Neonatal IL-4 Over-Exposure is Accompanied by Macrophage Accumulation in Dura Mater After Instant Anti-inflammatory Cytokine Response in CSF.

Multiple studies have shown that clinical events resulting into neonatal IL-4 over-exposure, such as asthma in early life and food allergy, were associated with brain damage and that the neuroinflammation induced by them might lead to cognitive impairments, anxiety-/depressive-like behaviors. IL-4 is the most major elevated cytokine in periphery when these clinical events occur and peripheral IL-4 level positively correlates with the severity of those events. Our previous studies have verified that neonatal IL-4 over-exposure induced a delayed neuroinflammatory damage in rodents, which might have adverse implications for brain development and cognition. Neuroinflammation in brain parenchyma is often accompanied by changes in CSF cytokines levels. However, whether the cytokines levels in CSF change after neonatal IL-4 over-exposure is unknown. Here, we found a delayed pro-inflammatory cytokines response (higher IL-6, IL-1ß and, TNF levels) in both hippocampus and CSF after an instant anti-inflammatory cytokine response in IL-4 over-exposed rats. Moreover, the pro-inflammatory cytokines response appeared earlier in CSF than in hippocampus. The level of each of the pro-inflammatory cytokines in CSF positively correlated with that in hippocampus at the age of postnatal day 42. More microglia numbers/activation and higher M-CSF level in the hippocampus in IL-4 over-exposed rats were also observed. Furthermore, there were more macrophages with inflammatory activation in dural mater of IL-4 over-exposed rats. In sum, neonatal IL-4 over-exposure in rats induces delayed inflammation in CSF, suggesting CSF examination may serve as a potential method in predicting delayed neuroinflammation in brain following neonatal IL-4 over-exposure.

HM_ADET: a hybrid model for automatic detection of eyelid tumors based on photographic images.

BACKGROUND: The accurate detection of eyelid tumors is essential for effective treatment, but it can be challenging due to small and unevenly distributed lesions surrounded by irrelevant noise. Moreover, early symptoms of eyelid tumors are atypical, and some categories of eyelid tumors exhibit similar color and texture features, making it difficult to distinguish between benign and malignant eyelid tumors, particularly for ophthalmologists with limited clinical experience. METHODS: We propose a hybrid model, HM_ADET, for automatic detection of eyelid tumors, including YOLOv7_CNFG to locate eyelid tumors and vision transformer (ViT) to classify benign and malignant eyelid tumors. First, the ConvNeXt module with an inverted bottleneck layer in the backbone of YOLOv7_CNFG is employed to prevent information loss of small eyelid tumors. Then, the flexible rectified linear unit (FReLU) is applied to capture multi-scale features such as texture, edge, and shape, thereby improving the localization accuracy of eyelid tumors. In addition, considering the geometric center and area difference between the predicted box (PB) and the ground truth box (GT), the GIoU_loss was utilized to handle cases of eyelid tumors with varying shapes and irregular boundaries. Finally, the multi-head attention (MHA) module is applied in ViT to extract discriminative features of eyelid tumors for benign and malignant classification. RESULTS: Experimental results demonstrate that the HM_ADET model achieves excellent performance in the detection of eyelid tumors. In specific, YOLOv7_CNFG outperforms YOLOv7, with AP increasing from 0.763 to 0.893 on the internal test set and from 0.647 to 0.765 on the external test set. ViT achieves AUCs of 0.945 (95% CI 0.894-0.981) and 0.915 (95% CI 0.860-0.955) for the classification of benign and malignant tumors on the internal and external test sets, respectively. CONCLUSIONS: Our study provides a promising strategy for the automatic diagnosis of eyelid tumors, which could potentially improve patient outcomes and reduce healthcare costs.

Lactobacillus salivarius Ameliorates AFB1-induced hepatotoxicity via PINK1/Parkin-mediated mitophagy in Geese.

