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LMO2 is a well-known leukemic proto-oncogene, its ectopic expression in T-lineage specifically initiates malignant transformation of immature T cells and ultimately causes the onset of acute T-lymphocytic leukemia (T-ALL) in both mouse models and human patients. In this study, we systematically explored the LMO2 performance on the profiles of transcriptome, DNA-binding and protein interactions during T-lineage development in the pre-leukemic stage. Our data indicated that large-scale transcriptional dysregulation caused by LMO2 primarily occurred in DN3 thymocytes, characterized by enriched upregulation of the target genes of typical LMO2 complex, RUNX, ETS and STATs, and ectopic LMO2 primarily targeted to RUNX motifs along with intensive interaction with RUNX1 and H3K4 methyltransferase component ASH2L in this stage. However, binding of LMO2 on specific motifs was largely reduced in the following DP and SP stages, along with gradually disappeared LMO2-RUNX1 and LMO2-ASH2L interactions and less alteration of certain transcriptional factor profiles. Moreover, LMO2 showed relatively less influence on cellular behavior of DN3 thymocyte whereas displayed more prominent effects in DP and SP stages, including promoting Notch signaling and cell cycles. These findings provide a high-resolution landscape of the pathogenic role of LMO2 during T-lineage development in molecular level, and may benefit further clinical investigations for LMO2-associated T-lineage malignancies.

To clarify the technical pearls of cavernous sinus molding technique with hemostatic agent injection during endoscopic endonasal pituitary surgery.All patients pretreated with cavernous sinus hemostatic agent injection molding technique for hemostasis in endoscopic endonasal surgery for pituitary adenoma resection between November 2017 and June 2021 were included. A small incision was made in the cavernous sinus wall before intracavernous manipulation. The hemostatic agent was injected with gentle pressure. It spread along the venous channels and established partial molding of the cavernous sinus. Intraoperative bleeding, surgical field score, and complications were evaluated.Thirty-eight patients with pituitary adenoma requiring cavernous sinus manipulation were pretreated with this technique. Technically, the tailored thin blunt metal tube with its 1 cm head end bended up 45° were the best instrument to accomplish injection. Multi-spot injections were preferred to control different compartments of the cavernous sinus, which both had a better effect in bleeding control and helped to reduce the influence of trigemino-cardiac reflex. Postoperative complications, including temporal lobe edema, hemorrhage, and exophthalmos were not observed.Pretreating cavernous sinus with hemostatic agent injection molding technique during endoscopic endonasal pituitary surgery is a practical, effective and safe method for intracavernous bleeding control.

Inositol 1,4,5-Triphosphate Receptor Family (ITPRs) are necessary intracellular Ca2+-release channel encoders and participate in mammalian cell physiological and pathological processes. Previous studies have suggested that ITPRs participate in tumorigenesis of multiple cancers. Nevertheless, the diverse expression profiles and prognostic significance of three ITPRs in pancreatic cancer have yet to be uncovered. In this work, we examined the expression levels and survival dates of ITPRs in patients with pancreatic cancer. As a result, we identified that ITPR1 and ITPR3 expression levels are significantly elevated in cancerous specimens. Survival data revealed that over-expression of ITPR2 and ITPR3 resulted in unfavourable overall survival and pathological stage. The multivariate Cox logistic regression analysis showed that ITPR3 could be an independent risk factor for PAAD patient survival. Moreover, to investigate how ITPRs work, co-expressed genes, alterations, protein-protein interaction, immune infiltration, methylation, and functional enrichment of ITPRs were also analyzed. Then, we evaluated these findings in clinical samples. Moreover, the gain and loss of function of ITPR3 were also conducted. The electron microscope assay was employed to explore the role of ITPR3 in pancreatic cancer cell lines' endoplasmic reticulum stress. In summary, our findings demonstrated that ITPR3 has the potential to be drug targets and biomarkers for human pancreatic cancer.

Motor disorder of upper limbs has seriously affected the daily life of the patients with hemiplegia after stroke. We developed a wearable supernumerary robotic limb (SRL) system using a hybrid control approach based on motor imagery (MI) and object detection for upper-limb motion assistance. SRL system included an SRL hardware subsystem and a hybrid control software subsystem. The system obtained the patient's motion intention through MI electroencephalogram (EEG) recognition method based on graph convolutional network (GCN) and gated recurrent unit network (GRU) to control the left and right movements of SRL, and the object detection technology was used together for a quick grasp of target objects to compensate for the disadvantages when using MI EEG alone like fewer control instructions and lower control efficiency. Offline training experiment was designed to obtain subjects' MI recognition models and evaluate the feasibility of the MI EEG recognition method; online control experiment was designed to verify the effectiveness of our wearable SRL system. The results showed that the proposed MI EEG recognition method (GCN+GRU) could effectively improve the MI classification accuracy (90.04% ± 2.36 %) compared with traditional methods; all subjects were able to complete the target object grasping tasks within 23 seconds by controlling the SRL, and the highest average grasping success rate achieved 90.67% in bag grasping task. The SRL system can effectively assist people with upper-limb motor disorder to perform upper-limb tasks in daily life by natural human-robot interaction, and improve their ability of self-help and enhance their confidence of life.

Cholangiocarcinoma is an extremely malignant cancer with poor prognosis. Finding efficient diagnosis and treatment is the indispensable way to improve the prognosis of CCA patients. Therefore, exploring molecular abnormalities in CCA development is urgently needed. DLEU1 is a potential tumor-related lncRNA and abnormally expressed in multiple cancers. In this study, TCGA data analysis showed upregulation of DLEU1 expression in CCA. Furthermore, we confirmed that DLEU1 expression was increased in CCA tissues and cells compared with corresponding controls. Upregulated DLEU1 was related to poor clinicopathological characteristics. Functionally, silencing DLEU1 inhibited CCA proliferation, invasion, stemness maintenance and chemo-resistance, whereas amplifying DLEU1 promoted malignant biological behavior of CCA cells. Mechanistically, DLEU1 expression was transcriptionally facilitated by transcription factor YY1. Moreover, DLEU1 promoted oncogene YAP1 expression by functioning as a sponge to competitively bind to miR-149-5p. YAP1 promoted CCA proliferation, invasion and stemness maintenance, whereas miR-149-5p inhibited malignant biological behavior of CCA. Rescue experiments confirmed that the cancer-promoting effect of DLEU1 was saved by interfering miR-149-5p or YAP1. Furthermore, YAP1 promoted tumor stemness maintenance partly by acting as a transcriptional coactivator to promote TEAD2-induced SOX2 expression. These findings indicated that YY1-induced DLEU1 played a crucial role in CCA progression via miR-149-5p/YAP1/TEAD2/SOX2 axis.

OBJECTIVES The aim of this study is to systematically evaluate the diagnostic ability of the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) in hepatocellular carcinoma (HCC). METHODS We searched relevant studies from PubMed, Medline, and Embase database. After literature search, duplicate removal, and data extraction, we calculated and analyzed the pooled sensitivity, pooled specificity, pooled odds ratios of diagnostic, pooled likelihood ratio (LR) of positive and negative, and area under the curve (AUC), accuracy, and F1 score to evaluate the diagnostic value of CEUS LI-RADS for HCC. RESULTS Thirteen studies and 6491 patients were included in this analysis. The pooled sensitivity and pooled specificity were 0.72 (95% confidence interval [CI], 0.70-0.73) and 0.92 (95% CI, 0.91-0.93), respectively. The positive LR was 8.02 (95% CI, 4.93-13.06) and the negative LR was 0.31 (95% CI, 0.27-0.37). The pooled diagnostic odds ratio was 27.91 (95% CI, 15.39-50.63). The overall AUC was 0.8406 and the accuracy was 0.77. CONCLUSIONS CEUS LI-RADS is an effective and promising method to diagnose HCC.

