Carbon quantum dots of ginsenoside Rb1 for application in a mouse model of intracerebral Hemorrhage.

After intracerebral hemorrhage (ICH) occurs, the overproduction of reactive oxygen species (ROS) and iron ion overload are the leading causes of secondary damage. Removing excess iron ions and ROS in the meningeal system can effectively alleviate the secondary damage after ICH. This study synthesized ginsenoside Rb1 carbon quantum dots (RBCQDs) using ginsenoside Rb1 and ethylenediamine via a hydrothermal method. RBCQDs exhibit potent capabilities in scavenging ABTS + free radicals and iron ions in solution. After intrathecal injection, the distribution of RBCQDs is predominantly localized in the subarachnoid space. RBCQDs can eliminate ROS and chelate iron ions within the meningeal system. Treatment with RBCQDs significantly improves blood flow in the meningeal system, effectively protecting dying neurons, improving neurological function, and providing a new therapeutic approach for the clinical treatment of ICH.

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG).

N1-methyladenosine (m1A) modification is a crucial post-transcriptional regulatory mechanism of messenger RNA (mRNA) in living organisms. Few studies have focused on analysis of m1A regulators in lower-grade gliomas (LGG). We employed the Nonnegative Matrix Factorization (NMF) technique on The Cancer Genome Atlas (TCGA) dataset to categorize LGG patients into 2 groups. These groups exhibited substantial disparities in terms of both overall survival (OS) and levels of infiltrating immune cells. We collected the significantly differentially expressed immune-related genes between the 2 clusters, and performed LASSO regression analysis to obtain m1AScores, and established an m1A-related immune-related gene signature (m1A-RIGS). Next, we categorized all patients with LGG into high- and low-risk subgroups, predictive significance of m1AScore was confirmed by conducting univariate/multivariate Cox regression analyses. Additionally, we confirmed variations in immune-related cells and ssGSEA and among the high-/low-risk subcategories in the TCGA dataset. Finally, our study characterized the effects of MSR1 and BIRC5 on LGG cells utilizing Edu assay and flow cytometry to explore the effects of modulation of these genes on glioma. The results of this study suggested that m1A-RIGS may be an excellent prognostic indicator for patients with LGG, and could also promote development of novel immune-based treatment strategies for LGG. Additionally, BIRC5 and MSR1 may be potential therapeutic targets for LGG.

Dominant dystrophic epidermolysis bullosa is associated with glycolytically active GATA3+ Th2 cells which may contribute to pruritus in lesional skin.

BACKGROUND: Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined. OBJECTIVE: To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients. METHODS: We evaluated affected and unaffected skin biopsy samples from 6 DDEB subjects (all with the very itchy pruriginosa subtype), and 4 healthy individuals using bulk RNA-seq. Single-cell transcriptomes of affected (n=2) and unaffected (n=1) DDEB and healthy skin (n=2) were obtained. Dupilumab treatment was provided for three patients. RESULTS: The skin bulk transcriptome showed significant enrichment of Th1/2 and Th17 pathways in affected DDEB skin compared with non-lesional DDEB and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3+ Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced VAS itch scores after 12 weeks (mean VAS=3.83) compared to pre-treatment (mean VAS=7.83). Bulk RNA-seq and qPCR showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin show very similar transcriptomic profiles, and reduced Th1/2 and Th17 pathway enrichment. CONCLUSIONS: Single-cell RNA-seq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus.

A pilot trial of neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer.

Triple-positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan-human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin-dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II-III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%-84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0-I was 75% (95% CI, 46.8%-91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5%-70.5%) at baseline to 17.2% (95% CI, 0.7%-33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment-related deaths occurred. This four-drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

Self-improving dystrophic epidermolysis bullosa with a novel heterozygous missense variant in the COL7A1 gene in a Taiwanese family.

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

Aryl hydrocarbon receptor: Linking environment to aging process in elderly patients with asthma.

