Risk stratification models incorporating oxidative stress factors to predict survival and recurrence in patients with gastric cancer after radical gastrectomy: A real-world multicenter study.

BACKGROUND: Oxidative stress significantly influences the development and progression of gastric cancer (GC). It remains unreported whether incorporating oxidative stress factors into nomograms can improve the predictive accuracy for survival and recurrence risk in GC patients. METHODS: 3498 GC patients who underwent radical gastrectomy between 2009 and 2017 were enrolled and randomly divided into training cohort (TC) and internal validation cohort (IVC). Cox regression analysis model was used to evaluate six preoperative oxidative stress indicators to formulate the Systemic oxidative stress Score (SOSS). Two nomograms based on SOSS was constructed by multivariate Cox regression and validated using 322 patients from another two hospitals. RESULTS: A total of 3820 patients were included. The SOSS, composed of three preoperative indicators-fibrinogen, albumin, and cholesterol-was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS). The two nomograms based on SOSS showed a significantly higher AUC than the pTNM stage (OS: 0.830 vs. 0.778, DFS: 0.824 vs. 0.775, all P < 0.001) and were validated in the IVC and EVC (all P < 0.001). The local recurrence rate, peritoneal recurrence rate, distant recurrence rate and multiple recurrence rate in high-risk group were significantly higher than those in low-risk group (P < 0.05). CONCLUSIONS: The two novel nomograms based on SOSS which was a combination score of three preoperative blood indicators, demonstrated outstanding predictive abilities for both survival and recurrence in GC patients with different risk groups, which may potentially improve survival through perioperatively active intervention strategies and individualized postoperatively close surveillance.

Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma.

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.

CDK4/6 Inhibitor Efficacy in ESR1-Mutant Metastatic Breast Cancer.

BACKGROUND: In estrogen receptor-positive metastatic breast cancer, ESR1 mutations (ESR1m) are a common mechanism of acquired resistance to aromatase inhibitors (ArIh). However, the impact ESR1 alterations have on CDK4/6 inhibitor (CDK4/6i) sensitivity has not been established. Analyses of CDK4/6i trials suggest that the endocrine therapy partner and specific ESR1 allele may affect susceptibility. We analyzed a real-world data set to investigate CDK4/6i efficacy in ESR1m metastatic breast cancer and associated clinical factors. METHODS: ESR1m were identified by analysis of circulating-tumor deoxyribonucleic acid. The GuardantINFORM database contains genomic information from tumors linked with claims data. Patients who started a CDK4/6i within 30 days of sequencing were categorized as having ESR1m or non-ESR1-mutant (non-ESR1m) breast cancer. Data were analyzed to determine the real-world time-to-next-treatment, defined as the start of a breast cancer treatment to initiation of the subsequent treatment. RESULTS: One hundred forty-five patients with ESR1m and 612 with non-ESR1m metastatic breast cancer were analyzed. ESR1m and non-ESR1m tumors had similar real-world time-to-next-treatment on CDK4/6i regimens (hazard ratio, 1.02; 95% confidence interval, 0.82 to 1.23). Duration on therapy in the first-line and second-line plus treatment settings were comparable regardless of ESR1 status. We stratified treatment duration by concurrent endocrine therapy, and patients with ESR1m had worse outcomes on ArIh but comparable real-world time-to-next-treatment on fulvestrant. CONCLUSIONS: These data suggest ESR1 variants are not associated with pan-CDK4/6i resistance and are consistent with the hypothesis that CDK4/6 blockade combined with a selective estrogen receptor degrader is potentially an effective option for ESR1m metastatic breast cancer.

Quantitative measurement of the ureter on three-dimensional magnetic resonance urography images using deep learning.

