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Background Osteoarthritis-related insomnia is the most common form of comorbid insomnia among older Americans. A randomized clinical trial found that six sessions of telephone-delivered cognitive behavioral therapy for insomnia (CBT-I) improved sleep outcomes in this population. Using these data, we evaluated the incremental cost-effectiveness of CBT-I from a healthcare sector perspective. Methods The study was based on 325 community-dwelling older adults with insomnia and osteoarthritis pain enrolled with Kaiser Permanente of Washington State. We measured quality-adjusted life years (QALYs) using the EuroQol 5-dimension scale. Arthritis-specific quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Insomnia-specific quality of life was measured using the Insomnia Severity Index (ISI) and nights without clinical insomnia (i.e., "insomnia-free nights"). Total healthcare costs included intervention and healthcare utilization costs. Results Over the 12 months after randomization, CBT-I improved ISI and WOMAC by -2.6 points (95% CI: -2.9 to -2.4) and -2.6 points (95% CI: -3.4 to -1.8), respectively. The ISI improvement translated into 89 additional insomnia-free nights (95% CI: 79 to 98) over the 12 months. CBT-I did not significantly reduce total healthcare costs (-$1072 [95% CI: -$1968 to $92]). Improvements in condition-specific measures were not reflected in QALYs gained (-0.01 [95% CI: -0.01 to 0.01]); at a willingness-to-pay of $150,000 per QALY, CBT-I resulted in a positive net monetary benefit of $369 with substantial uncertainty (95% CI: -$1737 to $2270). Conclusion CBT-I improved sleep and arthritis function without increasing costs. These findings support the consideration of telephone CBT-I for treating insomnia among older adults with comorbid OA. Our findings also suggest potential limitations of the general quality of life measures in assessing interventions designed to improve sleep and arthritis outcomes.

Objective: To present our preliminary experiences of robot-assisted laparoscopic radical or partial cystectomy for bladder/prostate rhabdomyosarcoma (B/P RMS) in children. Methods: A retrospective study was conducted with children who underwent robot-assisted laparoscopic surgery for B/P RMS between July 2018 and March 2020 under the approval of IRB of our center. The patient characteristics, tumor position, perioperative information, short time oncologic survival outcomes, and urinary function were recorded and evaluated. Results: We identified eight children who underwent robot-assisted laparoscopic surgery for B/P RMS. Partial cystectomy was performed on all, but one, patients, who underwent radical cystectomy and sigmoid neobladder reconstruction. Preoperative chemotherapy was administered to all eight patients, while preoperative radiotherapy was conducted in three cases, including one patient with a history of pelvic RMS. Unilateral/bilateral ureteral reimplantation was done in four cases in which the patients' ureteral orifices were involved. The mean follow-up time was 13.3 months, and no local recurrence or metastasis was observed. No patient experienced urinary incontinence eventually. Conclusion: Robot-assisted laparoscopic resection for bladder RMS in children is safe and feasible. Preoperative radiotherapy could decrease the tumor volume so that the membranous urethra could be preserved for as long as possible. The oncologic efficacy and the overall survival rate require further investigation and longer follow-up.

Background The aims of this study were to identify risk factors for significant fibrosis (SF) by assessing physical and laboratory parameters and develop and validate a clinical score and nomogram for the prediction of SF in patients with nonalcoholic fatty liver disease (NAFLD). Methods This retrospective study included 225 patients with histologically confirmed NAFLD who were divided into two cohorts using 10-fold cross validation for model training and validation. The clinical score and nomogram were used to predict the NAFLD outcome. Results The model for predicting SF (stage ≥ 2) including the free T4/free T3 ratio, low-density lipoprotein cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), percentage of appendicular skeletal muscle mass and aspartate aminotransferase (AST) level in the training and validation cohorts yielded an area under the receiver operator characteristic curve (AUROC) of 0.79 and 0.78, respectively. The AUROC of the combined clinical score for the prediction of SF was 0.82 (95% CI, 0.75–0.89) at a cutoff value of 3 points, with a sensitivity (SE) of 77.19%, specificity (SP) of 82.88%, positive predictive value (PPV) of 63.77%, and negative predictive value (NPV) of 90.30%. The nomogram had good performance in quantitatively predicting the risk probability of SF. Conclusion Our study showed that a noninvasive clinical scoring system using easily available physical and laboratory variables can identify patients with NAFLD with or without SF with a high degree of accuracy. Application of this system may decrease the need for staging liver biopsy specimens and allow early identification and intervention in these high-risk patients.

Elevated levels of reactive oxygen species (ROS) are implicated in the onset and progression of many diseases, e.g., virus infection, ischemic stroke and neurodegenerative diseases. ROS-scavenging nanomaterials have attracted particular interest. Here, we report the development of a natural protein nanocage named Dps for in vitro and in vivo antioxidant treatment by inhibiting the Fenton reaction, a critical step in ROS generation and interconversion. Systematic surface engineering enabled cell penetration, good colloidal stability, and facile purification of Dps. With its intrinsic ferroxidase activity consuming both H2O2 and Fe2+, Dps not only protects human cells from oxidative stress but also effectively alleviates ROS-induced inflammation in a mouse dermatitis model. The protection is triggered by elevated H2O2 and thereby, in principle, avoids ROS imbalances. Thus, Dps has potential as a new bionano platform for different purposes, such as antiaging, anti-inflammation and cosmetics.

Non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) patients with normal left ventricular (LV) ejection fraction (LVEF) and wall motion require a non-invasive tool to detect LV risk areas. This study utilized non-invasive LV pressure–strain loops to evaluate territorial myocardial work efficiency (WE) for identifying obstructive coronary artery stenosis, in patients with non-obstructive or obstructive coronary artery stenosis NSTE-ACS, the latter with or without occlusion. Global and territorial longitudinal strain (LS) analyses were performed via speckle-tracking imaging before coronary angiography. LV pressure–strain loops estimated global and territorial myocardial work index (MWI), constructive work (CW), wasted work (WW), and WE. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of independent parameters to detect obstructive coronary artery stenosis. Compared with non-obstructive, obstructive coronary artery stenosis showed significantly lower global and territorial LS, MWI, CW, and WE, and higher WW. Territorial LS, MWI, CW, and WE were significantly worse in territories of coronary occlusion. Territorial WE was the best parameter for predicting obstructive coronary artery stenosis (AUC 0.80, cutoff