Aflatoxin B1 (AFB1) is commonly found in feed ingredients and foods all over the world, posing a significant threat to food safety and public health in animals and humans. Lactobacillus salivarius (L. salivarius) was recorded to improve the intestinal health and performance of chickens. However, whether L. salivarius can alleviate AFB1-induced hepatotoxicity in geese was unknown. A total of 300 Lande geese were randomly assigned to five groups: control group, AFB1 low-dose group (L), L. salivarius+AFB1 low-dose group (LL), AFB1 high dosage groups (H), L. salivarius+AFB1 high dosage groups (LH), respectively. The results showed that the concentrations of ALT, AST, and GGT significantly increased after exposure to AFB1. Similarly, severe damage of hepatic morphology was observed including the hepatic structure injury and inflammatory cell infiltration. The oxidative stress was evidenced by the elevated concentrations of MDA, and decreased activities of GSH-Px, GSH and SOD. The observation of immunofluorescence, real-time PCR, and western blotting showed that the expression of PINK1 and the value of LC3II/LC3I were increased, but that of p62 significantly decreased after AFB1 exposure. Moreover, the supplementation of L. salivarius effectively improved the geese performance, ameliorated AFB1-induced oxidative stress, inhibited mitochondrial mitophagy and enhanced the liver restoration to normal level. The present study demonstrated that L. salivarius ameliorated AFB1-induced the hepatotoxicity by decreasing the oxidative stress, and regulating the expression of PINK1/Parkin-mediated mitophagy in the mitochondria of the geese liver. Furthermore, this investigation suggested that L. salivarius might serve as a novel and safe additive for preventing AFB1 contamination in poultry feed.

Induction of apoptosis by oridonin in nonfunctioning pituitary adenoma cells.

Nonfunctioning pituitary adenoma (NFPA) is one of the major subtypes of pituitary adenomas (PA) and its primary treatment is surgical resection. However, normal surgery fails to remove lesions completely and there remains in lack of frontline treatment, so the development of new drugs for NFPA is no doubt urgent. Oridonin (ORI) has been reported to have antitumor effects on a variety of tumors, but whether it could exhibit the same effect on NFPA requires to be further investigated. The effects of ORI on pituitary-derived folliculostellate cell line (PDFS) cell viability, colony formation, proliferation ability, migration, and invasion were examined by Cell Counting Kit-8, colony formation assay, 5­Ethynyl­2'­deoxyuridine proliferation assay, wound-healing assay, and Transwell assay. The differentially expressed genes in the control and ORI-treated groups were screened by transcriptome sequencing analysis and analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. Cell cycle analysis was performed to detect changes in cell cycle. Annexin V-fluorescein isothiocyanate/propidium iodide staining was performed to detect apoptosis in ORI-treated cells. Western blot assay was performed to detect Bax, Bcl-2, and cleaved Caspase-3 protein expression. ORI inhibited PDFS cell viability and significantly suppressed cell proliferation, migration, and invasion. GO and KEGG results showed that ORI was associated with signaling pathways such as cell cycle and apoptosis in PDFS cells. In addition, ORI blocked cells in G2/M phase and induced apoptosis in PDFS cells. ORI can trigger cell cycle disruption and apoptosis collaboratively in PDFS cells, making it a promising and effective agent for NFPA therapy.

Multimodal Engineering of Catalytic Interfaces Confers Multi-Site Metal-Organic Framework for Internal Preconcentration and Accelerating Redox Kinetics in Lithium-Sulfur Batteries.

The development of highly efficient catalysts to address the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium-sulfur batteries (LSBs) remains a formidable challenge. In this study, a series of multi-site catalytic metal-organic frameworks (MSC-MOFs) were elaborated through multimodal molecular engineering to regulate both the reactant diffusion and catalysis processes. MSC-MOFs were crafted with nanocages featuring collaborative specific adsorption/catalytic interfaces formed by exposed mixed-valence metal sites and surrounding adsorption sites. This design facilitates internal preconcentration, a coadsorption mechanism, and continuous efficient catalytic conversion toward polysulfides concurrently. Leveraging these attributes, LSBs with an MSC-MOF-Ti catalytic interlayer demonstrated a 62 % improvement in discharge capacity and cycling stability. This resulted in achieving a high areal capacity (11.57 mAh cm-2 ) at a high sulfur loading (9.32 mg cm-2 ) under lean electrolyte conditions, along with a pouch cell exhibiting an ultra-high gravimetric energy density of 350.8 Wh kg-1 . Lastly, this work introduces a universal strategy for the development of a new class of efficient catalytic MOFs, promoting SRR and suppressing the shuttle effect at the molecular level. The findings shed light on the design of advanced porous catalytic materials for application in high-energy LSBs.

