 mm, P=0.0029). Scar contraction was not conducive for pregnancy, while the lower segmentation was not a risk factor for ongoing pregnancy (P=0.0003). It also was a risk factor for ongoing pregnancy (P<0.0001) and live birth (P<0.0001) when the segmentation of the endometrial absence was mainly in the upper and middle segments of the uterine cavity. The area under the curves (AUCs) of the prediction model for ongoing pregnancy and live birth were 0.9116 and 0.8751, respectively, based on the meaningful variables above combined with other clinical characteristics. Conclusions: Preoperative 3D-TVUS features have a close correlation with ongoing pregnancy and live births in patients with IUA following HA, and can be applied for predicting ongoing pregnancy and live births in IUA patients post-HA.

A case of pulmonary histoplasmosis treated with voriconazole.

Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. The lungs are the most common site of infection, especially in patients with immune deficiency. We report a case of 62-year-old male patient presented with cough for 3 months and had been taking immunosuppressive drugs for 10 years after heart transplantation. Chest CT scan showed multiple pulmonary nodules. Lung tissue biopsy specimen culture suggested fungal infection, and Histoplasma capsulatum was confirmed by next-generation sequencing (NGS) detection. The patient was diagnosed with pulmonary histoplasmosis. After administration of voriconazole for 46 days, the symptom of cough was markedly relieved and the lesions were partly absorbed. After 13 months of treatment, the lesions completely disappeared, and no significant side-effect of voriconazole was observed. To our knowledge, report of voriconazole as the treatment of histoplasmosis is rare, especially in non-endemic areas. Moreover, this case enriches our experience in the adjustment between immunosuppressive and antifungal agents in treating histoplasmosis.

Influence of catalysts on bio-oil yield and quality: a review.

The catalytic production of bio-oil can potentially solve the impending fossil fuel depletion crisis. Two practical problems related to bio-oil are the yield and quality, which are determined by the catalyst. Until recently, little work has focused on the relationship between biomass, catalyst, yield, and quality. To cover this deficiency, this work reviews the influence of metal oxides and zeolites on the yields and qualities of bio-oil derived from woody, herbaceous, agricultural, and algae biomasses. Generally, both catalysts decreased the yield and increased the quality at the same time, and more acidic catalysts decreased the yield further. Thus, zeolites usually decreased the yield more than metal oxides. Although the quality was increased, the oxygen content and calorific value were both increased, which favored further applications. Wood biomass had a lower ash content and nitrogen content than herbaceous, agricultural, and algae biomasses, simultaneously resulting in better yield and quality. This review helps understand the current status of bio-oil investigations and can help find new research directions in the future.

Efficacy of intraoperative sedation combined with preemptive analgesia for single-level kyphoplasty under local anesthesia: A randomized clinical trial.

BACKGROUND: Kyphoplasty is widely used for Osteoporotic Vertebral Compression Fracture (OVCF) under general or local anesthesia, more attention was paid to its post-operative efficacy. Patients' pain and discomfort control strategies during surgery have not been taken seriously. OBJECTIVE: This study aimed at assessing the efficacy of preoperative preemptive analgesia combined with intraoperative sedation for pain and tension relief in OVCF patients undergoing kyphoplasty under local anesthesia. METHODS: We enrolled 128 patients with single-level OVCF who underwent kyphoplasty in our hospital from July 2013 to July 2016. The patients were randomly allocated into three groups: conventional group (i.e., local anesthesia with 0.5% lidocaine (1); n = 42), preemptive group (i.e, (1) + oral 200 mg Celecoxib on the night before surgery with intravenous 40 mg parecoxib sodium an hour before surgery (2); n = 43), and combined group (i.e., (1) + (2) + continuous intravenous 0.5 µg/kg/h dexmedetomidine intraoperatively; n = 43). Hemodynamic variations (heart rate, blood pressure, pulse oxygen saturation (SpO2)), Pain Visual Analogue Score (VAS), Ramsay score, and adverse events were recorded during perioperative period. RESULTS: Blood pressure and heart rate were more stable with significantly smaller values in the combined group than in the conventional and preemptive groups both intra- and postoperatively. In contrast, SpO2 showed no significant difference among the groups throughout the perioperative period. Intraoperative VAS scores revealed significant differences among the groups with the combined group having the smallest values followed by the preemptive group. Similarly, intraoperative Ramsay scores reflected significantly more favorable effects of sedation in the combined than in conventional group. Both VAS and Ramsay scores showed no significant differences among the groups postoperatively, and no differences in complication incidences were noted among the groups as well. CONCLUSIONS: For kyphoplasty under local anesthesia for single-level OVCF, intraoperative sedation combined with preemptive analgesia worked better in mitigating pain and tension intraoperatively and in preventing hemodynamic changes intra- and post-operatively, as compared to local anesthesia alone or additional preemptive analgesia.

Clinical analysis of 2152 cases of abnormal uterine bleeding treated by NovaSure endometrial ablation.

OBJECTIVE: To evaluate the efficiency, postoperative hysterectomy rate, and influencing factors for therapeutic effect of the NovaSure endometrial ablation procedure in abnormal uterine bleeding (AUB). METHODS: We conducted a retrospective cohort study of 2152 patients from the Department of Gynecology at the Third Xiangya Hospital, CSU from October 2010 to December 2018. RESULTS: From the first year to the eighth year after operation, annual effective rate was above 95.24%, and the differences were not statistically significant. There are statistically significant differences between the effective and ineffective groups with regard to age, intrauterine polyps, total length of the uterus, systemic coagulation disorder, and preoperative hemoglobin. A multivariate logistic regression analysis showed that the risk factors associated with systemic coagulation disorders (P = 0.027) and high total uterine length (P = 0.003) affected NovaSure efficacy in the treatment of AUB. By December 2019, the postoperative hysterectomy rate was 1.86% (40/2152) and the complication rate was 1.67% (36/2152). CONCLUSION: NovaSure is a reliable treatment for AUB and serious medical complications because of its simple operation, low amount of bleeding, quick postoperative recovery, and safe and effective short-term and long-term efficacy. However, it should be carefully selected for patients with a total uterus length exceeding 10 cm.