Purpose This study aimed to establish a nomogram to predict the long‐term overall survival (OS) for patients with penile squamous cell carcinoma (PSCC). Method The PSCC patients receiving regional lymph node dissection (RLND) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The dataset of all eligible patients were used to develop the predictive model. The significant independent predictors were identified through Cox regression modeling based on the Bayesian information criterion and then incorporated into a nomogram to predicted 1‐, 3‐, and 5‐year OS. Internal validation was performed using the bootstrap resampling method. The model performance was evaluated using Harrell's concordance index (C‐index), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). Results Totally, 384 eligible PSCC patients were enrolled from the SEER database. A nomogram for OS prediction was developed, in which three clinical variables significantly associated with OS were integrated, including age, N classification, and log odds of positive lymph nodes (LODDS). The C‐index of the nomogram (0.746, 95% CI: 0.702‐0.790) was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.692, 95% CI: 0.646‐0.738, P = .020). The bootstrap optimism‐corrected C‐index for the nomogram was 0.739 (95% CI: 0.690‐0.784). The bias‐corrected calibration plots showed the predicted risks were in good accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram compared with the AJCC staging system. Conclusion We successfully constructed a simple and reliable nomogram for OS prediction among PSCC patients receiving RLND, which would be beneficial to clinical trial design, patient counseling, and therapeutic modality selection., In this study, we successfully constructed a simple and reliable nomogram for survival prediction among patients with penile squamous cell carcinoma. Three clinical variables were integrated into the model, including age, N classification, and log odds of positive lymph nodes. Compared to the AJCC staging system, the established nomogram exhibited superior predictive ability and clinical use.

Purpose Social contagion among physicians may affect the dissemination of innovative and high-value cancer care. We applied social contagion theory to investigate the role of physician peer influence on the use of short courses of external beam radiation therapy (EBRT) for patients with breast cancer. Methods and Materials Using a cohort of Medicare beneficiaries with breast cancer, we constructed physician peer groups based on patient-sharing relationships. Outcomes were a patient’s receipt of (1) moderately hypofractionated adjuvant EBRT after breast-conserving surgery and (2) short-course palliative EBRT for bone metastases. Using a longitudinal design, we used mixed-effects logistic regression to examine the association between physician peer group rate of short-course EBRT in 2011 to 2012 (T1) and patients’ receipt of short-course EBRT in 2013 to 2014 (T2). Results During T2, a total of 17,248 patients received adjuvant therapy (32.3% moderately hypofractionated) from 3235 physicians in 1202 physician peer groups. Compared with patients treated within peer groups in which no moderately hypofractionated adjuvant EBRT was used in T1, patients treated by a physician in a peer group with higher T1 use of moderately hypofractionated adjuvant EBRT were more likely to receive moderately hypofractionated adjuvant EBRT in T2 (adjusted odds ratio = 2.03; 95% confidence interval, 1.62-2.54, vs adjusted odds ratio = 2.61; 95% confidence interval, 2.04-3.35, for peer groups where 21%-46% and 47%-100% of radiation oncologists used moderately hypofractionated adjuvant EBRT in T1, respectively, compared with peer groups with no use of moderately hypofractionated adjuvant EBRT). In contrast, there was no significant relationship between T1 peer group use and T2 receipt of short-course palliative EBRT for bone metastases. Conclusions Physician peer groups significantly influenced use of short-course EBRT in adjuvant therapy but not in palliative therapy for patients with breast cancer.

Background: Toxoplasmosis is an extremely rare disease that occurs in the hosts contact with cat and dog frequently. Most human acute infections go unnoticed in immunocompetent individuals, and gradually transformed into chronic infection. However, while host immunity significantly waned, the risk of reactivation of chronic toxoplasma infection is greatly increased. Reactivation of latent toxoplasmic infection often presents with fever, leukopenia, thrombocytopenia, neurological signs and pneumonia. However, for the non-specific clinical and biological signs and its fetal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. Case Presenation: We report a case hospitalized for a week history of cough, anorexia and fatigue with nasal bleeding for a day. After hospitalization, broad-spectrum antibiotherapy was started without a clear diagnosis of infection. Then the patient did a lot of investigations to search the cause of infection, but there were no positive findings. However, an unexpected discovery was detected from peripheral blood smears, shows 1 - 3 μm in diameter, scattered, short and bow like microorganisms on Day 39 of hospitalization. Combined with the medical history and clinical manifestation, toxoplasmosis was diagnosed finally. Unfortunately, secondary hemophagocytic syndrome (HPS) was diagnosed only two days after targeted anti-infection therapy, and the patient died on Day 45 of hospitalization. Conclusions: Patient with unexplained long-term fever and neurological symptoms, interstitial pneumonitis or myocarditis, toxoplasmosis should be positively considered. Only early diagnosis and treatment can increase the possibility of a successful cure and avoid other secondary diseases.

Sepsis commonly progresses to disseminated intravascular coagulation and induces the activation of heparanase (HPA) and the shedding of endothelial glycocalyx constituents, including syndecan-1 (SDC-1) and heparan sulphate (HS). However, the degradation of glycocalyx and its association with coagulation disorders remains undetermined. The present study aimed to evaluate the effect of unfractionated heparin (UFH) and N-acetylheparin (NAH), which is a non-anticoagulant heparin derivative, on endothelial glycocalyx and coagulation function in a lipopolysaccharide (LPS)-induced sepsis rat model, and to compare the differences observed in coagulation function between UFH and NAH. Experimental rats were randomly assigned to four groups: Control; LPS; UFH + LPS; and NAH + LPS. Rats were administered UFH or NAH and subsequently, ~1 min later, administered LPS (10 mg/kg; intravenous). The blood and lung tissues of rats were collected 0.5, 2 and 6 h after LPS injection, and were used for subsequent analysis. The results demonstrated that HPA activity and SDC-1 and HS levels increased, and this increase was associated with inflammatory cytokines and coagulation/fibrinolysis markers in the sepsis rat model. Histopathological examination was performed, and the lung injury score and lung wet/dry ratio indicated that UFH and NAH also significantly improved lung tissue injury. The results of the ELISA analysis demonstrated that UFH and NAH treatment: i) significantly decreased the levels of inflammatory cytokines including tumor necrosis factor-α and interleukin-6; ii) inhibited HPA activity and protected the integrity of the glycocalyx, which was identified by decreased HS and SDC-1 levels; and iii) decreased the levels of prothrombin fragment 1+2, thrombin-antithrombin complex, and plasminogen activator inhibitor-1 and increased the levels of fibrinogen and antithrombin-III. Preconditioning with UFH decreased the plasma activated partial thromboplastin time. These results indicated that UFH and NAH may alleviate sepsis-induced coagulopathy, and this effect may have been due to an inhibition of HPA activity and decrease in the shedding of the endothelial glycocalyx.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis. The disease is characterized by strong infectivity, high morbidity, and high mortality. It is still spreading in some countries. Microbiota and their metabolites affect human physiological health and diseases by participating in host digestion and nutrition, promoting metabolic function, and regulating the immune system. Studies have shown that human microecology is associated with many diseases, including COVID-19. In this research, we first reviewed the microbial characteristics of COVID-19 from the aspects of gut microbiome, lung microbime, and oral microbiome. We found that significant changes take place in both the gut microbiome and airway microbiome in patients with COVID-19 and are characterized by an increase in conditional pathogenic bacteria and a decrease in beneficial bacteria. Then, we summarized the possible microecological mechanisms involved in the progression of COVID-19. Intestinal microecological disorders in individuals may be involved in the occurrence and development of COVID-19 in the host through interaction with ACE2, mitochondria, and the lung-gut axis. In addition, fecal bacteria transplantation (FMT), prebiotics, and probiotics may play a positive role in the treatment of COVID-19 and reduce the fatal consequences of the disease.