Hepatotoxicity evaluation and possible mechanisms of decabrominated diphenyl ethers (BDE-209) in broilers: Oxidative stress, inflammatory, and transcriptomics.

Decabrominated diphenyl ether (BDE-209), a persistent organic pollutant, is linked to a great number of health problems, the most severe of which impact the liver due to its role in the elimination and degradation of exogenous harmful substances. Though the hepatotoxicity of BDE-209 has been observed, its underlying mechanism is yet unknown. The purpose of this study is to thoroughly investigate the hepatotoxicity of BDE-209 and its molecular processes in broilers by subjecting 120 male broilers to varied concentrations of BDE-209 for 42 days. We observed that the bioaccumulation of BDE-209 in the liver in a dose-dependent manner, and that BDE-209 exposure can raise the concentrations of ALT, AST, and GGT, accompanied by hepatocyte fatty degeneration and inflammatory foci. In the hepatic homogenates, oxidative stress was evidenced by elevated levels of MDA and ROS and decreased activies of SOD and CAT. Additionally, pro-inflammatory cytokines including IL-1, IL-1ß, TNF-α, IL-8 levels were increased, whereas anti-inflammatory cytokine IL-4 level was declined. Furthermore, RNA sequencing revealed that genes involved in inflammation were considerably dysregulated, and real-time PCR verified the expressed alterations of numerous genes related to the MAPK and WNT signaling pathways. The protein concentrations of NF-κB, ß-catenin, and WNT5A, and the phosphorylation levels of JNK and ERK were all dramatically enhanced. The current study indicates that BDE-209 exposure can cause hepatotoxicity in broilers via bioaccumulation and oxidative stress, which then activates the MAPK and WNT signaling pathways, subsequently generating inflammation and hepatic injury.

Electrochemical skin conductance and heart rate variability in patients with non-dialysis chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is very common now and associates with high overall and cardiovascular mortality. Numerous studies have reported that Heart rate variability (HRV) could also be used to detect cardiovascular autonomic dysfunction (CAD). We investigated the association of electrochemical skin conductance (ESC) of EZSCAN results with HRV in non-dialysis CKD patients. METHODS: In a cross-sectional study, we enrolled 248 prevalent non-dialysis CKD patients. Patients underwent a 24-h Holter (CB-2302-A, Bio Instrument, China). A time domain analysis of HRV was performed, and the following parameters were obtained: SDNN, SDANN, rMSSD, pNN50. EZSCAN device (Impeto Medical, Paris, France) measures ESC values of each participants. Mean global skin conductance computed as 0.5 * (reflecting (right + left hand)/2 + (right and left foot)/2). Log transforms data into a normal distribution for statistical analysis. RESULTS: There were 142 males and 106 females included in the present study. Patients' age was 56.6±17.08 years. Logarithm(Log) (global ESC) was independently predicted by age (P<0.01), hypertension history, estimated Glomerular filtration rate (eGFR) and log SDNN (P<0.05). While log SDANN, rMSSD and pNN50 were not independent predictors for log (global ESC). CONCLUSION: Increased global ESC significantly associated with elevated HRV, specifically SDNN in non-dialysis CKD patients. This suggested that global ESC may appear to be an important predictor of CAD, and even could be used as a cardiovascular risk factor in non-dialysis CKD patients.

First Report of Root Rot on Paris polyphylla var. yunnanensis caused by Fusarium solani in Yunnan, China.