BACKGROUND: Accurate measurement of ureteral diameters plays a pivotal role in diagnosing and monitoring urinary tract obstruction (UTO). While three-dimensional magnetic resonance urography (3D MRU) represents a significant advancement in imaging, the traditional manual methods for assessing ureteral diameters are characterized by labor-intensive procedures and inherent variability. In the realm of medical image analysis, deep learning has led to a paradigm shift, yet the development of a comprehensive automated tool for the precise segmentation and measurement of ureters in MR images is an unaddressed challenge. PURPOSE: The ureter was quantitatively measured on 3D MRU images using a deep learning model. METHODS: A retrospective cohort of 445 3D MRU scans (443 patients, 52 ± 18 years; 217 female patients) was collected and split into training, validation, and internal testing cohorts. A 3D V-Net model was trained for urinary tract segmentation, and a post-processing algorithm was developed for ureteral measurements. The accuracy of the segmentation was evaluated using the Dice similarity coefficient (DSC) and volume intraclass correlation coefficient (ICC), with ground truth segmentations provided by experienced radiologists. The external cohort comprised 50 scans (50 patients, 55 ± 21 years; 30 female patients), and the model-predicted ureteral diameter measurements were compared with manual measurements to assess system performance. The various diameter parameters of ureter among the different measurement methods (ground truth, auto-segmentation with automatic diameter extraction, and manual segmentation with automatic diameter extraction) were assessed with Friedman tests and post hoc Dunn test. The effectiveness of the UTO diagnosis was assessed by receiver operating characteristic (ROC) curves and their respective areas under the curve (AUC) between different methods. RESULTS: In both the internal test and external cohorts, the mean DSC values for bilateral ureters exceeded 0.70. The ICCs for the bilateral ureter volume obtained by comparing the model and manual segmentation were all greater than 0.96 (p  < â€¯0.05), except for the right ureter in the internal test cohort, for which the ICC was 0.773 (p  < â€¯0.05). The mean DSCs for interobserver and intraobserver reliability were all above 0.97. The maximum diameter of the ureter exhibited no statistically significant differences either in the dilated (p = 0.08) or in the non-dilated (p = 0.32) ureters across the three measurement methods. The AUCs of ground truth, auto-segmentation with automatic diameter extraction, and manual segmentation with automatic diameter extraction in diagnosing UTO were 0.988 (95% CI: 0.934, 1.000), 0.961 (95% CI: 0.893, 0.991), and 0.979 (95% CI: 0.919, 0.998), respectively. There was no statistical difference between AUCs of the different methods (p > 0.05). CONCLUSION: The proposed deep learning model and post-processing algorithm provide an effective means for the quantitative evaluation of urinary diseases using 3D MRU images.

Real-World Treatment Patterns in Patients With HER2-Amplified Metastatic Colorectal Cancer: A Clinical-Genomic Database Study.

BACKGROUND: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there were no FDA-approved treatments. This study examined real-world treatment patterns in patients with HER2+ mCRC in the United States before and after the emerging awareness of HER2-directed therapies in 2018. METHODS: This was a retrospective observational study of patients with HER2+ mCRC from the GuardantINFORM database, which contains claims data for patients with Guardant360 genomic testing results. Patients were aged ≥18 years, were diagnosed with mCRC between January 2014 and September 2020, and had confirmed ERBB2 amplification via the blood-based Guardant360 test. Treatment patterns and real-world time to next treatment (rwTTNT) were evaluated. RESULTS: This study included 142 patients with a median age of 59 years; 31 (21.8%) patients with ERBB2 amplifications also had ERBB2 mutations. Treatment patterns were heterogeneous and evolved over time; before 2018, the most common regimen prescribed after detection of ERBB2 amplification was anti-VEGF therapy with or without chemotherapy (31.6%; n=25), and after 2018, HER2-directed therapies were the most commonly prescribed (36.5%; n=23). Median rwTTNT among the overall cohort was 8.4 months (95% CI, 6.5-10.0); rwTTNT was numerically longer in patients who received HER2-directed therapy compared with those who received non-HER2-directed therapies (11.0 months [95% CI, 6.3-12.3] vs 7.2 months [95% CI, 5.8-9.6]). CONCLUSIONS: This real-world study of the largest clinically annotated dataset of patients with HER2+ mCRC showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN Guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized. Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.

Open Linear Polymer Host-Guest Interactions Sensed by Luminescent Silver Nanodots.