Background The germinal center B‐cell (GCB) and activated B‐cell (ABC) subtypes of diffuse large B‐cell lymphoma (DLBCL) have a significant difference in prognosis. This study aimed to identify potential hub genes, and key pathways involved in them. Methods Databases including Gene Expression Omnibus (GEO), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING were accessed to obtain potential crucial genes and key pathways associated with the GCB and ABC. Then qRT‐PCR and Western blot experiments were performed to verify the most clinically significant gene and pathway. Results Three cohort datasets from the GEO database were analyzed, including 195 GCB and 169 ABC samples. We identified 1113 differentially expressed genes (DEGs) between the GCB and ABC subtypes. The DEGs were mainly enriched in biological processes (BP). The KEGG analysis showed enrichment in cell cycle and Wnt signaling pathways. We selected the top 10 genes using the STRING database and Cytoscape software. We used 5 calculation methods of the cytoHubba plugin, and found 3 central genes (IL‐10, CD44, CCND2). CCND2 was significantly related to the prognosis of DLBCL patients. Besides, our experimental results demonstrated a significantly higher expression of CCND2 in the ABC‐type cell line than in the GCB‐type; it was proportional to the expression of key proteins in the Wnt signaling pathway. Conclusion CCND2 overexpression and Wnt pathway activation might be the main reasons for the poor prognosis of ABC‐DLBCL., The study revealed that CCND2 overexpression and Wnt pathway activation may be factors of the poor prognosis of ABC‐subtype DLBCL by integrative bioinformatic analysis and basic experiments.

In a primary care population of 327 older adults (age 60+) with chronic osteoarthritis (OA) pain and insomnia, we examined the relationship between short-term improvement in sleep or pain and long-term sleep, pain, depression, and fatigue by secondary analyses of randomized controlled trial data. Study participants, regardless of trial arm, were classified as Sleep or Pain Improvers with ≥30% baseline to 2-month reduction on the Insomnia Severity Index or the Brief Pain Inventory, respectively, or Sleep or Pain Non-Improvers. After controlling for trial arm and potential confounders, both Sleep and Pain Improvers showed significant (p < .01) sustained improvements across 12 months compared to respective Non-Improvers for the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Brief Pain Inventory-short form (total, Interference, and Severity subscales), Patient Health Questionnaire, and Flinders Fatigue Scale. The effect sizes (Cohen’s f2) for the sustained benefits in both Sleep and Pain Improvers compared to their respective Non-Improvers for all variables were small ( Trial Registration: OsteoArthritis and Therapy for Sleep (OATS) NCT02946957: https://clinicaltrials.gov/ct2/show/NCT02946957.

Additional proximal fixation for growing rods in early-onset scoliosis (EOS) may offer a more effective and safer option for severe scoliosis patients with hyper-kyphosis. Here, we compared the outcomes of EOS patients treated with growing rods in which 6 proximal anchor points on 3 vertebrae were used vs. 4 proximal anchor points on 2 vertebrae. The records of patients with EOS treated surgically from January 2016 to December 2017 were retrospectively reviewed. In the Proximal 4 group, 2 vertebral bodies were anchored proximally with 4 anchor points; in the Proximal 6 group, 3 vertebral bodies were anchored proximally with 6 anchor points. Forty-two patients (mean age 5.11 ± 1.93 years) were included; 22 Proximal 4 group, 20 Proximal 6 group. Mean follow-up was 40.86 ± 13.49 months. The decrease in main curve Cobb angle postoperatively was significantly greater in the Proximal 6 group (33.22° vs. 19.08°) (P0.05). Cobb thoracic kyphosis (TK) was significantly decreased postoperatively in the Proximal 6 group (mean 20.70°); no significant decrease occurred in the Proximal 4 group. The main curve Cobb angle decrease at last follow-up was significantly greater in the Proximal 6 group (37.84° vs. 24.23°) (P0.05). Cobb TK was significantly decreased at last follow-up in the Proximal 6 group (mean 25.17°, P0.05); no significant decrease occurred in the Proximal 4 group. Instrument complications were lower in the Proximal 6 group (15.00% vs. 45.45%) (P0.05). No proximal junctional kyphosis was noted. Fixing 3 proximal vertebral bodies with 6 anchors improves radiographic outcomes of EOS treated with growing rods, and has a lower rate of screw pull-out.

PURPOSE Preoperative breast MRI is used to evaluate for additional cancer and extent of disease for newly diagnosed breast cancer, yet benefits and harms of preoperative MRI are not well-documented. We examined whether preoperative MRI yields additional biopsy and cancer detection by extent of breast density. METHODS We followed women in the Breast Cancer Surveillance Consortium with an incident breast cancer diagnosed from 2005 to 2017. We quantified breast biopsies and cancers detected within 6 months of diagnosis by preoperative breast MRI receipt, overall and by breast density, accounting for MRI selection bias using inverse probability weighted logistic regression. RESULTS Among 19,324 women with newly diagnosed breast cancer, 28% had preoperative MRI, 11% additional biopsy, and 5% additional cancer detected. Four times as many women with preoperative MRI underwent additional biopsy compared to women without MRI (22.6% v. 5.1%). Additional biopsy rates with preoperative MRI increased with increasing breast density (27.4% for extremely dense compared to 16.2% for almost entirely fatty breasts). Rates of additional cancer detection were almost four times higher for women with v. without MRI (9.9% v. 2.6%). Conditional on additional biopsy, age-adjusted rates of additional cancer detection were lowest among women with extremely dense breasts, regardless of imaging modality (with MRI: 35.0%; 95% CI 27.0-43.0%; without MRI: 45.1%; 95% CI 32.6-57.5%). CONCLUSION For women with dense breasts, preoperative MRI was associated with much higher biopsy rates, without concomitant higher cancer detection. Preoperative MRI may be considered for some women, but selecting women based on breast density is not supported by evidence. TRIAL REGISTRATION ClinicalTrials.gov: NCT02980848; registered 2017.