Background Much is known about individual sensory deficits among older adults, but there is a dearth of information about the prevalence of multiple concurrent sensory deficits in this population. Methods We evaluated the prevalence of individual and multiple sensory impairments at the most recent clinic visit among participants aged 24 years and older in the Baltimore Longitudinal Study of Aging (BLSA) (hearing, vision, olfaction, proprioception, and vestibular function) and Atherosclerosis Risk in Communities Study (ARIC) (hearing, vision, olfaction). We compared observed prevalence of multiple sensory impairments with expected prevalence based on compounded probabilities of multiple impairments using Fisher Exact Tests. Also, we evaluated the comparability of different measures used between these two studies. Results In both studies, the prevalence of each individual sensory impairment was common (>10%), and higher with older age, and the most common pattern of co-occurring sensory impairments was hearing and visual impairments (17.4% [BLSA]; 50.2% [ARIC]). In BLSA, the pattern that differed the most between observed and expected prevalence was combined hearing, vision, and olfactory impairments (observed 5.2% vs 1.4% expected, p = .01). In ARIC, this difference was much smaller (observed 8.1% vs 7.2% expected, p = .49). Conclusions Although concurrent hearing and vision impairments were the most common co-occurring deficits, combined hearing, vision, and olfactory impairments are most likely to co-occur above chance, especially at older ages.

Objective: The purpose of this work is to study whether the active state and species of biological tissues can influence changes in their dielectric properties. Methods: In this paper, the dielectric properties of liver, kidney and spleen tissues from human active, human inactive and animal tissues are measured in the frequency range of 10 Hz to 100 MHz. The four- and two-electrode methods are used to measure dielectric properties at different frequencies. Statistical analysis and the pattern recognition method are used to compare the dielectric properties of human active tissues, human inactive tissues, animal tissues and data provided by the IFAC database. Results: The results show that the dielectric properties of human active tissues are significantly different from those of human inactive tissues and animal tissues, resulting in a great difference between the dielectric properties provided by the IFAC database and those of human active tissues. The dielectric properties of human active tissues can be identified by the pattern recognition method based on principal component analysis, which further proves that the dielectric properties of human active tissues cannot be replaced. Conclusion: The dielectric properties of biological tissues are closely related to the activity and species of tissues. The dielectric properties of human active tissues cannot be replaced by those of human cadaver tissues or animal tissues. Significance: The significance of this study is suggesting that the IFAC database should be updated with the dielectric properties of human active tissues to provide accurate data for bioelectromagnetics research.

Background Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes. Objective To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs. Design Prospective cohort. (ClinicalTrials.gov: NCT02411396). Setting 4 U.S. sites, with recruitment between April 2015 and December 2016. Participants Adults with SCD living within 60 miles of a study site. Measurements Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment. Results Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant's visit would end in admission to the hospital was smaller by a factor of 4 (0.25 [CI, 0.18 to 0.33]) with treatment in an IC versus an ED. Limitation The study was restricted to participants with uncomplicated VOCs. Conclusion In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED. Primary funding source Patient-Centered Outcomes Research Institute.

The toxicity of organophosphate esters (OPEs) on embryonic development is well noted in animal experiments, but epidemiological studies are still lacking. This study evaluated the prenatal exposure of OPEs and its trimester-specific and gender-specific effects on fetal growth. The correlations between OPE exposure and fetal growth were investigated by linear mixed-effect models and multivariable linear regression analyses. Prenatal exposure to tributyl phosphate (TBP) was negatively associated with a

PurposeNeoadjuvant chemoradiotherapy (nCRT) is a standard treatment option for patients with stage III oesophageal cancer. Approximately 30% of oesophageal cancer patients will have a pathological complete response (pCR) after nCRT. However, available clinical methods cannot accurately predict pCR for patients. We aimed to find more indicators that could be used to predict the pathological response to nCRT.MethodA total of 84 patients with stage III oesophageal squamous cell cancer were enrolled in this study. Ten patients failed to have surgery as a result of progressive disease (PD). Among the patients who underwent surgery, 32 patients had a pathologic complete response (pCR), whereas 42 patients showed no or partial response (npCR) after nCRT. Routine blood test results and lymphocyte subset assessments before and after nCRT were retrospectively analysed. Univariate and multivariate analyses were used to identify independent predictors of the clinical curative effect of nCRT. Eventually, nomograms were established for predicting the PD and pCR rates.ResultsThe numbers of lymphocytes, B lymphocytes, T lymphocytes, Th lymphocytes, Ts lymphocytes, and NK cells and the percentages of B lymphocytes and NK cells were decreased significantly after nCRT (P < 0.0001), whereas the percentages of T lymphocytes and Ts lymphocytes increased (P < 0.0001). Univariate analysis showed that age, the length of the lesion, the level of haemoglobin before nCRT, and the amount of change in haemoglobin were related to PD, and the percentage of NK cells after nCRT was related to pCR. Multivariate logistic analysis demonstrated that the length of the lesion, the neutrophil-to-lymphocyte ratio (NLR) before nCRT, and the amount of change in haemoglobin were independent predictors of PD, whereas the percentage of NK cells after nCRT was an independent predictor of pCR.ConclusionLymphocyte subsets changed dramatically during nCRT, and these changes together with baseline and posttreatment lymphocyte subsets have predictive value in determining the response to nCRT for oesophageal cancer.

Bullous pemphigoid (BP) is a common autoimmune subepidermal bullous disease.The diagnosis of BP relies on clinical manifestation,histopathology,direct and indirect immunofluorescence,and serological assay.In the past two decades,topical corticosteroids and systemic and/or topical corticosteroids were the major therapeutic options for localized/mild/moderate and extensive/severe BP,respectively.In 2021,several experts from the French Study Group on Autoimmune Bullous Skin Diseases collaboratively issued the updated guidelines for the therapeutic management of BP based on evidence-based medicine.The guidelines fully detailed the updated therapeutic options for extensive BP,BP of limited extent,localized form of BP,corticosteroid-dependent BP,and drug-induced/associated BP.In particular,systemic corticosteroids are no longer the first-line treatment for extensive BP.We interpret the guidelines to assist dermatologists in the comprehensive management of BP and promote the standardization of BP treatment.

Background There is no available viable treatment for Sepsis-Induced Cardiomyopathy (SIC), a common sepsis complication with a higher fatality risk. The septic patients showed an abnormal activation of the renin angiotensin (Ang) aldosterone system (RAAS). However, it is not known how the Ang II and Ang-(1–7) affect SIC. Methods Peripheral plasma was collected from the Healthy Control (HC) and septic patients and Ang II and Ang-(1–7) protein concentrations were measured. The in vitro and in vivo models of SIC were developed using Lipopolysaccharide (LPS) to preliminarily explore the relationship between the SIC state, Ang II, and Ang-(1–7) levels, along with the protective function of exogenous Ang-(1–7) on SIC. Results Peripheral plasma Ang II and the Ang II/Ang-(1–7) levels in SIC-affected patients were elevated compared to the levels in HC and non-SIC patients, however, the HC showed higher Ang-(1–7) levels. Furthermore, peripheral plasma Ang II, Ang II/Ang-(1–7), and Ang-(1–7) levels in SIC patients were significantly correlated with the degree of myocardial injury. Additionally, exogenous Ang-(1–7) can attenuate inflammatory response, reduce oxidative stress, maintain mitochondrial dynamics homeostasis, and alleviate mitochondrial structural and functional damage by inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thus alleviating SIC. Conclusions Plasma Ang-(1–7), Ang II, and Ang II/Ang-(1–7) levels were regarded as significant SIC biomarkers. In SIC, therapeutic targeting of RAAS, for example with Ang-(1–7), may exert protective roles against myocardial damage.