The selectivity of the linear polymer chain toward its binding moieties has been considered negligible; thus, a clear demonstration showing the best-fit binding of a linear polymer to its guest counterpart is still unknown. Luminescent poly(acrylic acid) (PAA)-stabilized silver nanodots (PAA-AgNDs) have been applied as a turn-on sensor to monitor the interaction between the PAA chain and its binding cations. The binding of cations ions to the PAA chain may cross-link the linear PAA chain via coordination with carboxylate, which increases the rigidity of the polymer chain, retards the nonradiative decay of PAA-AgNDs, and consequently enhances the emission of silver nanodots while inducing a blue-shift of its emission spectrum. For the first time, we have demonstrated that a linear polymer chain can act as an open host to selectively bind to its best-matching cations. Specifically, among Group 2 cations (Mg2+, Ca2+, Sr2+, Ba2+), calcium ions show the strongest bonding to the PAA polymer chain. Our research suggests that, with extra rigidity, the polymer improves its chemical stability as calcium ions cross-linked the linear polymer. Meanwhile, it has also been demonstrated that luminescent silver nanodots can be excellent probes for the detection of polymer activities with straightforward and simple visualization methods.

Multiple epithelioid angiosarcoma of stomach and small intestine with multiple lymph node metastases: A case report.

RATIONALE: Angiosarcoma is a mesenchymal soft tissue sarcoma with a tendency for vascular endothelial differentiation. It is highly malignant with a poor prognosis but has a low incidence. Epithelioid angiosarcoma of the gastrointestinal tract is rare, and simultaneous multiple lesions of the stomach and small intestine are even rarer. It is easy to be misdiagnosed clinically. We report on a case of preoperative misdiagnosis of gastric cancer and postoperative diagnosis of epithelioid angiosarcoma with multiple lymph node metastases. PATIENT CONCERNS: A 75-year-old patient who was admitted to the hospital because of fatigue, melena and dysuria for >1 month. DIAGNOSIS, INTERVENTIONS AND OUTCOMES: Gastroscopy revealed gastric fundus ulcer and the biopsy revealed poorly differentiated adenocarcinoma of the fundus. We performed a radical gastrectomy for gastric cancer during which multiple ulcers were found in the jejunum and resected. Postoperative pathology showed multiple epithelioid angiosarcoma in the stomach and small intestine with lymph node metastases. The patient did not receive further treatment and died 2 month after the surgery. LESSONS: Gastrointestinal epithelioid angiosarcoma is one of the differential diagnoses of gastrointestinal adenocarcinoma and surgery is the main treatment. The lymph nodes are one of the main sites of metastasis.

Automatic measurement of the patellofemoral joint parameters in the Laurin view: a deep learning-based approach.

OBJECTIVES: To explore the performance of a deep learning-based algorithm for automatic patellofemoral joint (PFJ) parameter measurements from the Laurin view. METHODS: A total of 1431 consecutive Laurin views of the PFJ were retrospectively collected and divided into two parts: (1) the model development dataset (dataset 1, n = 1230) and (2) the hold-out test set (dataset 2, n = 201). Dataset 1 was used to develop the U-shaped fully convolutional network (U-Net) model to segment the landmarks of the PFJ. Based on the predicted landmarks, the PFJ parameters were calculated, including the sulcus angle (SA), congruence angle (CA), patellofemoral ratio (PFR), and lateral patellar tilt (LPT). Dataset 2 was used to assess the model performance. The mean of three radiologists who independently measured the PFJ parameters was defined as the reference standard. Model performance was assessed by the intraclass correlation coefficient (ICC), mean absolute difference (MAD), and root mean square (RMS) compared to the reference standard. Ninety-five percent limits of agreement (95% LoA) were calculated pairwise for each radiologist, reference standard, and model. RESULTS: Compared with the reference standard, U-Net showed good performance for predicting SA, CA, PFR, and LPT, with ICC = 0.85-0.97, MAD = 0.06-5.09, and RMS = 0.09-6.90 in the hold-out test set. Except for the PFR, the remaining parameters measured between the reference standard and the model were within the 95% LoA in the hold-out test dataset. CONCLUSIONS: The U-Net-based deep learning approach had a relatively high model performance in automatically measuring SA, CA, PFR, and LPT. KEY POINTS: • The U-Net model could be used to segment the landmarks of the PFJ and calculate the SA, CA, PFR, and LPT, which could be used to evaluate the patellar instability. • In the hold-out test, the automatic measurement model yielded comparable performance with reference standard. • The automatic measurement model could still accurately predict SA, CA, PFR, and LPT in patients with PI and/or PFOA.

Taurine-Upregulated Gene 1 Attenuates Cerebral Angiogenesis following Ischemic Stroke in Rats.

