Associations between R.E.N.A.L. nephrometry score and survival outcomes in renal tumours.

OBJECTIVE: The radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score could be used to predict surgical outcomes and renal tumour aggressiveness. We aimed to analyse its associations with survival outcomes. METHODS: We included 1368 patients with sporadic, unilateral and non-metastatic renal tumours who received curative nephrectomy in Zhongshan Hospital from January 2009 to September 2019. Radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores were assigned by three urologists based on preoperative CT/MRI scans. Correlations between parameters or sum of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores, overall survival and recurrence-free survival were analysed by Kaplan-Meier analyses and the multivariate Cox regression model. We further compared survival outcomes between patients who received partial nephrectomy and patients who received radical nephrectomy. RESULTS: We observed statistically significant associations between all components of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores and oncologic outcomes, including R (radius) (overall survival, P < 0.001; recurrence-free survival , P < 0.001), E (exophytic/endophytic) (overall survival, P = 0.003; recurrence-free survival, P < 0.001), N (nearness) (overall survival, P = 0.063; recurrence-free survival, P < 0.001), A (anterior/posterior) (overall survival, P < 0.001; recurrence-free survival, P = 0.005), L (location) (overall survival, P = 0.008; recurrence-free survival, P < 0.001) and suffix 'h' (overall survival, P = 0.237; recurrence-free survival, P = 0.034). Kaplan-Meier curves of overall survival and recurrence-free survival rates were significantly different when stratified by radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score complexity group (overall survival, P < 0.001; recurrence-free survival, P < 0.001). After adjusting for tumour stage and grade, radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score as continuous variables was an adverse independent risk factor for survival outcomes [P = 0.027, hazard ratio (95% confidence interval) = 1.151 (1.016-1.303)] and recurrence-free survival [P < 0.001, hazard ratio (95% confidence interval) = 1.299 (1.125-1.501)]. For tumours with radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores of 4 and 5, partial nephrectomy showed a survival benefit than radical nephrectomy. CONCLUSION: Both components and complexity groups of the radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score are associated with survival outcomes in renal tumour patients.

Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with HR+, HER2+ advanced breast cancer: plain language summary of the monarcHER study.

WHAT IS THIS SUMMARY ABOUT?: This article summarizes the results of a study called monarcHER. The study included participants with a certain type of aggressive breast cancer called HR+, HER2+ advanced breast cancer (ABC) that had their disease worsen or return after multiple previous therapies. This summary intends to help you understand the impact of a non-chemotherapy treatment called abemaciclib in people with HR+, HER2+ ABC. When the study was planned, HER2-targeted therapy (ie trastuzumab) was standard treatment and was typically combined with chemotherapy and endocrine therapy (ie fulvestrant). However drug resistance can develop when HER2+ targeted therapy is used for a long time, making it less effective and allowing cancer to grow or spread to other parts of the body. When this happens, few chemotherapy-free options are available. Because of the chemotherapy side effects, this is not desirable. There is an urgent need to develop new, effective, safe, and tolerable treatment options for patients with HR+, HER2+ ABC. The monarcHER study compared the effects of abemaciclib plus trastuzumab with or without fulvestrant compared to the standard of care treatment. WHAT WERE THE RESULTS?: Participants were randomly assigned to 1 of 3 groups: Group A (abemaciclib, trastuzumab and fulvestrant), Group B (abemaciclib and trastuzumab), or Group C (trastuzumab and standard of care chemotherapy). The study compared the length of time patients took study treatments without worsening or dying from their breast cancer. This is called the progression free survival (PFS). Participants in Group A had a longer median PFS than those in groups B and C (8.3 months, 5.7 months and 5.7 months respectively). There was no notable difference in PFS between participants in Groups B and C. Additionally, the study looked at the side effects with each treatment group. The most common side effect which is considered severe or lifethreatening was neutropenia, defined as decreased white blood cell levels. Neutropenia may lead to an increased risk of getting infections. However, the percentage of patients experiencing neutropenia was similar in all groups A, B and C (27%, 22% and 26%, respectively). Patients in groups A (79%) and B (78%) who received abemaciclib experienced similar rates of diarrhea. WHAT DO THE RESULTS MEAN?: The data from the monarcHER study suggest that the combination of abemaciclib, trastuzumab, and fulvestrant may offer a chemotherapy-free option for patients with HR+, HER2+ ABC who have experienced worsening of disease despite multiple prior therapies.