Background Iliac vein compression syndrome (IVCS) diagnosis heavily relies on an imaging test. However, non-invasive and contrast-free imaging test for the diagnosis of IVCS remains a big challenge. To address this issue, this prospective study aimed to assess the image quality and diagnostic performance of a magnetic resonance imaging technique, black-blood venous imaging (BBVI), in detecting IVCS by comparing it with contrast-enhanced computed tomography venography (CTV) and using invasive digital subtraction angiography (DSA) as the reference. Methods We enrolled 105 patients, and all patients underwent BBVI, CTV, and DSA examinations. We compared the consistency of CTV and BBVI image quality and their consistency in diagnosing the rate of iliac vein stenosis in IVCS patients. Using the consensus DSA as a reference, the sensitivity, specificity, positive and negative predictive values, and accuracy of BBVI and CTV and their diagnostic agreement with DSA were calculated. Results BBVI demonstrated high sensitivity, specificity, and accuracy for the diagnosis of IVCS, without contrast agents. BBVI and CTV are quite in diagnosis IVCS. Quite SE (67.8% vs 68.3%), SP (94.8% vs 94.8%), PPV (98.0% vs 98.0%), NPV (46.2% vs 46.9%) and ACC (75.3% vs 75.7%) were obtained by BBVI in comparison with CTV. Conclusion BBVI has comparable diagnostic performance with CTV. It may be a viable alternative to CTV techniques in screening the IVCS without contrast agents and free of ionizing radiation.

Hepatobiliary cancers are a heterogeneous group of malignancies with a dismal prognosis. Despite intensive research efforts focused on these tumors, methods for early diagnosis and effective targeted therapies are still lacking. Exosomes, released by most cells, exist in all kinds of body fluids and play an important role in cell-to-cell communication. They are small membranous vesicles containing biological molecules, such as noncoding RNAs (ncRNA), which are not translated into proteins, but they exert effects on the regulation of gene transcription and translation. There is growing evidence for the essential roles of ncRNAs in exosomes in both physiologic and pathologic conditions of hepatobiliary cancers. They have been identified as sensitive diagnostic biomarkers as well as potential therapeutic targets. The present review discusses recent findings in the cross-talk between hepatobiliary cancers cells and the surrounding cells of the microenvironment and discuss their potential clinical usage.

Background We conducted a cost-effectiveness analysis incorporating recent phase III clinical trial (MONALEESA-7) data to evaluate the cost-effectiveness of ribociclib (RIB) as a first-line treatment for premenopausal women with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from the United States healthcare payer perspective. In addition, because RIB has not been marketed in China, we identified the range of drug costs for which RIB could be considered cost effective from a Chinese healthcare system perspective. Patients and Methods A Markov model was developed to evaluate the cost-effectiveness of adding RIB to endocrine therapy over a lifetime. The clinical outcomes and utility data were obtained from published literature. Costs data were obtained from United States and Chinese official websites, and we determined the potential price for RIB in China based on its price in the United States. The main outcomes of this study were the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs). Results The model projected that mean outcome was better with RIB and endocrine combined (3.83366 QALYs) than with endocrine therapy alone (2.71203 QALYs). In the United States, RIB and endocrine therapy cost an additional $604,960.06, resulting in an ICER of $539,357.95/QALY compared with endocrine monotherapy. Subgroup analyses indicated that, in China, the projected mean outcomes were better for RIB and endocrine therapy (6.37 QALYs) than for endocrine monotherapy (2.71 QALYs). The corresponding incremental costs were $224,731.88943. Thus, the ICER comparing RIB and endocrine therapy with endocrine therapy alone represented a $61,454.96/QALY gain. Conclusion Additional use of RIB is estimated to not be cost effective as a first-line treatment for premenopausal women with HR-positive, HER2-negative ABC in the United States. A value-based price for the cost of RIB is less than $31.74/200 mg for China.

Background Intrahepatic cholangiocarcinoma is an aggressive liver carcinoma with increasing incidence and mortality. A good auxiliary prognostic prediction tool is desperately needed for the development of treatment strategies. The purpose of this study was to explore the prognostic value of the radiomics nomogram based on enhanced CT in intrahepatic cholangiocarcinoma. Methods In this retrospective study, 101 patients with pathological confirmation of intrahepatic cholangiocarcinoma were recruited. A radiomics nomogram was developed by radiomics score and independent clinical risk factors selecting from multivariate Cox regression. All patients were stratified as high risk and low risk by a nomogram. Model performance and clinical usefulness were assessed by calibration curve, ROC curve, and survival curve. Results A total of 101patients (mean age, 58.2 years old; range 36–79 years old) were included in the study. The 1-year, 3-year, and 5-year overall survival rates were 49.5%, 26.6%, and 14.4%, respectively, with a median survival time of 12.2 months in the whole set. The least absolute shrinkage and selection operator (LASSO) method selected 3 features. Multivariate Cox analysis found three independent prognostic factors. The radiomics nomogram showed a significant prognosis value with overall survival. There was a significant difference in the 1-year and 3-year survival rates of stratified high-risk and low-risk patients in the whole set (30.4% vs. 56.4% and 13.0% vs. 30.6%, respectively, p = 0.018). Conclusions This radiomics nomogram has potential application value in the preoperative prognostic prediction of intrahepatic cholangiocarcinoma and may facilitate in clinical decision-making.

The molecular mechanism of bone metastasis in breast cancer is largely unknown. Herein, we aimed to identify the key genes and long non-coding RNAs (lncRNAs) related to the bone metastasis of breast cancer using a bioinformatics approach. We screened differentially expressed genes and lncRNAs between normal breast and breast cancer bone metastasis samples using the GSE66206 dataset from the Gene Expression Omnibus. We also constructed a differentially expressed lncRNA-mRNA interaction network and analyzed the node degrees to identify the driving genes. After finding potential pathogenic modules of breast cancer bone metastasis, we identified breast cancer bone metastasis-related modules and functional enrichment analysis of the genes and lncRNAs in the modules. Based on the above analysis, we constructed a differentially expressed lncRNA-mRNA network related to bone metastasis in breast cancer and identified core driver genes, including BNIP3 and the lncRNA RP11-317-J19.1. The role of core driver genes and lncRNAs in the network implies their biological functions in regulating bone development and remodeling. Thus, targeting the core driver genes and lncRNAs in the network may be a promising therapeutic strategy to manage bone metastasis.

Background The optimal first‐line approach for patients with symptomatic atrial fibrillation (AF) remains unclear. We compared the efficacy and safety of cryoballoon ablation (CBA) and antiarrhythmic drugs (AADs) in the initial management of symptomatic AF. Hypothesis CBA is superior to AAD as initial therapy for symptomatic AF. Methods We searched the EMBASE, PubMed, and Cochrane Library databases for randomized controlled trials (RCTs) that compared CBA with AAD as first‐line treatment for AF from the date of database establishment until March 18, 2021. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure of treatment effect. Results Three RCTs that enrolled 724 patients in total were included in this meta‐analysis. Majority of the patients were relatively young and had paroxysmal AF. CBA was associated with a significant reduction in the recurrence of atrial arrhythmia compared with AAD therapy, with low heterogeneity (RR, 0.59; 95% CI, 0.49–0.71; p

Dendritic cell (DC)-derived small extracellular vesicles (DEVs) are recognized as a highly promising alternative to DC vaccines; however, the clinical testing of DEV-based immunotherapy has shown limited therapeutic efficacy. Herein, we develop a straightforward strategy in which DCs serve as a cell reactor to exocytose high-efficient DEV-mimicking aggregation-induced emission (AIE) nanoparticles (DEV-AIE NPs) at a scaled-up yield for synergistic photodynamic immunotherapy. Exocytosed DEV-AIE NPs inherit not only the immune-modulation proteins from parental DCs, enabling T cell activation, but also the loaded AIE-photosensitizer MBPN-TCyP, inducing superior immunogenic cell death (ICD) by selectively accumulating in the mitochondria of tumor cells. Eventually, DEV-AIE synergistic photodynamic immunotherapy elicits dramatic immune responses and efficient eradication of primary tumors, distant tumors, and tumor metastases. In addition, cancer stem cells (CSCs) in 4T1 and CT26 solid tumors were significantly inhibited by the immune functional DEV-AIE NPs. Our work presents a facile method for the cellular generation of EV-biomimetic NPs and demonstrates that the integration of DEVs and AIE photosensitizers is a powerful direction for the production of clinical anticancer nanovaccines.