Objective: Angiogenesis is one of the therapeutic targets of cerebral infarction. Long noncoding RNAs (lncRNAs) can regulate the pathological process of angiogenesis following ischemic stroke. Taurine-upregulated gene 1 (TUG1), an lncRNA, is correlated to ischemic stroke. We intended to determine the effect of TUG1 on angiogenesis following an ischemic stroke. Materials and Methods: Middle cerebral artery occlusion (MCAO) was adopted to build a focal ischemic model of the rat brain, and pcDNA-TUG1 and miR-26a mimics were injected into rats. Neurological function was estimated through modified neurological severity scores. The volume of focal brain infarction was calculated through 2,3,5-triphenyltetrazolium chloride staining. The level of TUG1 and miR-26a was measured by PCR. The expression of vascular endothelial growth factor (VEGF) and CD31 was checked using immunohistochemistry and western blot. The correlation between miR-26a and TUG1 was verified through a luciferase reporter assay. Results: TUG1 increased noticeably while miR-26a was markedly reduced in MCAO rats. Overexpression of miR-26a improved neurological function recovery and enhanced cerebral angiogenesis in MCAO rats. TUG1 overexpression aggravated neurological deficits and suppressed cerebral angiogenesis in MCAO rats. Bioinformatics analysis revealed that miR-26a was one of the predicted targets of TUG1. Furthermore, TUG1 combined with miR-26a to regulate angiogenesis. TUG1 overexpression antagonized the role of miR-26a in neurological recovery and angiogenesis in MCAO rats. Conclusions: TUG1/miR-26a, which may act as a regulatory axis in angiogenesis following ischemic stroke, can be considered a potential target for cerebral infarction therapy.

Tuning the fast generation of luminescent silver nanodots on a surface.

Silver nanodots, predominantly a near-IR emitter, can be instantly generated on a surface by silver cluster transfer. Kinetic trapping of ssDNA molecules on the surface limits the reorganization of the resulting silver nanodots for other silver nanodot emitters. Adjusting the freedom of the adsorbed ssDNA can tune the generation of various silver nanodots on the surface.

Identification of a tripartite motif family gene signature for predicting the prognosis of patients with glioma.

Objectiove: The tripartite motif (TRIM) family genes, which encode a protein subfamily of the RING type E3 ubiquitin ligases, function as important regulators of oncogenesis and development. It is thus of great importance to investigate the potential value of the TRIM family genes for prognostic prediction in glioma. METHODS: The gene expression RNA-Seq data and corresponding clinical information of glioma patients were obtained from The Cancer Genome Atlas (TCGA) dataset and the Chinese Glioma Genome Atlas (CGGA) dataset. LASSO regression and multivariate Cox regression analyses were performed to construct a risk signature of the TRIM family genes. The accuracy of the risk signature in predicting the prognosis of glioma patients was evaluated. The effects of TRIM17 on glioma cell proliferation were further explored. RESULTS: We constructed a prognostic signature based on eight TRIMs for the prediction of overall survival of glioma patients. Internal and external cohorts confirmed the satisfactory accuracy and generalizability of the signature in predicting the prognosis of glioma patients. Of the eight TRIMs, TRIM17 was significantly downregulated in glioma, and decreased with an increase in the tumor grade. Moreover, low expression of TRIM17 predicted poor prognosis in glioma. CCK-8 and colony formation assays indicated that TRIM17 overexpression significantly inhibited cell proliferation. Conversely, silencing of TRIM17 had the opposite effects. CONCLUSION: Our eight-gene signature based on the TRIM gene family is a novel and clinically useful biomarker, which may be helpful for clinical decision-making. Additionally, TRIM17 might be a therapeutic target for glioma.

Shikonin attenuates kidney tubular epithelial cells apoptosis, oxidative stress, and inflammatory response through nicotinamide adenine dinucleotide phosphate oxidase 4/PTEN pathway in acute kidney injury of sepsis model.