Clinical experience using peripheral blood parameters to analyse the mutation type of thalassemia carriers in pregnant women.

Thalassaemia is a typically monogenic disease caused by mutations or deletions in the globin gene and has a high prevalence in southern China. Prenatal screening for thalassaemia can be effective in reducing the incidence of thalassaemia. Haematologic parameters of pregnant thalassaemia carriers are diverse and potentially valuable for identifying different types of genotypes. By comparing and evaluating haematological parameters, formulas in the literature, we tried to reveal differences between pregnant women carrying different types of thalassaemia genes. The Mentzer formula (MCV/RBC) showed a strong ability to differentiate thalassaemia genotypes in pregnant women. In addition, combined with haemoglobin electrophoresis HbA2 can further distinguish the -α/αα, αTα/αα, -/αα, ß+/N and ß0/N groups. HbA2 divides them into two groups. Based on the Mentzer formula, we can further decide which type of thalassaemia to screen (α/ß and the subgroups) for genotyping. Therefore, this simpler and more cost-effective workflow has great potential for application in screening pregnant women for thalassaemia carriers.Impact StatementWhat is already known on this subject? Currently, it is known that thalassaemia gene carriers have abnormal blood indicators. Many findings describe their important values in distinguishing thalassaemia and other blood diseases. They combined different metrics as an algorithm to distinguish thalassaemia and iron deficiency anaemia. Prenatal screening is an effective method to reduce the incidence of thalassaemia. The current main method is PCR. Due to technical and financial constraints, many backward places cannot use this technology. The necessity for prenatal screening for thalassaemia has been overlooked.What the results of this study add? Among these algorithms, Mentzer formula revealed differences in haematological parameters during pregnancy between normal individuals and thalassaemia carriers. Combining the HbA2, thalassaemia carriers can be distinguished from normal individuals, including -α/αα, αTα/αα, -/αα, ß0/N and ß+/N.What are the implications of these findings for clinical practice and/or further research? We provide another tool for these hospitals that donot have Hb electrophoresis test and PCR. Then the clinical doctor can get some evidence and suggest women go to another big hospital for essential tests. It is an excellent suggestion. In the future, we will collect more specific gene types and further investigate their potential relationship using these formulas.

[Randomized Controlled Study on the Improvement of Community Residents' Mental Health Literacy Through Online Popular Science Program].

Objective: To explore the effects of online mental health promotion intervention consisting of popular science articles and short videos on the level of mental health literacy (MHL), the MHL competency rate, and depression and anxiety levels of local residents. Methods: Local residents in Shanghai were recruited for the study and assigned to a control group ( n=53) and a study group ( n=53) with a random number table. The study group participated in a 12-session mental health promotion intervention program that was carried out over the course of 4 weeks, while the control group did not receive any intervention. The subjects were assessed for their MHL, depression and anxiety by questionnaire surveys at the baseline (T1), after intervention (T2), and three months after intervention (T3). Results: At T2, there was significant difference in the rate of MHL competency between the study group (43.40%) and the control group (18.87%) ( P=0.006). There was no significant difference between the two groups at T1 ( P=0.787) or T3 ( P=0.840). The results of repeated measures analysis of variance of the total score of the MHL Questionnaire showed that the interaction effect was statistically significant ( F=9.708, P<0.001), the simple effect of grouping was statistically significant at T2 ( F=10.935, P=0.001), and the total score of MHL of the study group (134.321±20.123) was significantly higher than that of the control group (123.811±20.224) for the corresponding point of time. The simple effect of time in the study group was statistically significant ( F=23.233, P<0.001). The subjects in the study group scored significantly higher at T2 and T3 than they did at T1, or the baseline ( P<0.001). There was no significant difference between the T2 and the T3 scores ( P=0.847). Conclusion: The 12-session online mental health promotion intervention can effectively improve the subjects' MHL level and the rate of MHL competency immediately after the invention was completed, and the effect endures 3 months after intervention.