Bacterial pathogens and antibiotic resistance genes (ARGs) are extensively disseminated into the environment via hospital wastewater (HWW), as it contains large quantities of feces from resident patients. However, studies on the antibiotic resistome and pathogenic bacteria from the gut of resident patients within the hospital wastewater treatment plant (hWWTP) are limited. Here, we examined and compared the occurrence and abundance of ARGs, mobile genetic elements (MGEs), metals, and bacterial communities from the feces of patients in a typical hWWTP system and determined the pathogenic hosts responsible for transferring ARGs. There were 176 ARGs and 43 MGEs detected in the feces of hospitalized patients, 129 genes were persistent, and 88 genes were enriched after HWW treatment, particularly for the bla

The innovation of immunotherapy was a milestone in the treatment of bladder cancer (BLCA). However, the treatment benefits varied by individual thus promoting the investigation of the biomarker of the patients. Unfortunately, there were not many effective predictive models, which were desired by clinicians, for BLCA that can predict the prognosis and benefit of immunotherapy. We constructed a three genes prognosis prediction model termed RiskScore based on the result of weighted correlation network analysis (WGCNA) from The Cancer Genome Atlas (TCGA) cohort (n = 406). We then validated the prediction accuracy with three validation cohort(GSE13507 (n = 165), GSE48075(n = 73), GSE32894(n = 224)). We compared the differences in gene expression, immune relate function, and immune infiltration between two groups divided by RiskScore. We further discovered the potential drug target and suitable compounds for high-risk groups. Our results suggested that the low-risk group may be more potential for immunotherapy for they have higher B cell infiltration, higher expression of immune checkpoints(PDCD1, CTLA4), and much more active immune-related pathways(B cell and T cell receptor signaling pathway). The RiskScore showed a well predictive accuracy for the prognosis of BLCA. After Spearman analysis, we found the suitable drug target and compounds for the patients in the high-risk group. The model we constructed is able to predict the prognosis of BLCA patients with ease and accuracy. PLK1 and gefitinib may be utilized for further treatment of BLCA patients.

Objective To investigate the efficacy and safety of docetaxel chemotherapy combined with androgen-deprivation therapy for patients with high-volume disease metastatic hormone-sensitive prostate cancer. Methods 153 cases of high-volume disease metastatic hormone-sensitive prostate cancer in Minhang Hospital between January 2018 and December 2019 were analyzed retrospectively, including the number of patients, age, initial PSA level, Gleason score, TNM stage and ECOG score. 90 patients in the endocrine therapy group received continuous ADT, and 63 patients in the combined chemotherapy group received docetaxel plus ADT. The progression-free survival time (time from initiation of prostate cancer treatment to progression to CRPC), PSA response rate, and adverse reactions were compared between the two groups. Results All 153 cases were closely followed up for a period of 12.3–35.3 months, with a median follow-up time of 23.5 months. The median time to reach the lowest point of PSA in the two groups was 6.3 months and 7.9 months (P = 0.018) in the combination chemotherapy group and the ADT group alone, with 27 (42.9%) and 12 (13.3%) cases in the two groups Within 12 months of treatment, PSA decreased to below 0.2 ng/ml (P = 0.02), and progression-free survival was 16.9 months (6.5–28.5 months) and 11.2 months (4.3–22.7 months) in the two groups. (P P P = 0.961). Conclusion Docetaxel chemotherapy combined with endocrine therapy could be one of effective treatments for delaying castration resistance of HVD-mHSPC, which could prolong PFS effectively and obtain a higher PSA response rate, high safety under close monitoring, and controllable adverse reactions.

Background To assess the impact of malignant cystic renal masses (CRM) rupture on oncologic outcomes. Methods The study included 406 cases with partial nephrectomy (PN) and 17 cases with cyst decortication confirmed as malignant CRM by pathology. Recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank test. Cox regression was used to identify risk factors associated with RFS, MFS, CSS, and OS. Logistic regression was performed to explore predictors of rupture. Results Tumor rupture occurred in 32 of 406 cases (7.9%). With median follow-up of 43 months, 4 (12.5%) and 5 (1.3%) cases experienced recurrence in rupture and non-rupture group, respectively (P = 0.003). Estimated RFS, MFS, and CSS were shorter in cyst ruptured (CR) group than non-ruptured (nonCR) cases (P < 0.001; P = 0.001; P < 0.001). Cox regression analysis indicated that CR was an independent prognostic factor for RFS (HR = 7.354; 95% CI = 1.839–29.413; P = 0.005), MFS (HR = 8.069; 95% CI = 1.804–36.095; P = 0.006), and CSS (HR = 9.643; 95% CI = 2.183–42.599; P = 0.003). Multivariable logistic regression showed that Bosniak IV was a protective factor for CR (OR = 0.065; 95% CI = 0.018–0.239; P < 0.001). However, compared to Bosniak III and I-IIF, Bosniak IV CRMs showed higher rate of clear cell renal cell carcinoma (ccRCC) (76.8% vs 36.5% vs 81.4%) (P < 0.001) and lower rate of Fuhrman I staging (11.2% vs 66.7% vs 7.4%) (P < 0.001). Therefore, in ruptured cases, the recurrence rate was higher in CRM with Bosniak IV (50%, 2/4) than Bosniak I-III (4.4%, 2/45) (P = 0.029). Conclusions Intraoperative malignant CRM rupture had negative impacts on oncologic outcomes. Bosniak IV was more aggressive than Bosniak I-III and had a higher risk of recurrence after rupture. However, Bosniak IV had a lower risk of rupture, which could weaken even cover-up of the true effect of tumor rupture on oncologic outcomes.

ObjectiveNowadays, platinum-based therapy has been widely used as the first-line therapy of ovarian cancer. However, the effect of the tumor microenvironment on platinum-based therapy remains unclear. In this study, we aim to investigate the relationship between immune microenvironment subtypes and the prognosis of platinum-based therapy in ovarian cancer.MethodsWe integrated 565 ovarian cancer samples from two datasets and obtained the immune subtypes (ISs) by consistent clustering of 1190 immune-related gene expressions. The proportional hazards regression model was used to assess the relationship between ISs and the prognosis of platinum-based adjuvant therapy including progression-free survival (PFS) and overall survival (OS). The prognostic contribution of ISs was validated in three additional cohorts. Non-parametric tests were used to assess genomic characteristics, the proportion of immune cells, and immune-related signature differences among ISs.ResultsWe identified and validated five ISs associated with different clinical outcomes of the platinum-based adjuvant therapy in ovarian cancer patients. These differences were only found in OS rather than PFS. An immune subtype had the worst OS. Those patients mainly derived from the mesenchymal subtype had the lowest tumor purity with a high leukocyte fraction as well as stromal fraction and had the highest TGF-β response signaling. By contrast, an immune subtype characterized by immunoreactive status with the highest CD8+T cell infiltration and elevated IFN-γ response signaling had the best prognosis. Other subtypes with more diverse immunologic features such as lowest macrophage regulation signaling showed intermediate prognoses. Notably, the contribution of ISs to OS was independent of the clinical response to platinum-based drugs.ConclusionOur analysis revealed the association between different immune characteristics and platinum-based adjuvant therapy, indicating the combination of ISs and chemotherapy could optimize the treatment strategy of OC patients.