Natural compounds were used in the treatment of acute kidney injury (AKI) caused by sepsis. This study investigated the function of shikonin from the roots of Arnebia purpurea in sepsis-induced AKI model. The target genes of shikonin were predicted by traditional Chinese medicine integrative database (TCMID). The markers of kidney injury, oxidative stress, and inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The pathological changes of kidney tubules were assessed by Hematoxylin and Eosin staining. Apoptosis of kidney tubular epithelial cells (KTECs) was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Protein expression was measured by western blot. Shikonin significantly improved kidney injury induced by cecal ligation and perforation (CLP). Besides, shikonin reduced KTECs apoptosis, malondialdehyde (MDA), reactive oxygen species (ROS), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) levels, while augmented SOD and IL-10 levels. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase4 (NOX4) was predicted a target gene of shikonin. The expression of NOX4 was significantly inhibited in shikonin-treated group and the levels of phosphatidylinositol 3,4,5-trisphosphate 3-phosphate and dual specificity protein phosphate (PTEN) and p-p65 were decreased, while level of p-Akt was elevated. In vitro experiments, shikonin inhibited cell apoptosis, inflammatory, and ROS in human HK-2 cells and rat TECs. Shikonin downregulated expression of NOX4, PTEN and p-p65, and upregulated p-AKT and Bcl-2 expression in HK2 cells treated with lipopolysaccharide (LPS). Moreover, overexpression of NOX4 enhanced the effect of LPS on the expression level of PTEN, p-p65, p-AKT, and Bcl-2, which was reversed by the addition of shikonin. Taken together, shikonin could improve sepsis-induced AKI in rats, and attenuate the LPS induced KTECs apoptosis, oxidative stress, and inflammatory reaction via modulating NOX4/PTEN/AKT pathway.

Clinicopathologic profiling and oncologic outcomes of secretory carcinoma of the breast.

Secretory carcinoma of the breast (SCB) is a rather rare entity of invasive breast cancer, the clinicopathologic characteristics and survival outcomes remain to be elaborated. A retrospective review was conducted in SEER database. A total of 190 SCB patients identified in SEER were eligible for inclusion in the analysis. Median age at diagnosis was 56 years (range 2-96 years). Both sexes and bilateral breast could be affected. Intriguingly, the incidence of SCB tended towards to decreasing in recent decades. Small tumor burden was observed with a mean tumor size of 2.13 cm. In a subgroup with sufficient details, positive staining of estrogen receptor (ER) and progesterone receptor (PR) was 58% and 40%, respectively. The vast majority of patients were of well to moderate differentiation (86.86%) and negative regional lymph nodes involvement (70.71%). Nearly half of the patients took radiotherapy and chemotherapy. Seniors were inclined to have an inferior breast cancer specific survival (BCSS) than their younger counterparts (P = 0.018). Patients underwent breast conserving surgery (BCS) and radiotherapy had much better BCSS than its mastectomy counterparts (P = 0.014). Collectively, SCB is a clinical indolent invasive breast cancer with excellent prognosis. BCS in conjunction with radiotherapy would be a rational alternative for this distinct entity.

Prognostic and clinicopathological significance of C-reactive protein/albumin ratio (CAR) in patients with gastric cancer: A meta-analysis.

BACKGROUND: In recent years, many studies have explored the potential prognostic utility of C-reactive protein/albumin ratio (CAR) in patients with gastric cancer (GC), however, the results remain conflicting. We thus performed a meta-analysis to determine the association of CAR and prognosis of GC. METHODS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. PubMed, Web of science, Embase, and Cochrane Library were searched. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and cancer-specific survival (CSS) of included studies were pooled to estimate the prognostic value of CAR. RESULTS: Eight studies with a total of 3,216 patients were included in this meta-analysis. High CAR was significantly associated with poor OS (HR = 1.59, 95%CI = 1.36-1.85, p<0.001) and worse CSS (HR = 1.65, 95%CI = 1.21-2.25, p = 0.002). In addition, high CAR was significantly associated with male sex (OR = 1.80, 95%CI = 1.31-2.47, p<0.001), advanced tumor stage (OR = 2.14, 95%CI = 1.48-3.09, p<0.001), and tumor size ≥3cm (OR = 2.69, 95%CI = 1.84-3.93, p<0.001). CONCLUSION: Elevated pretreatment CAR is a prognostic marker of poor OS and CSS in patients with GC. Furthermore, high CAR levels are associated with clinicopathological features reflecting tumor progression.

When there is a will there is a way: The role of proactive personality in combating COVID-19.