An open label, randomized phase 2 trial assessing the impact of food on the tolerability of abemaciclib in patients with advanced breast cancer.

PURPOSE: Abemaciclib, a CDK4 & 6 inhibitor, is indicated for advanced breast cancer treatment. Diarrhea is a frequently associated adverse event of abemaciclib. The study objective was to investigate if food intake impacts local gastrointestinal toxicity. METHODS: This Phase 2 study (I3Y-MC-JPCP, NCT03703466) randomized 72 patients 1:1:1 to receive abemaciclib 200 mg monotherapy twice daily (1) with a meal, (2) in a modified fasting state or (3) without regard to food. Primary endpoints included: incidence of investigator assessed severe (≥ Grade 3), prolonged (> 7 days) Grade 2 diarrhea, treatment discontinuation, dose modifications, and loperamide utilization during the first 3 cycles of treatment. Patient outcomes were captured via a daily electronic diary. Pharmacokinetics (PK) are reported. RESULTS: Incidence of investigator assessed severe diarrhea (Grade ≥ 3) was 1.4% (1 patient in Arm 1). Median duration of Grade 3 diarrhea was 1 day by both investigator assessment (1 patient in Arm 1) and patient-reported assessment (1 patient each in Arms 1 and 3). Median duration of investigator-assessed Grade 2 diarrhea was 2 days overall. No patient discontinued treatment due to diarrhea. Nine patients (12.7%) had a dose reduction, and 7 patients (9.9%) had a dose omission due to diarrhea. Ninety-four percent of patients used loperamide at least once. Abemaciclib PK was comparable across the 3 arms. CONCLUSION: The results suggest that diarrhea incidence associated with abemaciclib was unrelated to timing of food intake, was predominantly low grade, of short duration and well managed with loperamide and dose modifications.

nextMONARCH Phase 2 randomized clinical trial: overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with endocrine-refractory HR + , HER2- metastatic breast cancer.

PURPOSE: Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). We present the preplanned 24-month final overall survival (OS) results, alongside updated progression-free survival (PFS), and objective response rate (ORR) results. METHODS: nextMONARCH is an open-label, controlled, randomized, Phase 2 study of abemaciclib alone or in combination with tamoxifen in women with endocrine-refractory HR + , HER2- MBC previously treated with chemotherapy. Patients were randomized 1:1:1 to: abemaciclib 150 mg and tamoxifen 20 mg (A + T), abemaciclib 150 mg (A-150), or abemaciclib 200 mg and prophylactic loperamide (A-200). OS was the main prespecified secondary endpoint. PFS, ORR, and safety at 24 months were compared to previously reported primary analysis results. RESULTS: Of the 234 patients enrolled, 12 were receiving study treatment at data cutoff (28Jun2019). Median follow-up was 27.2 months. Median OS was 24.2 months in the A + T arm, 20.8 months in A-150, and 17.0 months in A-200 (A + T versus A-200: HR 0.62; 95%CI [0.40, 0.97], P = 0.03 and A-150 versus A-200: HR 0.96; 95%CI [0.64, 1.44], P = 0.83). PFS and ORR results at 24 months were consistent with the primary analysis. The safety profile corresponded with previous reports. CONCLUSION: The addition of tamoxifen to abemaciclib demonstrated greater OS benefit than monotherapy. This study confirmed the single-agent activity of abemaciclib in heavily pretreated women with endocrine-refractory HR + , HER2- MBC, as well as the previously reported primary PFS and ORR results, with no new safety signals observed. Trial Registration ClinicalTrials.gov Identifier: NCT02747004.

Diagnostic and Prognostic Performance of Serum Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptor 2, and Osteopontin for Gastrointestinal Cancers.