Tumor targeting with nanoparticles is a promising strategy for cancer diagnosis and treatment, especially for drug delivery to solid tumors. Previous studies mainly focused on nanoparticle design to improve their targeting efficiency, but few have investigated the impact of tumor progression stages on the targeting efficiency. Here, we used PEGylated viral nanoparticles (VNPs) of bacteriophage P22 to explore the relationship between targeting efficiency and tumor progression stages using a colorectal cancer model. We found an 8.1-fold increase in the accumulation of P22 VNPs systematically injected 7 days after tumor inoculation compared with those injected 21 days after tumor inoculation. Most tumor-targeted P22 VNPs were concentrated in tumor-associated macrophages in the tumor blood vessels, the density of which decreased with the progression of tumors. These results reveal that the tumor targeting efficiency of P22 VNPs decreased with tumor progression. These findings provide valuable information for not only the understanding of controversial observations regarding targeted cancer therapy in experimental and clinical studies but also the design of nanoparticle-based tumor targeting probes or therapeutics.

Introduction The left atrial (LA) strain and strain rate are sensitive indicators of LA function. However, they are not widely used for the evaluation of pregnant women with metabolic diseases. The aim of this study was to assess the LA strain and strain rate of pregnant women with clustering of metabolic risk factors and to explore its prognostic effect on adverse pregnancy outcomes. Materials and methods Sixty-three pregnant women with a clustering of metabolic risk factors (CMR group), fifty-seven women with pregnancy-induced hypertension (PIH group), fifty-seven women with gestational diabetes mellitus (GDM group), and fifty matched healthy pregnant women (control group) were retrospectively evaluated. LA function was evaluated with two-dimensional speckle-tracking imaging. Iatrogenic preterm delivery caused by severe preeclampsia, placental abruption, and fetal distress was regarded as the primary adverse outcome. Results The CMR group showed the lowest LA strain during reservoir phase (LASr), strain during contraction phase (LASct) and peak strain rate during conduit phase (pLASRcd) among the three groups (P P Conclusions LA mechanical function in pregnant women with metabolic aggregation is deteriorated. An LASr value of 38.35% or less may indicate the occurrence of adverse pregnancy outcomes.

Background Dual-energy computed tomography (DECT) can differentiate iodine from other materials through the material decomposition technique. The purpose of this study was to compare the diagnostic performance of DECT-derived iodine concentration (mg/ml) with conventional enhancement measurements (HU), in detecting left atrial appendage (LAA) thrombi and differentiating thrombi from circulatory stasis in atrial fibrillation (AF) patients referred for catheter ablation. Methods Consecutive patients were prospectively recruited and scanned using a third-generation dual-source CT system in dual-energy mode. Regions of interest were placed inside the filling defect in the LAA and ascending aorta (AA) of the same sections, to determine iodine concentration and the LAA/AA HU ratio. The diagnostic performance of iodine concentration and LAA/AA HU ratios were compared using transesophageal echocardiography (TEE) as the reference standard. Results Among 302 patients, 10 thrombi and 27 cases with spontaneous echo contrast (SEC) were detected by TEE. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of iodine concentration were superior to those of LAA/AA HU ratios (iodine concentration: 99.7%, 100%, 99.7%, 90.9%, and 100% vs. LAA/AA HU ratios: 96.0%, 100%, 95.9%, 45.5%, and 100%) in detecting LAA thrombi. The area under the receiver operating characteristic curve of iodine concentration (0.996; 0.898–1.000) was significantly larger than that of the LAA/AA HU ratio (0.881; 0.733–0.964) in differentiating thrombi from circulatory stasis (p Conclusions DECT-derived iodine concentration was associated with improved diagnostic accuracy compared with conventional enhancement measurements in detecting LAA thrombi and differentiating thrombi from circulatory stasis in AF patients.

Population level survival of patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) is inferior to clinical trials. Using SEER-Medicare data, we identified 2,086 MDS patients diagnosed in 2004–13, aged ≥66 years at diagnosis, and receiving ≥1 HMA cycle. We used multivariate logistic regression and Cox proportional hazards models to assess the impact of provider experience on persistent HMA therapy and overall survival (OS), respectively. Median number of HMA cycles was 4 and median OS was 10 months. 32% of patients were treated by providers with ≥1 prior HMA initiation in the last 2 years and were more likely to receive ≥4 cycles of HMA therapy (OR=1.29, 95%-CI: 1.06–1.57; P=.01). No significant association was found between MDS or HMA initiation volume and survival. In conclusion, while HMA initiation volume was associated with persistent HMA treatment, neither MDS nor HMA initiation volumes were associated with OS in older MDS patients.

Primary cardiac tumors are rare, but papillary fibroelastoma (PFE) is reportedly the most common form, which usually occurs on the left-side valves of the heart. However, PFE involving the tricuspid and pulmonary valves has also been documented. Although PFE is benign and seldom associated with valvular dysfunction, the associated embolic complications may lead to serious consequences. Most patients with PFE lack specific clinical symptoms and the diagnosis is incidental. Surgical resection is the mainstay treatment for PFE in order to prevent the occurrence of embolic complications. In this report, we present a case of a rare asymptomatic PFE of the pulmonary valve, which was incidentally noted during a routine examination with transthoracic echocardiography (TEE). There was neither valvular dysfunction nor hemodynamic change. The PFE was surgically removed, and the diagnosis was further confirmed with histopathology.

Background The suicide risk was higher in kidney cancer patients than in the general population. The purpose of this study was to characterize the suicide rates among kidney cancer patients and to identify the potential risk factors associated with suicide from the Surveillance, Epidemiology, and End Results (SEER) database. Methods Kidney cancer patients were identified from the SEER database during 1973‐2015. Suicide rates and standardized mortality ratios (SMRs) of this population were calculated, and the US general population during 1981‐2015 was chosen as a reference. Univariable and multivariable Cox regression were performed to find out potential risk factors of suicide. Results There were 207 suicides identified among 171 819 individuals with kidney cancer observed for 948 272 person‐years. The suicide rate was 21.83 per 100 000 person‐years, and SMR was 1.83 (95% CI: 1.59‐2.10). On Cox regression, diagnosis in early years (1973‐1982 vs 2003‐2015, HR: 2.03, 95% CI: 1.01‐4.11, P = 0.048; 1983‐1992 vs 2003‐2015, HR: 1.99, 95% CI: 1.18‐3.35, P = 0.010), male sex (vs female sex, HR: 4.43, 95% CI: 2.95‐6.65, P

INTRODUCTION: With no evidence to support extended radiation courses for the palliation of bone metastases, multiple guidelines were issued discouraging its use. We assessed contemporary use and cost of prolonged palliative radiotherapy in Medicare beneficiaries with bone metastases from breast cancer. METHODS: We conducted a retrospective, longitudinal study of palliative radiotherapy use among fee-for-service Medicare beneficiaries with bone metastasis from breast cancer who underwent palliative radiotherapy during 2011–2014. Patients were categorized according to the number of days (‘fractions’) on which they received palliative radiotherapy: 1, 2–10, 11–19, or 20–30. We examined the association of clinical, demographic, and provider characteristics with the use of extended (≥11 fractions) or very extended (≥20 fractions) fractionation with logistic regression models. We also compared the cost of different fractionation schemes from the payer perspective. RESULTS: Of the 7,547 patients in the sample (mean age 71 years), 3,084 (40.8%) received extended fractionation. The proportion of patients receiving 11–19 (34.7% in 2011 and 28.1% in 2014, trend p

Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote the progression of chronic cholestatic liver diseases. We previously reported that cholangiocyte-derived exosomal long noncoding RNA-H19 (lncRNA-H19) plays a critical role in promoting cholestatic liver injury. However, it remains unclear whether cholangiocyte-derived lncRNA-H19 regulates HSC activation, which is the major focus of this study. Both bile duct ligation (BDL) and Mdr2 knockout (Mdr2-/- ) mouse models were used. Wild-type and H19maternalΔExon1/+ (H19KO) mice were subjected to BDL. Mdr2-/- H19maternalΔExon1/+ (DKO) mice were generated. Exosomes isolated from cultured mouse and human cholangiocytes or mouse serum were used for in vivo transplantation and in vitro studies. Fluorescence-labeled exosomes and flow cytometry were used to monitor exosome uptake by hepatic cells. Collagen gel contraction and bromodeoxyuridine assays were used to determine the effect of exosomal-H19 on HSC activation and proliferation. Mouse and human primary sclerosing cholangitis (PSC)/primary biliary cholangitis (PBC) liver samples were analyzed by real-time PCR, western blot analysis, histology, and immunohistochemistry. The results demonstrated that hepatic H19 level was closely correlated with the severity of liver fibrosis in both mouse models and human patients with PSC and PBC. H19 deficiency significantly protected mice from liver fibrosis in BDL and Mdr2-/- mice. Transplanted cholangiocyte-derived H19-enriched exosomes were rapidly and preferentially taken up by HSCs and HSC-derived fibroblasts, and promoted liver fibrosis in BDL-H19KO mice and DKO mice. H19-enriched exosomes enhanced transdifferentiation of cultured mouse primary HSCs and promoted proliferation and matrix formation in HSC-derived fibroblasts. Conclusion: Cholangiocyte-derived exosomal H19 plays a critical role in the progression of cholestatic liver fibrosis by promoting HSC differentiation and activation and represents a potential diagnostic biomarker and therapeutic target for cholangiopathies.

ObjectiveThis study aimed to evaluate outcomes of the sequential one-stage combined procedure for treating bilateral developmental dysplasia of the hip (DDH) that was diagnosed after walking age.MethodsThirty-five patients (70 hips) with late-presenting bilateral DDH were treated with the sequential one-stage combined procedure. Hips were reclassified according to the operative time and divided into the first and the second operated hips. The outcomes were compared clinically and radiographically between the two sides preoperatively and postoperatively.ResultsThe mean interval time between the two procedures was 5.9 months (range: 2–9 months). The first operated hip achieved better results than did the second operated hip. A total of 68.6% (24/35) of the patients in our series had an asymmetric outcome.ConclusionsThe sequential one-stage combined procedure is a challenge, but a reasonable alternative surgery for bilateral DDH in children after walking age. An asymmetric outcome is a special complication of this procedure.

This study establishes a dynamic model of a new brake system with two-layer structure to explore the mechanism of vibration and noise reduction of a brake pad with new structure. The model is used to analyze the effects of parameters of the double-layer pad on the stability and stick-slip vibration characteristics of the brake system. The stability of the brake system is optimized by brake parameters with respect to the stability diagram of brake pressure under a relatively wide range. System vibration modes can be changed from period-doubling bifurcation to chaos based on the variation of brake pressure and the parameters of double-layer pad via numerical analysis. The chaotic vibration region is optimized in this study using the correlation coefficient, which consists of friction-layer pad mass mb2 and connection stiffness k2. Results show that the range of chaotic vibration region can be reduced when the friction-layer pad mass and connection stiffness are large.

OBJECTIVES Right ventricular (RV) contractile reserve reflects the ability of RV to accommodate the increased afterload and may play an essential role in the evaluation of precapillary pulmonary hypertension (PH). This study aimed to assess RV contractile reserve based on exercise stress echocardiography (ESE) and to determine the echocardiographic determinants of exercise capacity in patients with precapillary PH. METHODS A total of 31 patients with precapillary PH and 15 age- and sex-matched healthy control subjects were prospectively recruited. All subjects underwent ESE to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. Patients with precapillary PH also underwent cardiopulmonary exercise test (CPET), and data pertaining to peak oxygen uptake (peak VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) were collected. RESULTS Right ventricular contractile reserve including change in tricuspid annular plane systolic excursion (∆TAPSE), change in RV fractional area change (∆RVFAC), and change in Doppler-derived tricuspid lateral annular peak systolic velocity (∆S') was significantly depressed in precapillary PH patients compared with control subjects (P

The present study investigated the changes of biventricular mechanics at rest and during exercise and examined the association between exercise capacity and biventricular mechanics and functional reserve in nonobstructive hypertrophic cardiomyopathy (NHCM) patients. A total of 50 NHCM patients and 25 controls were consecutively recruited for this study. Using echocardiography and two-dimensional speckle-tracking imaging, an experienced echocardiographer determined the following indices: RV free wall longitudinal strain (RVFWLS), LV global longitudinal strain (LVGLS), strain rate (SR), and functional reserve of strain values. We also investigated the relationships between biventricular mechanics and exercise capacity using metabolic equivalents (METs). NHCM patients had lower RVFWLS, LVGLS, systolic SR, early diastolic SR, and systolic and diastolic reserve during exercise compared to controls. An association of biventricular mechanics (LVGLS, RVFWLS) with exercise capacity at rest and during exercise was established. Multivariable logistic regression revealed that RVFWLS and LVE/e' during exercise (RVFWLS-exe, E/e'-exe) were independent predictors of exercise intolerance. Receiver operating characteristic curve analysis indicated that LVE/e'-exe had a higher area under the curve for predicting exercise intolerance in NHCM patients. In hierarchical analysis, RVFWLS-exe provided an incremental predictive value of exercise intolerance over LVGLS during exercise (LVGLS-exe) and LVE/e'-exe. LVE/e'-exe also changed incrementally compared to LVGLS-exe and RVFWLS-exe. NHCM patients have decreased biventricular mechanics at rest and during exercise and impaired biventricular functional reserve, and biventricular mechanics are associated with functional capacity. We propose that simultaneous evaluation of biventricular function should provide incremental predictive value for exercise intolerance.