The global COVID-19 pandemic has disrupted personal and work lives and created great uncertainty and stress, especially for frontline health care professionals like doctors and nurses who risk personal health while facing increased workloads and new COVID-related tasks. People can passively respond to this disruption, or they can be more active and choose to shape the conditions surrounding their work during the crisis. We designed a multiwave, multisource study examining whether a proactive orientation is a key resource for frontline health care professionals in the COVID-19 pandemic. Drawing from proactive and conservation of resources theories, we studied a sample of 408 doctors and nurses at a COVID-19 hospital in the locked-down area surrounding Wuhan City, China during the first wave of the virus. Our aim is to examine how personal agency contributes to health care professionals' performance and well-being when combating COVID-19. Proactive personality as a dispositional resource was associated with higher levels of perceived strengths use, a job-related motivational resource. This effect was jointly moderated by routine disruption and perceived organizational support. Proactive personality was indirectly associated with performance and two indicators of well-being (resilience and thriving) through perceived strengths use. More frequent physical exposure to the virus magnified the effects of perceived strengths use on an archival indicator of performance during the first wave of the pandemic. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Use of a gentamicin-citrate lock leads to lower catheter-related bloodstream infection rates and reduced cost of care in hemodialysis patients.

INTRODUCTION: Central venous catheters (CVC) are a major contributor to infections in hemodialysis (HD) patients, leading to high morbidity and mortality. Gentamicin-citrate (GC) lock is used as standard of care at centers belonging to a mid-size dialysis organization. Four outpatient HD centers acquired by the organization continued to use heparin for catheter locks for a period of time before converting to the provider's standard of using GC lock. METHODS: In this retrospective observational study, we included patients receiving HD by CVC at these four centers. We report rates of CVC-related bloodstream infections (CVC-BSI) during the heparin lock and the GC lock periods; crude rate ratios and adjusted rate ratios using Cox survival analyses adjusting for potential confounders; microbiology patterns; safety signals (gentamicin resistance, hospitalizations and deaths); and financial impact on payer. FINDINGS: A total of 220 and 281 patients used tunneled CVCs, accounting for 25,245 and 44,550 catheter days in the heparin and the GC lock periods, respectively. CVC-BSI event rates were 66% lower in the GC lock period (CVC-BSI event rate: 0.20 per 1000 catheter-days) than the heparin lock period (rate: 0.59 per 1000 catheter days); rate ratio 0.34 (95% confidence interval (CI) 0.15-0.78, P = 0.01). In the fully adjusted multivariable Cox model, use of GC lock was associated with 70% reduction in CVC-BSI events (HR 0.30, 95% CI 0.12-0.72, P = 0.01). No increased risk of gentamicin resistance, hospitalizations, or death associated with use of GC lock were observed. Use of GC lock was associated with an estimated saving of $1533 (95% CI: $259-$4882) per patient per year. DISCUSSION: Use of GC lock led to significant reductions in CVC-BSIs with no signal for harm, and is associated with significant cost savings in dialysis care.

Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size.

BACKGROUND: Since December 2019, COVID-19 has spread to almost every corner of the world. In theory, tocilizumab and favipiravir are considered to be reliable drugs for the treatment of COVID-19 with elevated IL-6. We aimed to assess the efficacy and safety of tocilizumab combined with favipiravir in patients with COVID-19. METHODS: This was a multicenter trial in adults with COVID-19. Patients were randomly assigned (3:1:1) to a 14-day combination of favipiravir combined with tocilizumab (combination group), favipiravir, and tocilizumab. The primary outcome was the cumulative lung lesion remission rate (lung CT examination indicated absorption of lung inflammation). RESULTS: Between Feb 2 and March 15, 2020, 26 patients were recruited; 14 were randomly assigned to the combination group, 7 were assigned to the favipiravir group and 5 were assigned to the tocilizumab group. The cumulative lung lesion remission rate at day 14 was significantly higher in combination group as compared with favipiravir group (P = 0.019, HR 2.66 95 % CI [1.08-6.53]). And there was also a significant difference between tocilizumab and favipivavir (P = 0.034, HR 3.16, 95 % CI 0.62-16.10). In addition, there was no significant difference between the combination group and the tocilizumab group (P = 0.575, HR 1.28 95 %CI 0.39-4.23). Furthermore, combined therapy can also significantly relieve clinical symptoms and help blood routine to return to normal. No serious adverse events were reported. CONCLUSION: Tocilizumab combined with or without favipiravir can effectively improve the pulmonary inflammation of COVID-19 patients and inhibit the deterioration of the disease.

In Situ Generated Silver Nanodot Förster Resonance Energy Transfer Pair Reveals Nanocage Sizes.