BACKGROUND: Biomarkers for early diagnosis and follow-up of cancers are still underutilized in clinical management. Thus, seeking new biomarkers with better sensitivity and specificity is still a challenge. VEGF, VEGFR2, and OPN are newly emerging biomarkers with clinical potential. METHODS: ELISA was used to analyze serum VEGF, VEGFR2, and OPN from 75 gastrointestinal cancer patients and 75 control subjects. The correlation of pre-operative serum VEGF, VEGFR2, and OPN levels with CEA, Ki-67 as well as clinical features (age, gender, tumor size, TNM stage, tumor stage, lymph node involvement, metastasis, and histological grading) in these patients. RESULTS: The pre-operative and post-operative serum VEGF and VEGFR2 levels and the post-operative OPN level in patients were significantly higher than in controls (p = 0.000, for all mentioned). The post-operative VEGF and OPN levels were significantly higher than that of pre-operative (p = 0.000 and 0.007, respectively). There was no correlation between pre-operative serum VEGF, VEGFR2, and OPN levels and serum CEA concentration. The pre-operative serum VEGF level was significantly correlated with the tumor Ki-67 scores; however, there was no correlation between serum VEGFR2 and OPN and Ki-67 scores. Univariate logistic regression analysis revealed that serum VEGF level was significantly higher in patients with advanced TNM (III - IV) stage and with lymph node involvement than in patients with low TNM stage (I - II) and with no lymph node involvement. High OPN level was correlated with metastasis. Multivariate logistic regression analysis results showed that serum VEGF and VEGFR2 were the two most important factors for the diagnosis of gastrointestinal cancers in this study (p = 0.000, for both). Combinatorial analysis of the biomarkers improved the performance of the assays. CONCLUSIONS: Serum VEGF and VEGFR2 are potential biomarkers for the diagnosis and prognosis evaluation of gastrointestinal cancers, while serum OPN is a potential biomarker for the prognostication of gastrointestinal cancers.

Alteration of Serum 25(OH) Vitamin D, Vitamin D Binding Protein, and C-reactive Protein Levels in Acute Leukemia Patients.

BACKGROUND: Acute leukemia is a common hematologic malignancy with poorly differentiated leukocytes. Alteration of circulating vitamin D (VD) and its carrier vitamin D binding protein (VDBP) have been reported in certain types of cancers and may play a role in the course of the disease. Understanding of the status of serum VD and VDBP, as well as the acute phase protein C-reactive protein (CRP) levels in pre- and post-treatment of acute leukemia patients, may be helpful in the management of acute leukemia. METHODS: Enzyme linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and immunofluorescent assay were used to analyze the 25(OH) vitamin D (25(OH)D), VDBP, and CRP in the serum of a cohort of leukemia patients. RESULTS: Serum 25(OH)D levels in patients (pre- and post-treatment) were significantly lower than in control subjects. There was no significant difference in 25(OH)D levels between pre- and post-treatment. Serum VDBP level was raised in both pre- and post-treatment of acute leukemia patients, with that of pre-treatment being higher. The average serum VDBP was reduced in post-treatment; however, no significant difference was found. Elevated serum CRP levels in both pre- and post-treatment patient groups have been observed but were reduced significantly after treatment. Results also revealed that serum VDBP levels in acute myeloid leukemia patients were significantly higher than in acute lymphoid leukemia patients, while 25(OH)D levels in acute myeloid leukemia were significantly lower than in acute lymphoid leukemia. No significant difference between the serum CRP levels of acute myeloid leukemia and acute lymphoid leukemia was observed. CONCLUSIONS: Serum 25(OH)D, VDBP, and CRP may be used together and could be potential indicators of the disease course of acute leukemia and assist in its management which merits further investigation.

A Novel Nociceptin Receptor Antagonist LY2940094 Inhibits Excessive Feeding Behavior in Rodents: A Possible Mechanism for the Treatment of Binge Eating Disorder.