Paris polyphylla var. yunnanensis is a perennial herb with diverse chemical components having wide-ranging pharmacological effects. The demand for P. polyphylla var. yunnanensis as a raw material increases greatly and currently exceeds 1,000 tons per year (Zhou et al. 2021). In September 2021, root rot was observed on P. polyphylla var. yunnanensis in Mangshi, Yunnan province, China. Average disease incidences in the fields reached 15%, with diseased plants exhibiting yellowing and wilting leaves, as well as browning and rotting roots. Cross sections (5 × 5 mm2) cut from the margin of symptomatic and asymptomatic root tissues were surface-sterilized for 30 s with 75% ethanol, followed by 180 s with 1% sodium hypochlorite. After rinsing thrice with sterile distilled water, the fragments were transferred to potato dextrose agar (PDA) plates and incubated at 28°C in the dark. Ten isolates were obtained, and single spore isolation was performed. These isolates showed similar morphological characters, with colonies ranging in color from white to pale cream and sparse mycelia. Conidia were produced on the top or side of phialides. Microconidia were oval or reniform, 0- or 1-septate, with a diameter of 5.1-10.7 µm × 1.6-3.9 µm (average 7.6 µm × 2.8 µm) (n=30). The macroconidia were straight to slightly curved or sickle-shaped, 3- to 5-septate, with a diameter of 15.1-27.9 µm × 2.8-4.0 µm (average 21.0 µm × 3.6 µm). Chlamydospores were smooth, nearly round, and 3.3-6.6 (average 4.9) µm in diameter. Genomic DNA were extracted from mycelia of the two isolates. The nuclear ribosomal internal transcribed spacer (ITS), translation elongation factor 1 alpha (EF1α), and the second largest subunit of nuclear DNA-directed RNA polymerase II (RPB2) were amplified with the primer pairs of ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), and fRPB2-5F/fRPB2-7cR (Liu et al. 1999), respectively. These two isolates exhibited the same nucleotide sequences (ITS, OP646781; EF1α, OP661172; RPB2, OP661173), with BLASTn analyses showing 100%, 99.66%, and 99.65% identity, respectively, with Fusarium solani (syn. Neocosmospora solani) (Crespo et al. 2019) strain NRRL 43474 (ITS, EF453097; EF1α, EF452945; RPB2, EF469984). A phylogenetic tree was constructed using MEGAX based on the nucleotide sequences of ITS, EF1α, and RPB2, using the maximum likelihood method. The isolate was classified into the F. solani clade. According to the morphology and sequence analyses, the isolate was identified as F. solani (Chehri et al. 2015), and named PpFs1. To test the pathogenicity of the isolate PpFs1, the roots of four years old P. polyphylla var. yunnanensis plants were dipped in 107 spore/mL suspension filtered from potato dextrose broth (PDB) for 30 min, while control roots were dipped in sterile water. After inoculation, all plants were transplanted in pots filled with sterile soil and kept at 25°C with a 12/12-h light/darkness photoperiod. Six plants were used for each treatment, and repeated thrice. Two months after inoculation, the infected plants showed wilted leaves and rotted roots, while controls remained asymptomatic. PpFs1, identified by morphology and ITS, was re-isolated from infected plants, and was found to comply with Koch's postulates. To the best of our knowledge, F. oxysporum and F. concentricum causes Paris polyphylla var. Chinensis stem rot in China. But this is the first report of root rot on P. polyphylla var. yunnanensis being caused by F. solani in Yunnan, China.

UAV-Assisted Cluster-Based Task Allocation for Mobile Crowdsensing in a Space-Air-Ground-Sea Integrated Network.

Mobile crowdsensing (MCS), which is a grassroots sensing paradigm that utilizes the idea of crowdsourcing, has attracted the attention of academics. More and more researchers have devoted themselves to adopting MCS in space-air-ground-sea integrated networks (SAGSINs). Given the dynamics of the environmental conditions in SAGSINs and the uncertainty of the sensing capabilities of mobile people, the quality and coverage of the sensed data change periodically. To address this issue, we propose a novel UAV-assisted cluster-based task allocation (UCTA) algorithm for MCS in SAGSINs in a two-stage process. We first introduce the edge nodes and establish a three-layer hierarchical system with UAV-assistance, called "Platform-Edge Cluster-Participants". Moreover, an edge-aided attribute-based cluster algorithm is designed, aiming at organizing tasks into clusters, which significantly diminishes both the communication overhead and computational complexity while enhancing the efficiency of task allocation. Subsequently, a greedy selection algorithm is proposed to select the final combination that performs the sensing task in each cluster. Extensive simulations are conducted comparing the developed algorithm with the other three benchmark algorithms, and the experimental results unequivocally endorse the superiority of our proposed UCTA algorithm.