Background Anatomical knowledge of the zygomatico-orbital artery and its most relevant clinical applications is essential for ensuring the safety of filler injection into the temporal region. The purpose of this study was to provide the precise position, detailed course, and relationship with surrounding structures of the zygomatico-orbital artery. Methods Fifty-eight patients who underwent head contrast-enhanced three-dimensional computed tomography and 10 fresh frozen cadavers were investigated. Results The zygomatico-orbital artery was identified in 93 percent of the samples in this work. Ninety-four percent of the zygomatico-orbital arteries derived directly from the superficial temporal artery, and the remaining arteries started from the frontal branch of the superficial temporal artery. According to the origin of the zygomatico-orbital artery, it was classified into type I and type II. Type I arteries were then classified into three subtypes. The trunk of the zygomatico-orbital artery was located between the deep temporal fascia and the superficial temporal fascia. Deep branches of the zygomatico-orbital artery pierced the superficial layer of the deep temporal fascia. The zygomatico-orbital artery originated from 11.3 mm in front of the midpoint of the apex of the tragus, and most of its trunks were located less than 20.0 mm above the zygomatic arch. The mean diameter of the zygomatico-orbital artery was 1.2 ± 0.2 mm. There were extensive anastomoses between the zygomatico-orbital artery and various periorbital arteries at the lateral orbital rim. Conclusion The precise anatomical knowledge of the zygomatico-orbital artery described in this study could be helpful for cosmetic physicians for improving the safety of temporal augmentation.

Under the global climate warming, extreme weather events occur more and more frequently. Epidemiological studies have proved that extreme temperature is strongly correlated with respiratory diseases. We evaluated extreme-temperature effect on respiratory emergency room (ER) visits for 5 years in Lanzhou, a northwest temperate climate city of China from January 1st, 2013, to August 31st, 2017. We built a distributed lag non-linear model (DLNM) to evaluate the lag effect up to 30 days. Results showed the relative risk (RR) of respiratory disease always reached the maximum at lag 0 day and decreased to 1.0 at lag 5 days. Extremely low temperature showed the lag effect of 22 days and the maximum RR was 1.415 (95% CI 1.295–1.546) at lag 0 day. Extremely high temperature showed the lag effect of 7 days and the maximum RR was 1.091 (95% CI 1.069–1.114) at lag 0 day. The elders (age > 65 years) were at the greatest risk to extreme temperatures and the response were very acute. Children (age ≤ 15 years) were at the lowest risk but the lag effect lasted the longest lag days than other subgroups. Males showed longer-term lag effect and higher RR than females. Our study indicated that the extremely low temperature has a significantly greater effect on respiratory diseases than extremely high temperature.

Background Vision loss is associated with increased risk of falls and restricted physical activity, yet the relationship between multiple vision measures and objectively measured physical activity, especially activity patterns, in mid-to-late life is not well understood. Method This study included 603 participants aged 50 years and older (mean age = 73.5) in the Baltimore Longitudinal Study of Aging who had the following assessments: presenting and best-corrected visual acuity, contrast sensitivity, visual fields, stereo acuity, and free-living physical activity using a wrist-worn ActiGraph accelerometer for 7 days. Linear regression models were used to examine the association between vision measures and daily activity counts, active minutes, and activity fragmentation (defined as an active-to-sedentary transition probability), adjusting for potential confounders. Mixed-effects models estimated differences in activity by time of day comparing those with and without each visual impairment. Results In the fully adjusted model, worse presenting visual acuity, contrast sensitivity, and visual fields were associated with fewer activity counts, less active time, and more fragmented activity patterns (p < .05 for all). Participants with presenting or best-corrected visual acuity impairment had 19.2 and 29.3 fewer active minutes (p = .05 and p = .03, respectively) per day. Visual field impairment was associated with 268 636 fewer activity counts (p = .02), 46.2 fewer active minutes (p = .02) per day, and 3% greater activity fragmentation (p = .009). Differences in activity levels tended to be greatest from 6 am to 6 pm (p < .05). Conclusions Older adults with visual impairment have restricted and more fragmented patterns of daily activity. Longitudinal studies to quantify the long-term impacts of visual impairments on activity decline are warranted.

Urine is an important source of biomolecular information for metabolomic studies. However, the acquisition of high-quality metabolomic datasets or reliable biomarkers from urine is difficult owing to the large variations in the concentrations of endogenous metabolites in the biofluid, which are caused by diverse factors such as water consumption, drugs, and diseases. Thus, normalization or calibration is essential in urine metabolomics for eliminating such deviations. The urine osmolality (Π), which is a direct measure of the total urinary solute concentration and is not affected by circadian rhythms, diet, gender, and age, is often considered the gold standard for estimation of the urine concentration. In this study, a pre-data acquisition calibration strategy based on osmolality was investigated for its feasibility to overcome sample concentration variability. Before data acquisition, the product of the osmolality×injection volume of all samples was set to be equivalent through the uses of a customized injection volume or dilution. After ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) analysis of the sample, the raw dataset was normalized to the total ion abundance or total useful MS signals (MSTUS) to achieve further calibration. The osmolality of each urine sample was determined with a freezing-point depression osmometer. For the instrumental analysis, a Vanquish UPLC system coupled to a Q-Exactive Plus HRMS device was used for metabolite analysis and accurate mass measurement. Full-scan mass spectra were acquired in the range of m/z 60-900, and the MS/MS experiments were conducted in "Top5" data-dependent mode. A Waters UPLC column (100 mm×2.1 mm, 1.8 μm) was used for chromatography separation. The raw data were imported into Progenesis QI software for peak picking, alignment, deconvolution, and normalization. SIMCA-P software was used for the principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). This strategy was first applied to sequentially diluted urine samples, where three frequently used normalization methods were compared. In the identical injection volume experiment, the points were scattered and showed relevant distribution according to the dilution multiple in the plot of PCA scores. There was little improvement after normalization to either the total ion abundance or MSTUS. In the customized injection volume experiment, the urine samples derived from the same source showed ideal clustering. With total ion abundance and MSTUS normalization, the dataset was further improved in the PCA model fitting and prediction. As a result, there were more peaks with a peak area RSD of

BACKGROUND Dark circles are one of the most perplexing cosmetic problems for modern people. Nowadays, a new porcine collagen filler has been popular in China and many countries and has high safety. AIMS The purpose of this study is to explore and quantify the efficacy of this collagen filler in treating structured dark circles objectively and systematically. METHODS This is a prospective study. Twenty patients were included and took standard facial photographs at preoperative (Tp), immediately postoperative (T0), 1 week (T1), 2 weeks (T2), 4 weeks (T4), 8 weeks (T8), and 12 weeks (T12). The efficacy was quantified by measuring the depression of the tear trough and infraorbital melanin content. Three dermatologists blinded to the treatment were responsible for completing the subjective evaluations. RESULTS The depression volume, depression-affected area, and depression maximum depth of the tear trough decreased significantly immediately postoperation, and then all values increased slowly with time (P