Nociceptin/orphanin FQ (N/OFQ), a 17 amino acid peptide, is the endogenous ligand of the ORL1/nociceptin-opioid-peptide (NOP) receptor. N/OFQ appears to regulate a variety of physiologic functions including stimulating feeding behavior. Recently, a new class of thienospiro-piperidine-based NOP antagonists was described. One of these molecules, LY2940094 has been identified as a potent and selective NOP antagonist that exhibited activity in the central nervous system. Herein, we examined the effects of LY2940094 on feeding in a variety of behavioral models. Fasting-induced feeding was inhibited by LY2940094 in mice, an effect that was absent in NOP receptor knockout mice. Moreover, NOP receptor knockout mice exhibited a baseline phenotype of reduced fasting-induced feeding, relative to wild-type littermate controls. In lean rats, LY2940094 inhibited the overconsumption of a palatable high-energy diet, reducing caloric intake to control chow levels. In dietary-induced obese rats, LY2940094 inhibited feeding and body weight regain induced by a 30% daily caloric restriction. Last, in dietary-induced obese mice, LY2940094 decreased 24-hour intake of a high-energy diet made freely available. These are the first data demonstrating that a systemically administered NOP receptor antagonist can reduce feeding behavior and body weight in rodents. Moreover, the hypophagic effect of LY2940094 is NOP receptor dependent and not due to off-target or aversive effects. Thus, LY2940094 may be useful in treating disorders of appetitive behavior such as binge eating disorder, food choice, and overeating, which lead to obesity and its associated medical complications and morbidity.

Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients.

PURPOSE: The monarcHER trial has shown that abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, combined with fulvestrant and trastuzumab, improves progression-free survival (PFS) in hormone receptor-positive (HR+), HER2-positive (HER2+) advanced breast cancer (ABC) compared with standard-of-care (SOC) chemotherapy combined with trastuzumab. We report the final overall survival (OS) analysis, updated safety and efficacy data, and exploratory biomarker results from monarcHER. PATIENTS AND METHODS: monarcHER (NCT02675231), a randomized, multicenter, open-label, phase II trial, enrolled 237 patients across Arm A (abemaciclib, trastuzumab, fulvestrant), Arm B (abemaciclib, trastuzumab), and Arm C (SOC chemotherapy, trastuzumab). Following the statistical plan, OS and PFS were estimated in all arms. RNA sequencing (RNA-seq) was performed on archival tissue. RESULTS: Median OS was 31.1 months in Arm A, 29.2 months in Arm B, and 20.7 months in Arm C [A vs. C: HR, 0.71; 95% confidence interval (CI), 0.48-1.05; nominal two-sided P value 0.086; B vs. C: HR 0.83 (95% CI, 0.57-1.23); nominal two-sided P value 0.365]. Updated PFS and safety findings were consistent with previous results. The most frequently reported treatment-emergent adverse events included diarrhea, fatigue, nausea, neutrophil count decrease, and anemia. In exploratory RNA-seq analyses, Luminal subtypes were associated with longer PFS [8.6 vs. 5.4 months (HR, 0.54; 95% CI, 0.38-0.79)] and OS [31.7 vs. 19.7 months (HR, 0.68; 95% CI, 0.46-1.00)] compared with non-Luminal. CONCLUSIONS: In this phase II trial, abemaciclib + trastuzumab ± fulvestrant numerically improved median OS in women with HR+, HER2+ ABC compared with SOC chemotherapy + trastuzumab.

Genetic ablation of myelin protein zero-like 3 in mice increases energy expenditure, improves glycemic control, and reduces hepatic lipid synthesis.