ABSTRACT: Aging is a significant risk factor for various diseases, including asthma, and it often leads to poorer clinical outcomes, particularly in elderly individuals. It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage, resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases. The effects of aging affect not only the elderly but also those of younger ages, posing significant challenges to global healthcare. Thus, understanding the molecular mechanisms associated with aging in different diseases is essential. One intriguing factor is the aryl hydrocarbon receptor (AhR), which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process. Here, we review the literature on several major hallmarks of aging, including mitochondrial dysfunction, cellular senescence, autophagy, mitophagy, epigenetic alterations, and microbiome disturbances. Moreover, we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures, particularly in relation to the immune system. Furthermore, we explore how aging hallmarks affect clinical characteristics, inflammatory features, exacerbations, and the treatment of asthma. It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

Integration of the cancer cell secretome and transcriptome reveals potential noninvasive diagnostic markers for bladder cancer.

PURPOSE: Bladder cancer (BLCA) is a major cancer of the genitourinary system. Although cystoscopy is the standard protocol for diagnosing BLCA clinically, this procedure is invasive and expensive. Several urine-based markers for BLCA have been identified and investigated, but none has shown sufficient sensitivity and specificity. These observations underscore the importance of discovering novel BLCA biomarkers and developing a noninvasive method for detection of BLCA. Exploring the cancer secretome is a good starting point for the development of noninvasive biomarkers for cancer diagnosis. EXPERIMENTAL DESIGN: In this study, we established a comprehensive secretome dataset of five representative BLCA cell lines, BFTC905, TSGH8301, 5637, MGH-U1, and MGH-U4, by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression of BLCA-specific secreted proteins at the transcription level was evaluated using the Oncomine cancer microarray database. RESULTS: The expressions of four candidates-COMT, EWSR1, FUSIP1, and TNPO2-were further validated in clinical human specimens. Immunohistochemical analyses confirmed that transportin-2 was highly expressed in tumor cells relative to adjacent noncancerous cells in clinical tissue specimens from BLCA patients, and was significantly elevated in BLCA urine compared with that in urine samples from aged-matched hernia patients (controls). CONCLUSIONS: Collectively, our findings suggest TNPO2 as a potential noninvasive tumor-stage or grade discriminator for BLCA management.

Reclaimed seawater discharge - Desalination brine treatment and resource recovery system.

With the proliferation of reverse osmosis technology, seawater reverse osmosis desalination has been heralded as the solution to water scarcity for coastal regions. However, the large volume of desalination brine produced may pose an adverse environmental impact when directly discharged into the sea and result in energy wastage as the seawater pumped out is dumped back into the sea. Recently, zero liquid discharge has been extensively studied as a way to eliminate the aquatic ecotoxicity impact completely, despite being expensive and having a high carbon footprint. In this work, we propose a new strategy towards the treatment of brine to seawater level for disposal, dubbed reclaimed seawater discharge (RSD). This process is coupled with existing resource recovery techniques and waste alkali CO2 capture processes to produce an economically viable waste treatment process with minimal CO2 emissions. In this work, we placed significant focus on the electrolysis of brine, which simultaneously lowers the salinity of the desalination brine (56.0 ± 2.1 g/L) to seawater level (32.0 ± 1.4 g/L), generates alkali brine from seawater (pH 13.6) to remove impurities in brine (Mg2+ and Ca2+ to below ppm level), and recovers magnesium hydroxide, calcium carbonate, chlorine, bromine, and hydrogen gas as valuable resources. The RSD is further chemically dechlorinated and neutralised to pH 7.3 to be safe to discharge into the sea. The excess alkali brine is used to capture additional CO2 in the form of bicarbonates, achieving net abatement in climate change impact (9.90 CO2 e/m3) after product carbon abatements are accounted.

Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer.

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan-Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3-5) to 11 months (95% CI 8-12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38-50) and 25% (95 CI 20-30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19-29) and 6% (95 CI 3-9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88-2.72, p value < 0.001) was an adverse independent prognostic factor for patients. This study concludes that CDS prolonged survival in patients with gastric cancer with liver metastases. Due to the lack of information on the quality of life, biomarkers, targeted therapies, and immunotherapy in the SEER database, the observed improved survival rates following CDS of hepatic metastasis from gastric cancer requires prospective studies that take these factors into account to properly address the survival advantages and impact on quality of life of such a method.

A novel link between melatonin and circ_0005753/PTBP1/TXNIP regulatory network in the modulation of osteogenic potential in mesenchymal stem cells.