Aspirin does not affect hematoma growth in severe spontaneous intracranial hematoma.

Hematoma growth (HG) affects the prognosis of patients with spontaneous intracranial hematoma (ICH), but there is still a lack of evidence about the effects of aspirin (acetylsalicylic acid, ASA) on HG in patients with severe ICH. This study retrospectively analyzed patients with severe ICH who met the inclusion and exclusion criteria in Beijing Tiantan Hospital, Capital Medical University, between January 1, 2015, and July 31, 2019. Severe ICH patients were divided into ASA group and nASA groups according to ASA usage, and the incidence of HG between the groups was compared. Univariate analysis was performed by the Mann-Whitney U test, chi-square test, or Fisher exact test. Multivariate logistic regression analysis was used to analyze the impact of ASA on HG and to screen for risk factors of HG. In total, 221 patients with severe ICH were consecutively enrolled in this study. There were 72 (32.6%) patients in the ASA group and 149 patients in the nASA group. Although the incidence of HG in the nASA group was higher than that in the ASA group (34.9% VS 22.2%, p = 0.056), ASA did not significantly affect the occurrence of HG (p = 0.285) after adjusting for initial hematoma volume, high blood pressure at admission, coronary heart disease, and GCS at admission. In addition, we found that high blood pressure at admission was a risk factor for HG. Prior ASA does not increase the incidence of HG in severe ICH patients, and high blood pressure at admission is a risk factor for HG.

A nomogram to predict the risk of postoperative intracranial rebleeding in patients with spontaneous intracranial hematoma.

The 30-day mortality rate of spontaneous cerebral hemorrhage (ICH) is approximately 30-50%. Surgery may improve the prognosis of patients with severe ICH. However, ICH survivors after surgery still face the risks of postoperative intracranial rebleeding (PIB), and clinical tools that accurately predict the risk of PIB occurrence are not available. Therefore, a retrospective study was performed. The population was divided into two groups according to the occurrence of PIB. Univariate and multivariate logistic regression analyses were performed to screen risk factors for PIB. Next, an early PIB risk nomogram prediction model was constructed. In addition, the impact of PIB on the prognosis of ICH was evaluated. In total, 150 ICH patients were continuously enrolled in this study; 21 patients suffered from PIB, and the overall incidence of PIB was 14.0% (21/150). Coronary heart disease history, a lower GCS score, and subarachnoid hemorrhage absence were screened as risk factors for early PIB. The early PIB risk nomogram showed good calibration and discrimination with a concordance index of 0.807 (95% confidence interval (CI), 0.715-0.899), which was confirmed to be 0.788 through bootstrapping validation. In addition, a significant difference in discharged GOS scores (P = 0.043) was observed between the PIB group and the n-PIB group. These results showed that a history of coronary heart disease, a lower GCS score, and absence of subarachnoid hemorrhage were risk factors for early PIB. In addition, the early PIB risk nomogram prediction model exhibits good discrimination and calibration. The occurrence of PIB could reduce the prognosis of ICH patients.

Toxicokinetics and edible tissues-specific bioaccumulation of decabrominated diphenyl ethers (BDE-209) after exposure to the broilers.