Obesity continues to be a global health problem, and thus it is imperative that new pathways regulating energy balance be identified. Recently, it was reported: (Hayashi K, Cao T, Passmore H, Jourdan-Le Saux C, Fogelgren B, Khan S, Hornstra I, Kim Y, Hayashi M, Csiszar K. J Invest Dermatol 123: 864-871, 2004) that mice carrying a missense mutation in myelin protein zero-like 3 (Mpzl3rc) have reduced body weight. To determine how Mpzl3 controls energy balance in vivo, we generated mice deficient in myelin protein zero-like 3 (Mpzl3-KO). Interestingly, KO mice were hyperphagic yet had reduced body weight and fat mass. Moreover, KO mice were highly resistant to body weight and fat mass gain after exposure to a high-fat, energy-dense diet. These effects on body weight and adiposity were driven, in part, by a pronounced increase in whole body energy expenditure levels in KO mice. KO mice also had reduced blood glucose levels during an intraperitoneal glucose challenge and significant reductions in circulating insulin levels suggesting an increase in insulin sensitivity. In addition, there was an overall increase in oxidative capacity and contractile force in skeletal muscle isolated from KO mice. Hepatic triglyceride levels were reduced by 92% in livers of KO mice, in part due to a reduction in de novo lipid synthesis. Interestingly, Mpzl3 mRNA expression in liver was increased in diet-induced obese mice. Moreover, KO mice exhibited an increase in insulin-stimulated Akt signaling in the liver, further demonstrating that Mpzl3 can regulate insulin sensitivity in this tissue. We have determined that Mpzl3 has a novel physiological role in controlling body weight regulation, energy expenditure, glycemic control, and hepatic triglyceride synthesis in mice.

[Effect of Deep Vertical Rotary Tillage on Soil Bacterial Community Diversity and Microbial Network Structure in Cultivated Land].

The aim of this study was to understand the effect of deep vertical rotary tillage on the diversity and structural distribution of a soil bacterial community in cultivated land, as well as the interactions between microbial ecological molecular network and species. In this study, the cultivated soil under different tillage methods in the Yellow River diversion irrigation area in Ningxia was selected as the research object, and two treatments were set up, namely, deep vertical rotary tillage (DVRT) and conventional tillage (CT). Then, Illumina MiSeq technology was used to analyze the molecular ecological network of soil bacterial community under different tillage methods in the Ningxia Yellow River irrigation area. The results showed that DVRT significantly increased the contents of total organic carbon (TOC), total nitrogen (TN), alkali-hydrolyzed nitrogen (AN), total phosphorus (TP), available phosphorus (AP), and total potassium (TK) in the 0-20 cm soil layer compared with those in the CT treatment. Compared with those in the CT treatment, DVRT significantly increased the contents of TOC, TN, TP, AP, TK, and available potassium (AK) in the 20-40 cm soil layer. DVRT treatment significantly increased water content (WC) by 8.13%-13.30% and decreased pH and electrical conductivity (EC) by 4.51%-5.85% and 12.5%-13.33%, respectively. In different growth stages and soil layers of maize, the Shannon and Ace indices were increased in the DVRT treatments. The dominant bacterial phyla were:Actinobacteria, Proteobacteria, Chloroflexi, Acidobacteriota, and Gemmatimonadota. The results of bacterial community ß diversity showed that DVRT and CT had significant differences in bacterial community structure. The redundancy analysis and Partial Mantel test results showed that pH, EC, and TP were the key environmental factors affecting the structural diversity of bacterial communities. Molecular ecological network analysis revealed that DVRT treatment microbial networks consisted of more functionally related microbial modules, and the topological roles of key microorganisms were different from those in the CT treatment. In conclusion, DVRT can enhance soil nutrients and WC in different soil layers, reduce pH and EC, improve soil bacterial community diversity and microbial network structure, and also enhance the potential ecosystem functions in cultivated soil.

Designing a Compact Filtering Quasi-Yagi Antenna with Multiple Radiation Nulls Using Embedded Resistor-Loaded Arms.

In this paper, a compact quasi-Yagi antenna with embedded resistor-loaded arms is proposed to obtain a filtering response with four radiation nulls. The embedded resistor-loaded arms achieve two additional radiation nulls caused by reverse currents and absorb the unwanted out-of-band resonant points brought by themselves. The director close to the driver provides a resonant point and a radiation null caused by opposite currents between the driver and the director. Compared with other filtering quasi-Yagi antennas, the proposed one can achieve a filtering response with a compact size along the endfire direction. For demonstration, a balun-integrated prototype covering the 5G band N78 (3.3-3.8 GHz) is designed with the size along the endfire direction (without ground) of 0.13 λ0 (λ0 is the wavelength in the free space at center frequency), and the measured results show a 10 dB impedance-matching bandwidth of 22.9% (3.21-4.04 GHz), four radiation nulls, and a peak gain of 4.73 dBi.