Labeled with pluripotent potential, the transplantation of bone marrow mesenchymal stem cells (BMSCs) is considered as a promising strategy for treating osteoporosis (OP). Melatonin (MEL) has been investigated to be an essential regulator involved in bone metabolism, as well as BMSCs differentiation. Circular RNAs (circRNAs) are a unique kind of non-coding RNA and play an important regulatory role in OP. However, whether circRNAs are implicated in the effects of MEL on BMSCs osteogenic differentiation remains largely indeterminate. Expression of circ_0005753 in human BMSCs with MEL treatment, clinical specimens diagnosed with OP, either with ovariectomy (OVX)-induced mice, was measured by RT-qPCR. Western blot was conducted to analyze protein levels of osteogenesis-related molecules (Opg, RUNX2, ALP, BMP4) and TXNIP. RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to validate the binding relationship among circ_0005753, PTBP1, and TXNIP. Alkaline phosphatase (ALP) and alizarin red staining (ARS) were performed to evaluate osteogenic capacity of BMSCs. OP mouse model was established by ovariectomy, as evaluated pathologic changes via hematoxylin-eosin (HE), Masson, and Immunohistochemistry (IHC) staining. Expression of circ_0005753 was remarkably decreased during MEL-induced osteogenic differentiation of BMSCs. Interestingly, not only circ_0005753 knockdown significantly promoted osteogenic differentiation of BMSCs, but circ_0005753 overexpression also weakened osteogenic differentiation induced by MEL treatment. Mechanistically, circ_0005753 maintained the stabilization of TXNIP mRNA via recruiting PTBP1. Additionally, reinforced circ_0005753 abrogated MEL-mediated protective effects on OP pathogenesis in a mouse model. This work shows that MEL facilitates osteogenic differentiation of BMSCs via the circ_0005753/PTBP1/TXNIP axis, which may shed light on the development of a novel therapeutic strategy to prevent OP.

Polyolefin-derived substrate-grown carbon nanotubes as binder-free electrode for hydrogen evolution in alkaline media.

Switching from a linear mode of waste management to a circular loop by transforming plastic waste into carbon nanotubes (CNTs) is a promising approach to current plastic waste treatment. One of the many applications of CNTs is its use for electrocatalytic water splitting for hydrogen evolution. Existing methods of CNTs-based hydrogen evolution reaction (HER) electrode fabrication involve additives like polymeric binders and additional steps to improve CNT dispersion, which are detrimental to the CNT structure and properties. The in-situ fabrication approach can potentially be a one-pot solution to HER electrode synthesis. In this study, polyolefins pyrolysis gas and a Co:Ni:Mg catalyst were used to fabricate binder-free CNTs-based electrodes on different substrates for HER. The study assessed CNT quality on conductive carbon paper, semiconductive silicon, and dielectric glass substrates, evaluating their HER performance in 1 M KOH. A mixture of hollow-core, bamboo-like, and cup-stacked arrangement nanotubes were synthesized on the substrates, with CNTs on glass and carbon paper substrates possessing better graphitization than CNTs grown on silicon. This is in agreement with HER performance, whereby the as-prepared electrodes required overpotentials of 267 mV, 241 mV, and 216 mV for silicon, glass, and carbon paper, respectively, to achieve 10 mA/cm2. Despite being poorly conductive, the glass substrate electrode achieved a lower overpotential than the silicon electrode. Additionally, the as-prepared silicon electrode faced a delamination issue likely attributed to the lower surface energy of the silicon substrate surface, demonstrating the weaker adhesion between the CNTs and silicon surface. The proposed approach thus showed that the in-situ fabricated electrodes performed better than separately synthesized CNTs prepared into electrodes by 27.4% and 14.2% for carbon paper and glass substrates, respectively. The improved performance of the as-prepared, binder-free electrodes can be linked to the lower charge-transfer resistance and reduced contact resistance between the CNTs and substrate.

Effective delivery of miR-511-3p with mannose-decorated exosomes with RNA nanoparticles confers protection against asthma.