Decabromodiphenyl ether (BDE-209), the primary constituent of a widely used flame retardant formulation, is often present in high levels in avian derived products and could be transferred to humans through consumption. The purpose of this study was to investigate the toxicokinetics and bioaccumulation patterns of BDE-209 in different tissues of broilers, which would benefit the evaluation of chicken product safety. Male broilers received a single oral administration of BDE-209 at 25 mg/kg.BW and then BDE-209 concentrations in the plasma, liver, leg muscle, breast muscle, and other tissues were measured using gas chromatography-electron capture detection (GC-ECD). The changes of BDE-209 concentrations in the plasma were fitted to a non-compartmental model for kinetic analysis. Peak values were observed at 24 h (t1/2 =168.28 h), and trace levels remained for four weeks. Additionally, Cmax in the liver was much higher than that in leg and breast muscles, and Tmax from the liver and muscle were 12 and 24 h, respectively. Residual BDE-209 was detected in all broiler tissues after 2 weeks, and concentrations were ranked as follows: fat > liver > thymus gland > heart > testis > thigh muscle > skin > lung > kidney > breast muscles > spleen (wet weight (ww)). Our results suggested that BDE-209 was widely distributed in different tissues after intestinal absorption, and preferentially accumulated in adipose and liver tissues. Observations of bioaccumulation and slow elimination in the liver and muscles provide critical insight into the toxicity of BDE-209 and risk assessment of edible tissues from broilers.

Preoperative antiplatelet therapy may be a risk factor for postoperative ischemic complications in intracranial hemorrhage patients.

BACKGROUND AND PURPOSE: Spontaneous intracranial hemorrhage (ICH) patients are still at risk of postoperative ischemic complications (PICs) after surgery. In addition, the proportion of patients receiving antiplatelet therapy (APT) in ICH patients increased significantly with age. This study aims to evaluate the impact of preoperative antiplatelet therapy on PICs in ICH patients. METHODS: This is a cohort study that retrospectively analyzed the data of ICH patients who underwent surgical treatment. PICs rate was compared between patients with preoperative ATP and those without preoperative ATP. Univariate and multivariate analyses were conducted to evaluate the impact of preoperative APT on PICs. In addition, Kaplan-Meier method was used for survival analysis and the impact of PICs on patients' postoperative outcomes was evaluated. RESULTS: A total of 216 patients were included in this study. There were 47 patients (21.76%) with preoperative APT; 169 patients (78.24%) without preoperative APT. The incidence of PICs in the APT group was significantly higher when compared with that in the nAPT group (36.17% vs. 20.71%, p = 0.028＜0.05). Furthermore, significant differences were both observed in multivariate analysis (p = 0.035＜0.05) and survival analysis (log rank χ2 = 5.415, p = 0.020＜0.05). However, there was no significant difference between the outcomes of patients suffering from PICs and that of patients not suffering from PICs (p = 0.377 > 0.05). CONCLUSIONS: In conclusion, preoperative APT may be a risk factor for PICs in ICH patients undergoing surgical treatment significantly.

Phloroglucinol Derivative Carbomer Hydrogel Accelerates MRSA-Infected Wounds' Healing.

Globally, wound infection is considered to be one of the major healthcare problems, with bacterial infections being the most critical threat, leading to poor and delayed wound healing, and even death. As a superbug, methicillin-resistant Staphylococcus aureus (MRSA) causes a profound hazard to public health safety, prompting us to search for alternative treatment approaches. Herein, the MTT test and Hoechst/propidium iodide (PI) staining demonstrated that PD was slightly less toxic to human fibroblasts including Human keratinocytes (HaCaT) cell line than Silver sulfadiazine (SSD), and Vancomycin (Van). In the MRSA-infected wound model, PD hydrogel (1%, 2.5%) was applied with for 14 days. The wound healing of PD hydrogel groups was superior to the SSD, Van, and control groups. Remarkably, the experimental results showed that PD reduced the number of skin bacteria, reduced inflammation, and upregulated the expression of PCNA (keratinocyte proliferation marker) and CD31 (angiogenesis manufacturer) at the wound site by histology (including hematoxylin-eosin (HE) staining, Masson staining) and immunohistochemistry. Additionally, no toxicity, hemocompatibility or histopathological changes to organs were observed. Altogether, these results suggested the potential of PD hydrogel as a safe, effective, and low toxicity hydrogel for the future clinical treatment of MRSA-infected wounds.

Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

BACKGROUND: Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer. METHODS: We performed a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer during the 2010-2013 period at Commission on Cancer-accredited hospitals in the United States. The study used inverse probability of treatment propensity-score weighting. We also conducted an interrupted time-series analysis involving women who underwent radical hysterectomy for cervical cancer during the 2000-2010 period, using the Surveillance, Epidemiology, and End Results program database. RESULTS: In the primary analysis, 1225 of 2461 women (49.8%) underwent minimally invasive surgery. Women treated with minimally invasive surgery were more often white, privately insured, and from ZIP Codes with higher socioeconomic status, had smaller, lower-grade tumors, and were more likely to have received a diagnosis later in the study period than women who underwent open surgery. Over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery (hazard ratio, 1.65; 95% confidence interval [CI], 1.22 to 2.22; P=0.002 by the log-rank test). Before the adoption of minimally invasive radical hysterectomy (i.e., in the 2000-2006 period), the 4-year relative survival rate among women who underwent radical hysterectomy for cervical cancer remained stable (annual percentage change, 0.3%; 95% CI, -0.1 to 0.6). The adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI, 0.3 to 1.4) per year after 2006 (P=0.01 for change of trend). CONCLUSIONS: In an epidemiologic study, minimally invasive radical hysterectomy was associated with shorter overall survival than open surgery among women with stage IA2 or IB1 cervical carcinoma. (Funded by the National Cancer Institute and others.).

Multidimensional predicting model of intracranial aneurysm stability with backpropagation neural network: a preliminary study.

OBJECTIVES: The stability of intracranial aneurysms (IAs) may involve in multidimensional factors. Backpropagation (BP) neural network could be adopted to support clinical work. This preliminary study aimed to delve into the feasibility of BP neural network in assessing the risk of IA rupture/growth and to prove the advantage of multidimensional model over single/double-dimensional model. METHODS: Thirty-six IA patients were recruited from a prospective registration study (ChiCTR1900024547). All patients were followed up until aneurysm ruptured/grew or 36 months after being diagnosed with the IAs. The multidimensional data regarding clinical, morphological, and hemodynamic characteristics were acquired. Hemodynamic analyses were conducted with patient-specific models. Based on these characteristics, seven models were built with BP neural network (the ratio of training set to validation set as 8:1). The area under curves (AUC) was calculated for subsequent comparison. RESULTS: Forty-five characteristics were determined from 36 patients with 37 IAs. In the models based on the single dimension of IA characteristics, only morphological characteristics exhibited high performance in assessing 3-year IA stability (AUC = 0.703, P = 0.035). Among the models integrating two dimensions of IA characteristics, clinical-morphological (AUC = 0.731, P = 0.016), clinical-hemodynamic (AUC = 0.702, P = 0.036), and morphological-hemodynamic (AUC = 0.785, P = 0.003) models were capable of assessing the risk of 3-year IA rupture/growth. Moreover, the models including all three dimensions exhibited the maximum predicting significance (AUC = 0.811, P = 0.001). CONCLUSION: The present preliminary study reported that BP neural network might support assessing the 3-year stability of IAs. Models based on multidimensional characteristics could improve the assessment accuracy for IA rupture/growth.

Emergency surgery is an effective way to improve the outcome of severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet therapy.

The necessity of emergency surgery for severe spontaneous intracerebral hemorrhage (SSICH) patients on long-term oral antiplatelet therapy (LOAPT) remains unclear. The aim of this study was to investigate the effect and safety of emergency surgery for SSICH patients on LOAPT (SSICH-LOAPT patients). In this study, a retrospective review of patients admitted to our institution for SSICH from January 2012 to December 2018 was conducted. The collected data included demographic, clinical, and surgical information. The outcome was recorded at 3 months after primary hemorrhage. The outcome of SSICH-LOAPT patients receiving emergency surgery and conservative treatment were compared. The risk of postoperative intracranial bleeding (PIB) in operated SSICH-LOAPT patients was further investigated. A total of 522 SSICH patients were retrospectively reviewed, including 181 SSICH-LOAPT patients and 269 operated patients. The total mortality and in-hospital mortality were 40.6% and 19.3%, respectively. As compared with SSICH-LOAPT patients receiving conservative treatment, the operated SSICH-LOAPT patients showed a lower total (p = 0.043) and in-hospital mortality (p = 0.024). When compared with operated patients not on LOAPT, the operated patients on LOAPT exhibited a higher rate of PIB (OR, 2.34; 95% CI 1.14-4.79; p = 0.018). As demonstrated by the multivariate logistic analysis, dual antiplatelet therapy were independent risk factors associated with PIB in operated SSICH-LOAPT patients (OR, 3.42; CI, 1.01-11.51; p = 0.047). Despite of increasing risk of PIB, emergency surgery could improve the outcome of SSICH-LOAPT patients as it could be effective in reducing mortality. Dual antiplatelet therapy was the independent risk factor related to the PIB in operated SSICH-LOAPT patients.