Background: Gradual disengagement from daily physical activity (PA) could signal present or emerging mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Objective: This study examined whether accelerometry-derived patterns of everyday movement differ by cognitive diagnosis in participants of the Baltimore Longitudinal Study of Aging (BLSA). Methods: Activity patterns, overall and by time-of-day, were cross-sectionally compared between participants with adjudicated normal cognition (n = 549) and MCI/AD diagnoses (n = 36; 5 participants [14%] living with AD) using covariate-adjusted regression models. Results: Compared to those with normal cognition, those with MCI/AD had 2.1% higher activity fragmentation (SE = 1.0%, p = 0.036) but similar mean total activity counts/day (p = 0.075) and minutes/day spent active (p = 0.174). Time-of-day analyses show MCI/AD participants had lower activity counts and minutes spent active during waking hours (6:00 am–5:59 pm; p

Vibrio cholerae, the etiological pathogen of cholera, employs its type VI secretion system (T6SS) as an effective weapon to survive in highly competitive communities. Antibacterial and anti-eukaryotic functions of the T6SS depend on its secreted effectors that target multiple cellular processes. However, the mechanisms that account for effector diversity and different effectiveness during interspecies competition remain elusive. Here we report that environmental cations and temperature play a key role in dictating cellular response and effector effectiveness during interspecies competition mediated by the T6SS of V. cholerae. We found that V. cholerae could employ its cell-wall-targeting effector TseH to outcompete the otherwise resistant Escherichia coli and the V. cholerae immunity deletion mutant ∆tsiH when Mg(2+) or Ca(2+) was supplemented. Transcriptome and genetic analyses demonstrate that the metal-sensing PhoPQ two-component system is important for Mg(2+)-dependent sensitivity. Competition analysis in infant mice shows that TseH was active under in vivo conditions. Using a panel of V. cholerae single-effector active mutants, we further show that E. coli also exhibited variable susceptibilities to other T6SS effectors depending on cations and temperatures, respectively. Lastly, V. cholerae effector VasX could sensitize Pseudomonas aeruginosa to its intrinsically resistant antibiotic irgasan in a temperature-dependent manner. Collectively, these findings suggest that abiotic factors, that V. cholerae frequently encounters in natural and host environments, could modulate cellular responses and dictate the competitive fitness conferred by the T6SS effectors in complex multispecies communities.

OBJECTIVES The optimal location to insert a chest tube for postoperative drainage has not been identified. We performed a retrospective equivalence study to identify whether the efficiency is similar regarding anterior or posterior position of chest tube in thoracic cavity after video-assisted thoracoscopic surgery for non-small-cell lung cancer. METHODS A retrospective review of 4263 patients undergoing non-small-cell lung cancer resection from October 2009 to August 2019 in the Western China Lung Cancer Database was conducted. Propensity score matching was performed to balance baseline characteristics between anterior and posterior groups. Chest tube duration, drainage volume, postoperative complications and hospitalization cost were compared. Equivalence margin was defined as (−1, 1) in 95% confidence interval of the mean difference of chest tube duration. RESULTS After propensity score matching, we investigated 2912 patients with anterior or posterior (1456 vs 1456) chest tube location following lung cancer resection. The mean time to chest tube removal was 3.39 days in the anterior group and 3.38 days in the posterior group (P = 0.52), while the mean difference and 95% confidence interval were 0.02 (-0.17, 0.20). The mean postoperative hospital stays in 2 groups were 5.47 vs 5.24 days (anterior vs posterior, P = 0.02). No significant differences were identified regarding the drainage volume during the first 3 postoperative days, postoperative complications and hospitalization cost. CONCLUSIONS The comparison of clinical outcomes between anterior and posterior location of chest tube met the criteria for equivalence. For lung cancer patients undergoing video-assisted thoracoscopic surgery resection, it was free choice on anterior or posterior single-tube insertion.

To analyze the application feasibility of对“调神健脾”法针灸在终末期癌症患者临终关怀中应用的可行性进行分析。“调神健脾”法针灸调神以畅达情志、健脾以补益后天之本，应用于终末期癌症患者的临终关怀，可缓解放化疗后的不良反应、镇痛、调节情志，从而促进终末期癌症患者临终关怀工作的进展。.

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Background Larger brain volumes are often associated with more free-living physical activity (PA) in cognitively normal older adults. Yet, whether greater brain volumes are associated with more favorable (less fragmented) PA patterns, and whether this association is stronger than with total PA, remains unknown. Methods Brain magnetic resonance imaging and wrist-worn accelerometer data were collected in 301 participants (mean age = 77 [SD = 7] years, 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Linear regression models were fit to examine whether brain volumes (cc) were cross-sectionally associated with: (a) total daily PA minutes and (b) activity fragmentation (mean number of PA bouts / total PA minutes × 100). Sensitivity analyses were conducted by adjusting for counterpart PA variables (eg, fragmentation covariate included in the PA minutes model). Results Greater white matter volumes in the parietal and temporal lobes were associated with higher daily PA minutes (2.6 [SE = 1.0] and 3.8 [0.9] min/day, respectively; p < .009 for both) after adjusting for demographics, behavioral factors, medical conditions, gait speed, apolipoprotein E e4 status, and intracranial volume. Greater temporal white matter volume was associated with lower fragmentation (−0.16% [0.05], p = .003). In sensitivity analyses, observed associations between brain volumes and daily PA minutes remained significant while associations with fragmentation no longer remained significant. Conclusions Our results suggest white matter brain structure in cognitively normal older adults is associated with the total amount of PA and, to a lesser extent, the PA accumulation patterns. More work is needed to elucidate the longitudinal relationship between brain structure and function and PA patterns with aging.

Protein phosphorylation is the most significant post-translational modification for regulating cellular activities, but site-specific modulation of phosphorylation is still challenging. Using three-dimensional NMR spectra, molecular dynamics simulations, and alanine mutations, we identified that the interaction network between pT69/pS70 and R106/R109 residues prevents the phosphorylation sites from exposure to phosphatase and subsequent dephosphorylation. A Bcl-2-dephosphorylation probe, S1-6e, was designed by installing a carboxylic acid group to a Bcl-2 inhibitor. The carboxyl group competitively disrupts the interaction network between R106/R109 and pT69/pS70 and subsequently facilitates Bcl-2 dephosphorylation in living cells. As a result, S1-6e manifests a more effective apoptosis induction in pBcl-2-dependent cancer cells than other inhibitors exhibiting a similar binding affinity for Bcl-2. We believe that targeting the allosteric pathways interconnecting the core-functional domain and the phosphorylation site can be a general strategy for a rational design of site-specific dephosphorylating probes, since the allosteric pathway has been discovered in a variety of proteins.

Background: Recent studies have proven that abnormal expression of long noncoding RNAs (lncRNAs) often contributes to growth and invasion of cancer cells. The purpose of this study was to investigate the biological function and regulatory mechanism of lncRNA SOX2 overlapping transcript (SOX2-OT) in prostate cancer (PCa) progression. Materials and Methods: The expression of SOX2-OT, microRNA-452-5p (miR-452-5p), and high mobility group box 3 (HMGB3) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was performed to determine the cell cycle distribution. Western blot assay was conducted to measure the protein levels of cyclin D1, p21, p27, E-cadherin, vimentin, and N-cadherin. The interaction between miR-452-5p and SOX2-OT or HMGB3 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. The mice xenograft model was established to investigate the role of SOX2-OT in vivo. Results: SOX2-OT and HMGB3 were upregulated, whereas miR-452-5p was downregulated in PCa tissues and cells. Knockdown of SOX2-OT inhibited PCa cell growth and metastasis. MiR-452-5p could directly bind to SOX2-OT and its knockdown reversed the inhibitory effects of SOX2-OT interference on growth and metastasis of PCa cells. HMGB3 was a direct target of miR-452-5p and its knockdown weakened the promotive effects of miR-452-5p silence on growth and metastasis of PCa cells. Moreover, HMGB3 expression was inversely regulated by miR-452-5p and positively modulated by SOX2-OT. Furthermore, SOX2-OT activated the Wnt/β-catenin signaling pathway through increasing HMGB3 expression. Finally, SOX2-OT knockdown hindered tumor growth in vivo by regulating miR-452-5p/HMGB3 axis. Conclusions: SOX2-OT downregulation limited PCa cell growth and metastasis by regulating miR-452-5p/HMGB3 axis and inactivating Wnt/β-catenin signaling pathway, which might offer lncRNA-directed diagnosis and therapy for PCa.