Our previous studies have shown that miR-511-3p treatment has a beneficial effect in alleviating allergic airway inflammation. Here, we sought to explore its therapeutic potential in animal models and gain a deeper understanding of its therapeutic value for asthma. miR-511-3p knockout mice (miR-511-3p-/-) were generated by CRISPR/Cas and showed exacerbated airway hyper-responsiveness and Th2-associated allergic airway inflammation compared with wild-type (WT) mice after exposed to cockroach allergen. RNA nanoparticles with mannose decorated EV-miR-511-3p were also created by loading miR-511-3p mimics into the mannose decorated EVs with engineered RNA nanoparticle PRNA-3WJ (Man-EV-miR-511-3p). Intra-tracheal inhalation of Man-EV-miR-511-3p, which could effectively penetrate the airway mucus barrier and deliver functional miR-511-3p to lung macrophages, successfully reversed the increased airway inflammation observed in miR-511-3p-/- mice. Through microarray analysis, complement C3 (C3) was identified as one of the major targets of miR-511-3p. C3 was increased in LPS-treated macrophages but decreased after miR-511-3p treatment. Consistent with these findings, C3 expression was elevated in the lung macrophages of an asthma mouse model but decreased in mice treated with miR-511-3p. Further experiments, including miRNA-mRNA pulldown and luciferase reporter assays, confirmed that miR-511-3p directly binds to C3 and activates the C3 gene. Thus, miR-511-3p represents a promising therapeutic target for asthma, and RNA nanotechnology reprogrammed EVs are efficient carriers for miRNA delivery for disease treatment.

GLI1+ perivascular, renal, progenitor cells: The likely source of spontaneous neoplasia that created the AGMK1-9T7 cell line.

The AGMK1-9T7 cell line has been used to study neoplasia in tissue culture. By passage in cell culture, these cells evolved to become tumorigenic and metastatic in immunodeficient mice at passage 40. Of the 20 x 106 kidney cells originally plated, less than 2% formed the colonies that evolved to create this cell line. These cells could be the progeny of some type of kidney progenitor cells. To characterize these cells, we documented their renal lineage by their expression of PAX-2 and MIOX, detected by indirect immunofluorescence. These cells assessed by flow-cytometry expressed high levels of CD44, CD73, CD105, Sca-1, and GLI1 across all passages tested; these markers have been reported to be expressed by renal progenitor cells. The expression of GLI1 was confirmed by immunofluorescence and western blot analysis. Cells from passages 13 to 23 possessed the ability to differentiate into adipocytes, osteoblasts, and chondrocytes; after passage 23, their ability to form these cell types was lost. These data indicate that the cells that formed the AGMK1-9T7 cell line were GLI1+ perivascular, kidney, progenitor cells.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial.

BACKGROUND: Pleural mesothelioma usually presents at an advanced, incurable stage. Chemotherapy with platinum-pemetrexed is a standard treatment. We hypothesised that the addition of pembrolizumab to platinum-pemetrexed would improve overall survival in patients with pleural mesothelioma. METHODS: We did this open-label, international, randomised phase 3 trial at 51 hospitals in Canada, Italy, and France. Eligible participants were aged 18 years or older, with previously untreated advanced pleural mesothelioma, with an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) to intravenous chemotherapy (cisplatin [75 mg/m2] or carboplatin [area under the concentration-time curve 5-6 mg/mL per min] with pemetrexed 500 mg/m2, every 3 weeks for up to 6 cycles), with or without intravenous pembrolizumab 200 mg every 3 weeks (up to 2 years). The primary endpoint was overall survival in all randomly assigned patients; safety was assessed in all randomly assigned patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02784171, and is closed to accrual. FINDINGS: Between Jan 31, 2017, and Sept 4, 2020, 440 patients were enrolled and randomly assigned to chemotherapy alone (n=218) or chemotherapy with pembrolizumab (n=222). 333 (76 %) of patients were male, 347 (79%) were White, and median age was 71 years (IQR 66-75). At final analysis (database lock Dec 15, 2022), with a median follow-up of 16·2 months (IQR 8·3-27·8), overall survival was significantly longer with pembrolizumab (median overall survival 17·3 months [95% CI 14·4-21·3] with pembrolizumab vs 16·1 months [13·1-18·2] with chemotherapy alone, hazard ratio for death 0·79; 95% CI 0·64-0·98, two-sided p=0·0324). 3-year overall survival rate was 25% (95% CI 20-33%) with pembrolizumab and 17% (13-24%) with chemotherapy alone. Adverse events related to study treatment of grade 3 or 4 occurred in 60 (27%) of 222 patients in the pembrolizumab group and 32 (15%) of 211 patients in the chemotherapy alone group. Hospital admissions for serious adverse events related to one or more study drugs were reported in 40 (18%) of 222 patients in the pembrolizumab group and 12 (6%) of 211 patients in the chemotherapy alone group. Grade 5 adverse events related to one or more drugs occurred in two patients on the pembrolizumab group and one patient in the chemotherapy alone group. INTERPRETATION: In patients with advanced pleural mesothelioma, the addition of pembrolizumab to standard platinum-pemetrexed chemotherapy was tolerable and resulted in a significant improvement in overall survival. This regimen is a new treatment option for previously untreated advanced pleural mesothelioma. FUNDING: The Canadian Cancer Society and Merck & Co.