A nomogram to predict the risk of early postoperative ischemic events in patients with spontaneous intracranial hematoma.

Spontaneous intracranial hematoma (ICH) is the second leading cause of stroke and has a high risk of postoperative ischemic events (PIEs). But, the evidence on PIEs in ICH patients still lacks. Therefore, a retrospective study was carried out to screen the risk factors for PIEs and construct a visual predictive model. This was a retrospective study whose population were divided into two groups based on the occurrence of PIEs. Univariate logistic regression analysis was used to determine factors associated with PIEs. Multifactorial logistic regression analysis was used to screen risk factors and construct the early PIEs risk nomogram. In addition, impact of PIEs on patient prognosis and surgery related costs was assessed. Out of 122 ICH patients, 24 (19.7%) were diagnosed with PIEs. Coronary heart disease history, ischemic stroke history, regular shaped hematoma and platelet number were identified as risk factors for early PIEs. Early PIEs risk nomogram showed good calibration and discrimination of the data with concordance index of 0.846 (95% confidence interval, 0.747-0.945) which was confirmed to be 0.827 through bootstrapping validation. In addition, there was statistical difference in discharged Glasgow Coma Scale score (P = 0.046) and surgery related costs (p = 0.031) between PIEs group and nPIEs group. These results showed the early PIEs risk nomogram was accurate for prediction risks of PIEs and the occurrence of PIEs affects prognosis of patients, and increases surgery related costs.

BDE-47 induces nephrotoxicity through ROS-dependent pathways of mitochondrial dynamics in PK15 cells.

2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced nephrotoxicity is closely associated with oxidative stresses and mitochondrial abnormalities. Mitochondrial fusion and fission dynamics are crucial for maintaining mitochondrial and cellular physiological homeostasis. However, the detailed mechanisms through which BDE-47 disrupts this dynamic and contributes to renal injuries are still not fully understood. The porcine kidney-15 (PK15) cell line, a well-defined in vitro animal renal toxicological model, was exposed to BDE-47 with concentrations of 12.5, 25, 50, and 100 µM, respectively. Cell viability, the levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP), the mitochondrial membrane potential (MMP), and the expression levels of key mitochondrial fusion and fission proteins were assessed. BDE-47 reduced cell viability and disrupted mitochondrial dynamics by inhibiting mitochondrial fusion and fission simultaneously, leading to MMP decreases, ROS overgeneration, ATP depletion, and cellular disintegration in a dose-dependent manner. Additionally, the mitochondrial division inhibitor (Mdivi-1) with the concentration of 20 µM observed to restore the downregulation of mitochondrial fusion and fission proteins, alleviate damages in mitochondrial morphology and functionality, correct ROS overproduction, and enable cell survival. The antioxidant N-acety-L-cysteine (NAC) with the concentration of 1 mM also simultaneously reversed the imbalance of mitochondrial dynamics, decreased ROS production, and restored mitochondrial morphology in PK15 cells exposed to BDE-47. Our data provide new insights indicating that BDE-47 disrupts mitochondrial fusion/fission dynamics to induce mitochondrial abnormalities, triggering oxidative stresses and thus contributing to PK15 cell dysfunction. ROS-dependent pathways in mitochondrial dynamics may provide a new avenue for developing effective strategies to protect cells against BDE-47-induced nephrotoxicity.