Zinc finger E-box binding homeobox 1 (Zeb1) has been demonstrated to participate in the acquisition of the properties of cancer stem cells (CSCs). However, it is largely unknown how signals from the tumor microenvironment (TME) contribute to aberrant Zeb1 expression. Here, we show that Zeb1 depletion suppresses stemness, colonization and the phenotypic plasticity of breast cancer. Moreover, we demonstrate that, with direct cell-cell contact, TME-derived endothelial cells provide the Notch ligand Jagged1 (Jag1) to neighboring breast CSCs, leading to Notch1-dependent upregulation of Zeb1. In turn, ectopic Zeb1 in tumor cells increases VEGFA production and reciprocally induces endothelial Jag1 in a paracrine manner. Depletion of Zeb1 disrupts this positive feedback loop in the tumor perivascular niche, which eventually lessens tumor initiation and progression in vivo and in vitro. In this work, we highlight that targeting the angiocrine Jag1-Notch1-Zeb1-VEGFA loop decreases breast cancer aggressiveness and thus enhances the efficacy of antiangiogenic therapy., The transcription factor Zeb1 is known to promote tumorigenesis and stemness in breast cancer. Here the authors show that tumor endothelial Jagged1 induces activation of Notch1 signaling and increases Zeb1 expression in neighboring breast cancer stem cells, promoting tumor aggressiveness.

To analyze missed rib fractures and proper time for evaluation on CT at different ages and to determine factors that favor missed fractures. One hundred patients with rib fractures who underwent CT were classified into three groups according to their age: young, middle-aged, and elderly. CT was performed within 1 to 6 weeks after trauma. The imaging features and temporal changes of rib fractures were analyzed. At the first CT during the initial week, 638 ribs were detected with one or several fractures, overall 838 fractures were confirmed, and 6 were suspected. In the next 2–6 weeks, 47 occult rib fractures were additionally detected. The number of additionally diagnosed fractures was the highest in respectively the 3rd week among younger, 4th week in the middle-aged, and 6th week in the elderly groups. The detection of occult rib fractures was significantly delayed in the middle-aged and elderly groups compared with the young group (p < 0.05). The time to form bony callus was also significantly (p < 0.05) delayed with age, with significantly (p < 0.05) more time needed to form bony callus in the middle-aged (23.8 ± 4.5 days) and elderly (28.48 ± 5.1 days) groups than in the young group (18.0 ± 2.2 days). Most rib fractures can be detected within the first week after trauma. Detection of occult rib fractures will be delayed with increase of age, and repeated CT scanning should be appropriately postponed in patients at different ages. Trabecula, inner and outer plates, costal angle, and cartilage are the primary locations for occult and subtle fractures which should be carefully evaluated. • More rib fractures can be detected on repeated CT scans, especially for subtle and occult rib fractures. • Detection of all rib fractures helps relieve the patient’s concerns and determine the degree of personal injury for appropriate evaluation.

The aim of this research was to evaluate the resorption and osseointegration of an autogenous bone ring, which was grafted in a local vertical alveolar defect with simultaneous implant placement. Six Beagle dogs were enrolled in the study; their 4 nonadjacent mandibular premolars were extracted, and the buccal plate was removed to create bone defects in 2 of the 4 sites. Three months after extraction, Straumann implants (Ø 3.3 mm, length of 8 mm) were placed in the bone defect sites with simultaneous autogenous bone ring grafting and in the conventional extraction sites. After a 3-month healing period and a 3-month loading period, the animals were euthanized. The harvested samples were analyzed using micro-computed tomography (CT) scanning and histological analysis. From the micro-CT measurements, the average vertical bone resorption of the bone ring was 0.23 ± 0.03 mm, which was not significantly different from that around the conventional implant, 0.24 ± 0.12 mm (P > .05). The ratio of the bone volume to the total volume of the bone ring group was 91.11 ± 0.02, which was higher than that of the control group, 88.38 ± 2.34 (P < .05). From the hard tissue section, the bone rings developed fine osseointegration with the implants and the base alveolar bone. The results suggest autogenous bone ring grafting with simultaneous implant placement can survive in a local vertical bone defect with little bone resorption and good osseointegration in dogs with strict management. A bone ring graft must be compared with guided bone regeneration, and a larger and longer observation must be confirmed in clinical patients.

The ideal periprocedural anticoagulation strategy for patients being treated with a novel oral anticoagulant (NOAC) during catheter ablation (CA) for atrial fibrillation (AF) is unclear. We evaluated the safety and efficacy of using a minimally interrupted NOAC strategy versus an uninterrupted NOAC or vitamin K antagonist (VKA) strategy during AF ablation. The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled or prospective observational studies that compared a minimally interrupted NOAC strategy with an uninterrupted NOAC or VKA strategy from the time of database establishment up to December 2019. The primary endpoints were major bleeding, minor bleeding, and symptomatic thromboembolism. The secondary endpoint was silent cerebral infarction (SCI) as detected by post-ablation brain magnetic resonance imaging (MRI). A measurement of treatment effect for the endpoint was reported as pooled odds ratio (OR) with 95% confidence interval (CI). A total of 18 studies (6 randomized, 11 observational, and 1 randomized registry) with 6203 patients were included in the final analysis (47% of the patients received minimally interrupted NOAC). There was no significant difference between treatment groups regarding the risk for major bleeding (OR 1.04, 95% CI 0.69–1.57, P = 0.86, I2 = 27%). Different stratification methods did not yield significant difference regarding the risk for major bleeding. There was no difference between groups regarding the risk for minor bleeding (P = 1.00) or symptomatic thromboembolism (P = 0.26). Brain MRI results showed that both uninterrupted NOAC (OR 0.44, 95% CI 0.23–0.83, P = 0.01, I2 = 72%) and uninterrupted VKA (OR 0.48, 95% CI 0.24–0.97, P = 0.04, I2 = 36%) produced a significant reduction in the rate of SCI when compared with minimally interrupted NOAC. A periprocedural anticoagulation strategy of minimally interrupted NOAC is not superior to uninterrupted NOAC or VKA when used during AF ablation. There is evidence favoring the use of uninterrupted NOAC or VKA in terms of the risk for SCI.

Objective: To measure the validity and reliability of a Chinese version of Child Oral Health Impact Profile (COHIP) and to assess oral health-related quality of life (OHRQoL) with regard to gender, age, and cleft types in Chinese children with orofacial cleft (OFC). Design: A total of 120 patients with OFC (8-15 years old) and their parents were investigated with COHIP in the West China Hospital of Stomatology. Items were divided into oral symptoms, functional well-being, emotional well-being, school, and peer interaction subscales, and scores on all subscales were compared between and within groups. Results: The internal consistency measured by Cronbach α was satisfactory in children’s sample (0.85) and parents’ sample (0.90). The correlation between children’s and parents’ questionnaires was moderate to weak (Pearson r = 0.34), which was also supported by moderate intraclass correlation coefficients. The OHRQoL of children differed significantly from parents on the overall COHIP, functional well-being, emotional well-being, and school subscales. Older children had poor OHRQoL, functional well-being, and emotional well-being. Girls had poor emotional well-being. Children with cleft lip and palate and cleft palate performed worse on the overall COHIP, functional well-being, and school subscales. Parents, boys, and younger children had better treatment expectations and global health perceptions. Conclusion: The Chinese version of COHIP is a reliable and valid tool to assess OHRQoL in Chinese children with OFC. Parents’ reports could not replace children’s answers but add complementary information. Children’s gender, age, and cleft types should be considered in OHRQoL assessment and individual treatment plan.