Intrauterine inflammation generates inflammatory mediators that damage the developing bronchoalveolar epithelium, resulting in neonatal lung injury. Lung fluid transport disorders are the main reasons for the development of pulmonary edema, an important pathology of lung injury. Previous studies suggested that epithelial sodium channels (ENaCs) play an important role in lung fluid transport. Here, we investigated whether changes in the expression of ENaCs were observed when neonatal rat lung injury was induced by maternal exposure to endotoxin. We also examined the therapeutic effect of terbutaline nebulizer inhalation on this injury. The results showed that maternal exposure to endotoxin increased the levels of TNF‐α and IL‐1β in bronchoalveolar lavage fluid, suppressed α‐, β‐, γ‐ENaC in the neonatal rat lung, and resulted in the formation of pulmonary edema on postnatal days 1 and 7. Terbutaline up‐regulated the expression of β‐ and γ‐ENaC in the distal lung after 7 days of treatment. The potential signal molecules cAMP, PKA, and CREB expressions were increased after terbutaline treatment. In summary, maternal exposure to endotoxin decreased the expression of ENaCs in neonatal rats which, in turn, may exacerbate pulmonary edema. Inhalation of the β2‐adrenergic receptor agonist terbutaline improved lung liquid clearance. By increasing the expression of sodium ion channels, the effective removal of alveolar fluid provides a new way for the prevention and treatment of neonatal lung injury.

Background Reduced metabolic equivalents (METs) are an indicator of exercise intolerance, which predicts poor prognosis in hypertrophic cardiomyopathy (HCM) patients. We sought to evaluate the changes in left ventricular (LV) mechanics and functional reserves, as well as their association with functional capacity in HCM patients. Methods Seventy HCM patients and thirty controls were included in this study. LV mechanics were evaluated at rest and during exercise by echocardiography and two-dimensional speckle-tracking imaging to obtain parameters of functional reserve, LV global longitudinal strain (LVGLS), strain rate (SR), and circumferential strain. Results Hypertrophic cardiomyopathy (HCM) patients had lower LVGLS, systolic SR, early and late diastolic SR at rest and during exercise, and reduced absolute and relative systolic and diastolic reserve compared to controls. LV circumferential strain was significantly higher at rest but lower during exercise in HCM patients. Exercise capacity was markedly reduced in HCM patients, and peak exercise LVGLS (LVGLS-exe) significantly correlated with exercise capacity. Multivariate regression analyses showed that LVGLS-exe, LV filling pressure during exercise (E/e'-exe), and LV mass index (LVMI) were independent predictors of exercise capacity. Moreover, LVGLS-exe displayed incremental predictive value over E/e'-exe and LVMI for exercise intolerance. Receiver operating characteristic curve analysis showed LVGLS-exe had optimal accuracy for predicting exercise intolerance in HCM patients. Conclusions Hypertrophic cardiomyopathy (HCM) patients have reduced LV mechanics at rest and during exercise and impaired mechanical reserve. LVGLS-exe is associated with exercise capacity and is an optimal predictive value for reduced exercise capacity in HCM patients.

Relapsed diffuse large B-cell lymphoma (DLBCL) is a disease with a poor prognosis. Recent clinical trials results showed chimeric antigen receptor (CAR) T cell therapy has a promising role in treating relapsed DLBCL. Unfortunately, patients with extranodal lesions respond poorly to CAR-T cells administered intravenously. Herein, we evaluated the efficacy and safety of a new treatment strategy of CAR-T cells, combining intravenous infusion with local injection of CAR-T cells, in a relapsed DLBCL patient with extranodal lesions. The patient achieved durable remission and without severe adverse effects after CAR-T cells treatment. During the follow-up period of one year, the patient remained in good condition. In conclusion, combining intravenous injection with a local injection for CAR-T cell is a feasible strategy for relapsed DLBCL patients with extranodal lesions.

Objective: To present our primary experience of robotic-assisted laparoscopic pyeloplasty (RALP) for severe ureteropelvis junction obstruction (UPJO) infants under 3 months.Methods: We performed a retrospective study of 9 infants under 3 months who underwent RALP for severe UPJO between April 2017 and March 2019 in our center. The severe UPJO was defined as infants with severe hydronephrosis (Society of Fetal Urology grades III or IV, anteroposterior diameter >3 cm or split renal function 20 min) involving bilateral, solitary kidney, or contralateral renal hypoplasia UPJO at the same time. All clinical, perioperative, and postoperative information was collected.Results: There were four bilateral UPJO cases, two solitary kidney UPJO cases and three unilateral UPJO with contralateral renal hypoplasia cases included. One single surgeon performed RALP on all of the infants. The mean age of the infants was 1.62 ± 0.54 months. The mean operative time was 109.55 ± 10.47 min. The mean estimated blood loss was 19.29 ± 3.19 ml, and the mean length of hospital stay was 5.57 ± 0.73 days. According to the ultrasonography results, all patients had a significant recovery of renal function at 12 months after the operation.Conclusions: To maximize the protection of renal function, early RALP is a safe and feasible option for the treatment of severe UPJO in infants under 3 months.

Background The mortality risk of chronic interstitial lung disease (ILD) is currently assessed using the ILD-GAP score. The present study evaluates whether the addition of cardiopulmonary ultrasound parameters to the ILD-GAP score can further improve the predictive value of ILD-GAP. Methods Medical records from 91 patients with ILD hospitalized from June 2015 to March 2016 were retrospectively examined. The Lung ultrasound (LUS) score, right ventricular (RV) function, and mechanics were obtained from the cardiopulmonary ultrasound. The ILD-GAP score was calculated from demographic characteristics and pulmonary function parameters. Patients were followed up with until May 2020. The primary endpoint was all-cause death. Results After exclusions, 74 patients with ILD were included in the analysis. During the follow-up period, 36 patients with ILD survived (ILDs), and 38 patients died (ILDd). Compared to ILDs, the ILDd cases exhibited a higher number of B-lines, LUS score, and RV end-diastolic base dimension (RVD), but lower RV function. In multivariate analysis, the ILD-GAP score (hazard ratio, 2.88; 95% CI 1.38–5.99, P = 0.005), LUS score (hazard ratio 1.13; 95% CI 1.04–1.24, P = 0.006), and RVD (hazard ratio 1.09, 95% CI 1.03–1.16, P = 0.004) were significantly related to the risk of death. Adding the LUS score and RVD to the ILD-GAP score significantly improved the predictive value compared to the ILD-GAP score alone (C statistics 0.90 vs 0.76, P = 0.018). Conclusion We investigated the utility of a new prognostic model for ILD that includes both cardiopulmonary ultrasound parameters (LUS score and RVD) and the ILD-GAP score. This model better reflects the severity of pulmonary fibrosis and cardiac involvement, and has incremental predictive value over the ILD-GAP score alone.

It is a hybrid design spectrometer with MWIR zooming and spectral imaging. The system realizes the searching in large field of view and recognition in small field of view which can resolve the difficulty that the target and background of spectrometer are not easy to distinguish in a single field of view. It also decreases the difficulty of spectral analysis and data dimension reduction. The collimating light beam modulated by AOTF (acousto-optic tunable filter) provides a basis for the subsequent spectral analysis. The optical system realizes three times zoom from 160mm to 480mm. The simulation achieves the effect imaging result. Experiments show that the system has both imaging and spectral recognition capabilities.