Blood biomarkers in the application of diagnosis and prediction of overall survival for 1089 patients with nasopharyngeal carcinoma.

Previous studies have indicated that some blood metrics play a crucial role in the diagnostic and prognostic values of various solid tumours. However, their comprehensive and unbiased comparison for nasopharyngeal carcinoma (NPC) has not been performed. Twenty blood metrics evaluated in tumours or noncancerous diseases were selected. We selected 1089 patients with NPC and analyzed the relationship between these metrics, clinical characteristics, and overall survival (OS). The albumin and prognostic nutritional index (PNI) exhibited a high area under the curve (AUC) value (> 0.7) together with high "sensitivity (Sen) + specificity (Spe) (> 1.5)" or Youden index (> 0.5) when compared to healthy populations. In comparing NPC and nasal polyps, 9 of 20 blood metrics showed a high AUC value (> 0.7). However, only the PNI and international normalised ratio show a sufficiently high Sen + Spe or Youden Index. None of them could distinguish the status of the TNM classification well. Only the lymphocyte-to-monocyte ratio (LMR) could predict the OS of patients with NPC (cut-off, 4.91; p = 0.0069). Blood metrics as non-invasive biomarkers are valuable tools for clinical management. Among these indicators, PNI is the most ideal indicator to distinguish NPC from healthy and nasal polyps. The LMR has good prognostic value.

Emerging strategies of engineering retinal organoids and organoid-on-a-chip in modeling intraocular drug delivery: Current progress and future perspectives.

Retinal diseases are a rising concern as major causes of blindness in an aging society; therapeutic options are limited, and the precise pathogenesis of these diseases remains largely unknown. Intraocular drug delivery and nanomedicines offering targeted, sustained, and controllable delivery are the most challenging and popular topics in ocular drug development and toxicological evaluation. Retinal organoids (ROs) and organoid-on-a-chip (ROoC) are both emerging as promising in-vitro models to faithfully recapitulate human eyes for retinal research in the replacement of experimental animals and primary cells. In this study, we review the generation and application of ROs resembling the human retina in cell subtypes and laminated structures and introduce the emerging engineered ROoC as a technological opportunity to address critical issues. On-chip vascularization, perfusion, and close inter-tissue interactions recreate physiological environments in vitro, whilst integrating with biosensors facilitates real-time analysis and monitoring during organogenesis of the retina representing engineering efforts in ROoC models. We also emphasize that ROs and ROoCs hold the potential for applications in modeling intraocular drug delivery in vitro and developing next-generation retinal drug delivery strategies.

cGAS inhibition alleviates Alu RNA-induced immune responses and cytotoxicity in retinal pigmented epithelium.

BACKGROUND: The degeneration of retinal pigmented epithelium (RPE) cells results in severe diseases, such as age-related macular degeneration (AMD) that causes blindness in millions of individuals. RESULTS: We report that targeting GMP-AMP (cGAMP) synthase (cGAS) alleviates Alu RNA-induced immune responses and cytotoxicity in RPE. We find that the deletion of cGAS in RPE inhibits the Alu RNA-stimulated interferon production. cGAS deficiency also protects RPE from cell death triggered by Alu RNA. Importantly, two natural chemicals, epigallocatechin gallate (EGCG) and resveratrol (RSVL), are effective in suppressing the immunogenic and cytotoxic effect of Alu RNA in RPE. CONCLUSIONS: Our findings further demonstrate the crucial role of cGAS in the Alu RNA-induced RPE damage and present EGCG and RSVL as potential therapies for AMD and other RPE degeneration-related conditions.

Water-soluble non-starch polysaccharides of wild-simulated Dendrobium catenatum Lindley plantings on rocks and bark of pear trees.