Background Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. Methods A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. Results Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. Conclusions This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

Purpose. We aimed to investigate the changes of serum and cell exosome miR-205 levels in patients with prostate carcinoma and its clinical significance. Materials and Methods. Firstly, pronouncement of miR-205 in normal and prostate carcinoma tissues was analyzed by using UALCAN database. The relationship between miR-205 in tumor tissues and the pathological and clinical characteristics of patients with prostate carcinoma were analyzed. Consequently, 60 people with prostate carcinoma were collected to the Minhang Hospital from August 2016 to August 2021. Serum of patients in the two groups was collected, and RNA in serum exosomes was extracted, and qRT-PCR was used to analyze the expression of miR-205 mediated by serum exosomes. Meanwhile, the relationship among the clinical as well as pathological aspects and bodement of patients with prostate carcinoma and the pronouncement level of miR-205 mediated by exosome was compared. Next, assays like wound healing and CKK-8 were used to investigate the effects of miR-205 in exosomes extracted from prostate carcinoma on the augmentation and metastasis of prostate carcinoma. Results. The results showed that the pronouncement level of miR-205 in tissues with prostate carcinoma was significantly lower than that in normal prostate tissues. In addition, the pronouncement level of miR-205 in fluid exosome of people with prostate carcinoma and exosomes derived from the lines of prostate carcinoma was considerably less than that in serum exosomes of healthy patients and that of normal cell lines of prostate. The pronouncement level of miR-205 in fluid exosomes of people with prostate carcinoma was negatively associated with cancer phase, uncontrolled cell division in lymph nodes, distant metastasis, and PSA level at initial diagnosis. Analysis (multivariate and univariate) showed that miR-205 pronouncement was a sovereign threat cause for prognosis of prostate cancer patients. Additionally, the pronouncement and metastasis of prostate carcinoma can be restricted by the overexpression of miR-205. Conclusion. The pronouncement of miR-205 in liquid derived exosomes is correlated with the prediction of people with prostate carcinoma and may be a new marker for identification and cure of prostate carcinoma.

Hepatocellular carcinoma (HCC) is one of the malignancies with an extremely inferior prognosis in the abdominal cavity, making it essential to develop more effective biomarkers for HCC. Although GNG5 has been linked to increased patient survival in a variety of human malignancies, no evidence has been found for its involvement in the development of HCC yet. Our study first analyzed the expression and prognosis of GNG5 in HCC using The Cancer Genome Atlas database (TCGA database) with the Gene Expression Omnibus database (GEO database) and found that GNG5 has a potential oncogenic role. Based on survival analysis, the clinical importance and prognostic value of the GNG5 gene were studied. Relying on tumor Immune Estimation Resource database (TIMER database), we analyzed the correlation between the GNG5 gene and HCC Immune infiltration cells. GNG5 expression levels were significantly higher in HCC tissues compared to normal liver tissues. HCC patients with high GNG5 expression had significantly reduced overall survival time and affected multiple immune cell infiltrates. Additionally, KEGG functional enrichment analysis indicated the PI3K-Akt signaling pathway as the most promising carcinogenic pathway associated with GNG5. This is the first comprehensive revelation of GNG5 as a possible new biological marker associated with immune infiltration in HCC. Additionally, it holds promise as an emerging target for HCC immunotherapy.

A continuous flight task load can induce fatigue and lead to changes in electroencephalography (EEG). EEG microstates can reflect the activities of large-scale neural networks during mental fatigue. This exploratory experiment explored the effects of mental fatigue induced by continuous simulated flight multitasking on EEG microstate indices.Twenty-four participants performed continuous 2-hour aircraft piloting simulation while EEG were recorded. The Stanford sleepiness scale (SSS) and critical flicker fusion frequency (CFF) were measured before and after the task. Microstate analysis was applied to EEG. Four microstate classes (A-D) were identified during the pre-task, post-task, beginning, and end phases. The effects of mental fatigue were analyzed.Compared with the pre-task, the post-task had a higher global explained variance (GEV) and time parameters of class C but lower occurrence and coverage of class D. The end had a higher GEV but lower duration and coverage of class D than at the beginning. After 2 h of multitasking, the transition probability between A and D, and between B and D decreased but between A and C increased. Subjective fatigue scores were negatively correlated with occurrence and coverage of class D. Task performance was negatively correlated with duration and coverage of class C but positively correlated with duration and occurrence of class B.Time parameters and transition probability of EEG microstates can detect mental fatigue induced by continuous aircraft piloting simulation. The global brain network activation of mental fatigue can be detected by EEG microstates that can evaluate flight fatigue.

Small cell lung cancer (SCLC) is a highly aggressive cancer of the neuroendocrine system, characterized by poor differentiation, rapid growth, and poor overall survival (OS) of patients. Despite the recent advances in the treatment of SCLC recently, the 2-year survival rate of patients with the cancer is only 14-15%, occasioned by the acquired resistance to drugs and serious off-target effects. In humans, the coding region is only 2% of the total genome, and 20% of that is associated with human diseases. Beyond the coding genome are RNAs, promoters, enhancers, and other intricate elements. The non-coding regulatory regions, mainly the non-coding RNAs (ncRNAs), regulate numerous biological activities including cell proliferation, metastasis, and drug resistance. As such, they are potential diagnostic or prognostic biomarkers, and also potential therapeutic targets for SCLC. Therefore, understanding how non-coding elements regulate SCLC development and progression holds significant clinical implications. Herein, we summarized the recent discoveries on the relationship between the non-coding elements including long non-coding RNAs (lncRNA), microRNAs (miRNAs), circular RNA (circRNA), enhancers as well as promotors, and the pathogenesis of SCLC and their potential clinical applications.

Small cell lung cancer (SCLC) is a type of neuroendocrine tumor with high malignancy and poor prognosis. Besides the de novo SCLC, there is transformed SCLC, which has similar characteristics of pathological morphology, molecular characteristics, clinical manifestations and drug sensitivity. However, de novo SCLC and transformed SCLC have different pathogenesis and tumor microenvironment. SCLC transformation is one of the mechanisms of resistance to chemotherapy, immunotherapy, and targeted therapy in NSCLC. Two hypotheses have been used to explain the pathogenesis of SCLC transformation. Although SCLC transformation is not common in clinical practice, it has been repeatedly identified in many small patient series and case reports. It usually occurs in epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma after treatment with tyrosine kinase inhibitors (TKIs). SCLC transformation can also occur in anaplastic lymphoma kinase (ALK)-positive lung cancer after treatment with ALK inhibitors and in wild-type EGFR or ALK NSCLC treated with immunotherapy. Chemotherapy was previously used to treat transformed SCLC, yet it is associated with an unsatisfactory prognosis. We comprehensively review the advancements in transformed SCLC, including clinical and pathological characteristics, and the potential effective treatment after SCLC transformation, aiming to give a better understanding of transformed SCLC and provide support for clinical uses.

The precise movement of the maxilla is particularly important for orthognathic surgery, especially for patients with maxillary segmentation. In this preliminary study, the authors present a new tooth bone combined with a supporting osteotomy guide and positioning guide to guide the osteotomy and reduction of the maxilla. Through our preoperative simulation and postoperative image fusion, the authors found that the overlapping area is more than 90%. According to compare of the virtual plans and the postoperative results based on distances from the maxillary land- marks to the horizontal plane, sagittal plane, and coronal plane, the surgical error was about 2mm. Our T-shaped guide provides a reliable method for patients with maxillary segmental osteotomy, which may be a useful alternative to the intermediate.