Background: The objective of this study was to investigate the prognostic value of tumor size on cancer-specific mortality (CSM) and lymph node metastasis for patients with penile squamous cell carcinoma (PSCC).Method: The patients diagnosed with PSCC between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Restricted cubic spline functions were calculated to characterize the association between tumor size and the risk of CSM. The competing-risks model was used to evaluate the impact of tumor size on the cumulative incidence of CSM. The logistic regression analysis was performed to examine the association between tumor size and lymph node metastasis.Results: Totally, 1365 PSCC patients were analyzed, with 52.3% having tumors ≤30 mm, and 47.7% >30 mm. The restricted cubic splines showed that the risks of CSM increased as tumors enlarged. Following adjustment of competing events, the PSCC patients with tumors >30 mm were more likely to succumb to CSM in comparison with those with tumors ≤30 mm (hazard ratio [HR]=1.57, 95% confidence interval [CI]: 1.23-2.01, P30 mm was significantly associated with an increased risk of CSM relative to tumor size ≤30 mm among patients with T1 (HR=1.56, 95%CI: 1.03-2.37, P=0.036) and T3 (HR=2.51, 95%CI: 1.41-4.45, P=0.002) classifications. On logistic regression analysis, tumors >30 mm were significantly associated with lymph node metastasis (odds ratio [OR]=1.46, 95% CI: 1.03-2.07, P=0.034).Conclusion: Larger tumors (>30 mm) were significantly associated with higher risks of CSM and increased likelihood of lymph node metastasis for PSCC patients, which could be integrated into the development of a staging system for penile cancer.

CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy., CAR T therapy has some efficacy in the treatment of patients with refractory/relapsed B-cell acute lymphoblastic leukemia; however in some patients further relapse is encountered. Here, the authors conduct a Phase II clinical trial of a CD19 CAR T and demonstrate that patients with extramedullary disease are more likely to relapse than those without.

Congenital deficiency of tracheal rings is a rare tracheal malformation that can cause central airway obstruction. Herein we reported the clinical data of six patients with symptomatic congenital deficient tracheal rings. There were five cases, with isolated short-segment absent cartilage ring located on the distal trachea (three cases), cervical trachea (one case), and distal trachea combined with bilateral bronchi (one case). Among them, four (4/5) received surgical tracheal resection, three fully recovered, and one died of severe infection. Besides that, one patient, who could not be weaned off the mechanical ventilation, died after rejecting surgery. One case had episodes of recurrent dyspnea and extubation failure due to long-segment tracheomalacia after repair of esophageal atresia and tracheoesophageal fistula. For this patient, deficient cartilage rings were suspected and confirmed at the age of 26 months. Moreover, the clinical characteristics of 12 cases with congenital deficient tracheal cartilage rings reported in previous literature were reviewed. The different characteristics between short- and long-segment deficient cartilage rings were discussed.

BackgroundBronchial asthma (asthma) is a chronic respiratory inflammatory disease characterized by reversible airflow limitation and high airway reactivity. Current studies generally show that airway remodeling is the pathologic structural basis for the occurrence of reversible airflow restriction and airway hyper reactivity[1] [2].In the above process, airway smooth muscle cell (ASMC) hyperplasia and hypertrophy are considered to be the main mechanisms of airway remodeling[3]. Calcitriol can be combined with budesonide to more effectively inhibit airway inflammation and airway remodeling and play its role in the treatment of asthma[4, 5]. MethodsThe mouse airway smooth muscle cells were divided into blank group, TGF-β1 group, SIS3 group, budesonide group,calcitriol group and drug co-treatment group[6]. The IL-33 concentration in supernatant of each group was detected by ELISA method, and the expression of Smad3, pSmad3 and IL-33 protein in each group was detected by Western blotting method[7].ResultsELISA showed that the concentration of IL-33 in the supernatant of cell culture in budesonide group was lower than that in the calcitriolgroup, and the concentration of IL-33 in the drugco-treatment group was lower than that in any single drugtreatment group.The expression level of Smad3 protein, pSmad3 protein and IL-33 protein of western blot in the drug co-treatment group were significantly decreased[8, 9].ConclusionsCalcitriol combined with budesonide can effectively decrease the expression and secretion of IL-33 in mouseairway smooth muscle cells byactivatingTGF-β1/Smad3 signaling pathway [10].

Diabetic nephropathy is the leading cause of renal failure worldwide. Elevated inflammatory signaling has been shown to lead to deterioration of renal function in human and experimental diabetes. We recently developed a salviadione derivative (compound 15a) that prevented microbial lipopolysaccharide-induced inflammatory responses, which are largely driven by nuclear factor-κB (NF-κB). In the present study, we have tested the hypothesis that 15a will protect kidneys from diabetes-induced dysfunction by suppressing NF-κB activation and inflammatory signaling. Treatment of diabetic mice with 15a inhibited diabetes-induced renal fibrosis, NF-κB activation, and upregulation of proinflammatory cytokines. Histologically, kidney specimens from diabetic mice treated with 15a were indistinguishable from non-diabetic controls. We confirmed our findings in cultured renal tubular epithelial cells exposed to high levels of glucose. In these cultured cells, 15a pretreatment prevented high glucose-induced NF-κB activation and expression of inflammatory cytokines. These protective effects were also reflected in reduced levels of proteins involved in matrix expansion. Overall, our studies show that a salviadione derivative, 15a, is effective in suppressing diabetes-induced NF-κB activation and inflammatory signaling.

Background: Sepsis coagulopathy or disseminated intravascular coagulation (DIC) mainly due to progressive endothelial disruption and damage. The glycocalyx is expressed on the endothelial cell surface and contributes to anti-thrombogenicity, anti-inflammatory, and regulates vascular permeability. We aimed to evaluate the clinical utility of plasma glycocalyx components as biomarkers in predicting the onset of DIC in sepsis. Materials and methods: This was a prospective observational study of 45 patients with sepsis (June to December 2018). Demographic, clinical (Acute Physiology, Age, Chronic Health Evaluation II [APACHE II], Sequential Organ Failure Assessment [SOFA]), and laboratory data from medical records were analyzed. Endothelial glycocalyx components (syndecan-1, heparan sulfate, hyaluronan) were measured using an ELISA kit. Results: Among the 45 patients (23, sepsis; 22, septic shock), plasma syndecan-1, heparan sulfate, and hyaluronan levels were higher in those with septic shock and were positively correlated with disease severity as determined by the APACHE II and SOFA scores and lactate levels. Receiver operating characteristic curve analysis revealed high sensitivity and specificity of syndecan-1 for predicting septic shock. Further, these levels were compared between patients with or without the development of DIC. Plasma syndecan-1 and hyaluronan levels were significantly elevated in patients with DIC compared to those in patients without DIC and were strongly associated with activated partial thromboplastin time, prothrombin time, and platelet counts. Area under the curve values for predicting DIC based on syndecan-1 and hyaluronan levels measurements were 0.774 and 0.740, respectively. Conclusions: Increased plasma syndecan-1 and hyaluronan levels may be indicators of disease severity and useful predictors for DIC development in sepsis.