The total water-soluble polysaccharide (TP) of Dendrobium catenatum is composed of starch and active non-starch polysaccharides (NSPs) with glucomannan as the main structural type. Although the TP content has been used as a quality assessment indicator for many years, the NSPs content in samples from different environments and growth seasons have not been reported. In this study, we found that NSPs had stronger antioxidant activity than TP. The NSPs content was higher in wild-simulated environments including rocks and trees compared to plantings grown in greenhouse. The culture mode and growth period affected the ratio of NSPs and starch. Facility cultivation provided optimal growth conditions but produced more starch, whereas wild-simulated cultivation resulted in a higher ratio of NSPs, particularly in September. Therefore, cultivation by lithophytation and epiphytation may be preferable to facility plantings, which is expected to be enormously useful for the current production and quality control of D. catenatum.

Urinary Excretion of Cyanuric Acid in Association with Urolithiasis: A Matched Case-Control Study in Shanghai Adults.

Melamine (MEL) has raised human concern since the 2008 milk scandal. Co-exposure to MEL and one of its analogues, cyanuric acid (CYA), has been reported to have a synergistic effect on promoting urolithiasis. However, few epidemiological studies have reported urolithiasis in association with exposure to CYA based on our knowledge. We therefore conducted a case-control study to investigate whether cases of urolithiasis had higher excretion of urinary CYA than the controls. Spot urine samples from 70 adult cases and first-morning urine samples from 70 controls (matched by age and sex) were collected for the measurement of MEL, CYA, and other two analogues in urine. The case group also had 2.81-fold higher concentration of urinary CYA than the control group (34.87 versus 12.43 ng/mL, p-value < 0.001). Multivariate conditional logistic regression models adjusting potential confounders of personal characteristics identified the risk factor of urinary CYA as a continuous variable with odds ratio (OR) (95% confidence interval, 95%CI) of 1.11 (1.02−1.21) (p-value = 0.021) and having meals at restaurants with OR of 5.71 (1.01−32.31) (p-value = 0.049). Compared to the participants having the lowest quartile of CYA concentration in urine, participants at the second, third, and fourth quartile groups had ORs of 13.94, 83.69, and 118.65 with p-values of 0.004, <0.001, and <0.001, respectively. The high excretion of urinary CYA in urolithiasis cases might be the sign of stones in patients consisting of CYA, then proving the attribution of CYA exposure in the etiology of urolithiasis. These findings are important since CYA is a degraded by-product of chlorinated isocyanuric acid disinfectants, which are widely used in daily life not only in swimming pool water but also in other scenarios, such as serving as anti-pandemic disinfectants. Risk assessment of CYA serving as a by-product of disinfectants needs to be conducted in future studies.

Abemaciclib in combination with pembrolizumab for HR+, HER2- metastatic breast cancer: Phase 1b study.

This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) without prior CDK4 and 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) and pretreated (cohort 2). Patients received abemaciclib plus pembrolizumab with (cohort 1) or without (cohort 2) anastrozole over 21-day cycles. The primary objective was safety, and secondary objectives included efficacy and pharmacokinetics (PK). Cohort 1/2 enrolled 26/28 patients, respectively. Neutropenia (30.8/28.6%), AST increase (34.6/17.9%), ALT increase (42.3/10.7%), and diarrhea (3.8/10.7%) were the most frequent grade ≥3 adverse events in cohort 1/2, respectively. A total of two deaths occurred, which investigators attributed to treatment-related adverse events (AEs), both in cohort 1. Higher rates of all grade and grade ≥3 interstitial lung disease (ILD)/pneumonitis were observed compared to previously reported with abemaciclib and pembrolizumab monotherapy. The PK profiles were consistent between cohorts and with previous monotherapy studies. In cohorts 1/2, the overall response rate and disease control rate were 23.1/28.6% and 84.6/82.1%, respectively. Median progression-free survival and overall survivals were 8.9 (95% CI: 3.9-11.1) and 26.3 months (95% CI: 20.0-31.0) for cohort 2; cohort 1 data are immature. Abemaciclib plus pembrolizumab demonstrated antitumor activity, but high rates of ILD/pneumonitis and severe transaminase elevations occurred with/without anastrozole compared to the previous reporting. Benefit/risk analysis does not support further evaluation of this combination in the treatment of HR+, HER2- MBC.