Characterizing nanocages in macromolecules is one of the keys to understanding various biological activities and further utilizing nanocages for novel materials synthesis. However, fast and straightforward detection of the nanocage size remains challenging. Here, we present a new approach to detect the diameter of a nanocage by Förster resonance energy transfer (FRET) of luminescent silver nanodot pairs with reverse micelles as a model. Silver nanodot FRET pairs can be generated in situ from a single silver nanodot species with critical energy transfer distances, R0, of 4.8-6.5 nm. We have applied this approach to clarify the size variation of the water nanocage in nonionic surfactant Triton X-100-based reverse micelles. FRET efficiency decreases as more water is added, indicating that the size of the reverse micelles continuously expands with water content. The silver element in the nanocage also enhances the visualization of the nanocage under cryo-TEM imaging. The diameter of the water nanocage measured with the above approach is consistent with that obtained by cryo-TEM, demonstrating that the FRET measurement of silver nanodots can be a fast and accurate tool to detect nanocage dimensions. The above demonstration allows us to apply our strategy to other protein-based nanocages.

The effects of laughter therapy on depression symptoms in patients undergoing center hemodialysis: A pragmatic randomized controlled trial.

INTRODUCTION: People with end-stage renal disease undergoing hemodialysis are at increased risk for stress, anxiety, and depression. The study objective was to measure the effect of intradialytic group laughter therapy on depressive symptoms in people on hemodialysis (HD). METHODS: Pragmatic randomized controlled trial conducted with prevalent HD patients in 10 centers in Northern California. The intervention group received a once weekly, 30-minute group laughter therapy session for 8 weeks. Primary outcome was the number of people with depressive symptoms as measured using the four Item Patient Health Questionnaire. Secondary outcomes were anxiety, subjective well-being, and patient-reported outcome measures. FINDINGS: In all, 151 participants completed both predepression and postdepression symptom measures (72 intervention and 79 control). The proportion of patients with self-reported depressive symptoms changed from 17 (22%) to 16 (20%), in the control and from 11 (17%) to 5 (8%) in the intervention arms, respectively (P = 0.04). In the control arm, 7 out of the 17 patients with self-reported depressive symptoms at baseline continued to report depressive symptoms at follow up compared to the intervention arm where only 1 of 12 patients continued to report depressive symptoms. No differences were noted between the groups for reported anxiety, patient-reported dialysis symptoms, and subjective well-being. DISCUSSION: This study found intradialytic group laughter can decrease the number of people with depressive symptoms receiving hemodialysis. Larger and long-term studies are required to evaluate the effect of intradialytic laughter on patient related outcomes and quality of life.

Oncogenic microRNA-765 promotes the growth and metastasis of breast carcinoma by directly targeting ING4.

Previous investigations have proved that microRNA (miR)-765 is significantly overexpressed in multiple tumor types. Nevertheless, the underlying molecular mechanism of miR-765 in mediating breast carcinoma cell growth and metastasis remains unclear. Quantitative real-time polymerase chain reaction was used to determine the levels of miR-765 and inhibitor of growth 4 (ING4) in breast carcinoma tissues and breast carcinoma cells. Cell proliferation, colony formation, wound healing, and Transwell invasion assays were used to analysis the role of miR-765 on breast carcinoma cell growth and aggressiveness. The expressions of ING4 were determined using Western blot analysis and immunohistochemical staining. The direct target of ING4 and miR-765 was confirmed using the luciferase reporter assay. Nude mice were subcutaneously implanted with miR-765 inhibitor transfected MDA-MB-231 cells to determine the potential role of miR-765 in tumor growth in vivo. We observed that miR-765 is overexpressed in breast carcinoma tissue and breast cancer cells. By using luciferase reporter gene bioassay, we find that ING4 is the direct target of miR-765 in breast carcinoma. The level of ING4 is inversely associated with the level of miR-765. The gain-of-function and loss-of-function experiments in vitro indicate that the downregulation of miR-765 suppresses the growth, mobility, and invasion abilities of breast cancer cells by inhibiting ING4. In addition, overexpression of ING4 suppresses the aggressiveness of the MDA-BA-231 cell that is induced by miR-761 in vitro. In this study, we prove that miR-765 regulates the growth and metastasis of breast cancer via modulating miR-765-ING4-negative feedback loop.