Neural tube defects (NTDs) are the most serious and common birth defects in the clinical setting. The Notch signaling pathway has been implicated in different processes of the embryonic neural stem cells (NSCs) during neural tube development. The aim of the present study was to investigate the expression pattern and function of Notch1 (N1) in all‑emtrans/emretinoic acid (atRA)‑induced NTDs and NSC differentiation. A mouse model of brain abnormality was established by administering 28 mg/kg atRA, and then brain development was examined using hematoxylin and eosin (Hamp;E) staining. The N1 expression pattern was detected in the brain of mice embryos via immunohistochemistry and western blotting. NSCs were extracted from the fetal brain of C57 BL/6 embryos at 18.5 days of pregnancy. N1, Nestin, neurofilament (NF), glial fibrillary acidic protein (GFAP) and galactocerebroside (GALC) were identified using immunohistochemistry. Moreover, N1, presenilin 1 (PS1), Nestin, NF, GFAP and GALC were detected via western blotting at different time points in the NSCs with control media or atRA media. Hamp;E staining identified that the embryonic brain treated with atRA was more developed compared with the control group. N1 was downregulated in the embryonic mouse brain between days 11 and 17 in the atRA‑treated group compared with the untreated group. The distribution of N1, Nestin, NF, GFAP and GALC was positively detected using immunofluorescence staining. Western blotting results demonstrated that there were significantly, synchronous decreased expression levels of N1 and PS1, but increased expression levels of NF, GFAP and GALC in NSCs treated with atRA compared with those observed in the controls (Plt;0.05). The results suggested that the N1 signaling pathway inhibited brain development and NSC differentiation. Collectively, it was found that atRA promoted mouse embryo brain development and the differentiation of NSCs by inhibiting the N1 pathway.

Chimeric antigen receptor (CAR) T cell therapy improves the remission rate of refractory/relapsed B-acute lymphoblastic leukemia (R/R B-ALL) patients, but the relapse rate remains high. Recent studies suggest patients who underwent post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation (post- HSCT) would achieve durable remission and better survival, but this remains controversial. To this end, we conducted a meta-analysis to assess the role of post-HSCT in R/R B-ALL. The Cochrane Library, Embase, and PubMed were used to identify relevant studies; the latest search update was on July 05, 2020. We used the Cochran Q test and I-squared statistics to test for heterogeneity among the studies analyzed. The fixed model and random model were used to combine results when appropriate. We performed all statistical analyses with Stata 12, and P < 0.05 was considered statistically significant. We included 18 studies with 758 patients in the meta-analysis. Our results indicated that post-HSCT was associated with lower relapse rate (RR: 0.40, 95% CI: 0.32-0.50, P = 0.000), better overall survival (HR: 0.37, 95% CI: 0.19-0.71, P = 0.003), better leukemia-free survival (HR: 0.20, 95% CI: 0.10-0.40, P = 0.000). However, post-HSCT did not influence OS in Caucasians, and CAR-T cells with CD28 co-stimulation factor bridged to HSCT did not influence OS. Post-HSCT decreased the relapse rate and improved the long-term survival of R/R B-ALL patients. R/R B-ALL patients would benefit from post-HSCT after CAR-T cell therapy.

Background: Aggressive care at the end of life (EOL) is a persistent issue for patients with stage IV nonsmall cell lung cancer (NSCLC). We evaluated the use of concurrent care (CC) with hospice care and cancer-directed treatment simultaneously within the Veteran's Health Administration (VHA) and aggressive care at the EOL. Objective: To determine whether VHA facility-level CC is associated with changes in aggressive care at the EOL. Design/Setting: Veterans with stage IV NSCLC who died between 2006 and 2012 and received lung cancer care within the VHA. Measurements: The primary outcome was aggressive care at EOL (i.e., hospital admissions, chemotherapy, and intensive care unit) within the last month of life. To compare aggressive care across VHA facilities, we used a random intercept multilevel logistic regression model to examine the association between facility-level CC within each study year (

Risk-stratification strategies are needed for ambulatory pediatric populations. The authors sought to develop age-specific risk scores that predict high health care costs among an urban population. A retrospective cohort study was performed of children ages 1-18 years who received care at Fair Haven Community Health Care (FHCHC), a community health center in New Haven, Connecticut. Cost was estimated from charges in the electronic health record (EHR), which is shared with the only hospital system in the city. Using multivariable logistic regression models, independent predictors of being in the top decile of total charges during the 2017 calendar year were identified, drawing from covariates collected from the EHR prior to 2017. Random forest modeling was used to verify the feature importance of significant covariates and model performance from 2017 cost data were compared to those using 2018 cost data. Regression models were used to construct age-specific nomograms to predict cost. Among 8960 children who received care at FHCHC in the 18 months prior to 2017, covariate frequencies clustered in age groups 1-5 years, 6-11 years, and 12-18 years, so 3 age-specific models were constructed. Prior utilization variables predicted future costs, as did younger children who received specialty care and older children with behavioral health diagnoses. Final models for each age group had C statistics ≥0.68 using both 2017 and 2018 cost data. Prediction models can draw from elements accessible in the EHR to predict cost of ambulatory pediatric patients. Strategies to impact utilization among high-risk children are needed.

Hepatocellular carcinoma (HCC) is a malignant tumour associated with a high mortality rate and poor prognosis worldwide. Uridine diphosphate-glucose pyrophosphorylase 2 (UGP2), a key enzyme in glycogen biosynthesis, has been reported to be associated with the occurrence and development of various cancer types. However, its diagnostic value and prognostic value in HCC remain unclear. The present study observed that UGP2 expression was significantly downregulated at both the mRNA and protein levels in HCC tissues. Receiver operating characteristic (ROC) curve analysis revealed that UGP2 may be an indicator for the diagnosis of HCC. In addition, Kaplan-Meier and Cox regression multivariate analyses indicated that UGP2 is an independent prognostic factor of overall survival (OS) in patients with HCC. Furthermore, gene set enrichment analysis (GSEA) suggested that gene sets negatively correlated with the survival of HCC patients were enriched in the group with low UGP2 expression levels. More importantly, a significant correlation was identified between low UGP2 expression and fatty acid metabolism. In summary, the present study demonstrates that UGP2 may contribute to the progression of HCC, indicating a potential therapeutic target for HCC patients.