Evaluating the sensitivity of newborn rats and newborn hamsters to oncogenic DNA.

To evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cell lines, we have been establishing in vivo assays to quantify the oncogenic activity of DNA. We had generated three oncogene-expression plasmids: pMSV-T24-H-ras, which expresses activated H-ras; pMSV-c-myc, which expresses c-myc; and pMSV-T24-H-ras/MSV-c-myc, which expresses both oncogenes. Tumors were induced in mice by pMSV-T24-H-ras plus pMSV-c-myc or by pMSV-T24-H-ras/MSV-c-myc. Because newborn hamsters and newborn rats have been recommended for oncogenicity testing of the DNA from tumorigenic mammalian cell-substrates used for vaccine production, we evaluated their sensitivity. Newborn hamsters and rats were inoculated with different doses of pMSV-T24-H-ras/MSV-c-myc to determine their sensitivity to tumor induction and with the single-oncogene-expression plasmids to determine whether single oncogenes could induce tumors. Newborn rats were more sensitive than newborn hamsters, and activated H-ras but not c-myc induced tumors in newborns of both rodent species. DNA from four cell lines established from tumors induced by pMSV-T24-H-ras/MSV-c-myc was inoculated into newborn rats. Because no tumors were induced by this cellular DNA, which should be optimal as it contains both oncogenes linked and present in several copies, we conclude that available in vivo models are not sensitive enough to detect the oncogenicity of cellular DNA.

Influence of stone load on the outcome of same-session flexible ureteroscopy for bilateral upper urinary tract stones: a multicenter retrospective study.

Purpose: This study aimed to evaluate the efficacy and safety of same-session flexible ureteroscopy (fURS) for the treatment of bilateral upper urinary tract stones and to examine the influence of stone load on the outcome of same-session fURS, stratifying by total diameter of stones (TDS) ≤30 mm vs. >30 mm. Patients and methods: We retrospectively reviewed all cases of same-session fURS performed for bilateral upper urinary tract stones at four institutions between January 2017 and September 2020. All patients were divided into two groups based on TDS, ≤30 mm and >30 mm. Data on patient demographics, stone characteristics, surgical results, and complications were collected and analyzed for differences between the two groups. Stone-free rate (SFR) was defined as patients endoscopically stone-free or with radiological fragments <2 mm of each renal unit. Results: A total of 121 patients with bilateral upper urinary tract stones underwent same-session fURS, consisting of 73 patients in the TDS ≤ 30 mm group and 48 patients in the TDS > 30 mm group. The mean bilateral stone size was 28.2 ± 12.2 mm (range: 9.1-38.4 mm), with a mean operating time of 97.1 ± 39.6 min (range: 19-220 min). The SFR was 54.5% after the first fURS, and SFR increased to 97.5% after re-fURS for residual stones. The operation time for the TDS > 30 mm group was longer than that of the TDS ≤ 30 mm group (85.1 ± 36.5 vs. 115.4 ± 37.4 min, p < 0.001). The SFR after the first fURS was significantly lower in the TDS > 30 mm group than in the TDS ≤ 30 mm group (25.0% vs. 73.9%, p < 0.001). Although there was no statistically significant difference in overall SFR between the two groups (93.7% vs. 100%, p = 0.060), the rate of re-fURS for residual stones was higher in the TDS > 30 mm group than in the TDS ≤ 30 mm group (75% vs. 26%, p < 0.001). There were no significant differences in length of hospital stay (LOS) (2.2 ± 0.7 vs. 2.3 ± 1.0, p = 0.329) or complication rate (10.9% vs. 14.6%, p = 0.582) between the two groups. Conclusion: The results suggested that same-session fURS can be effectively performed with a low complication rate. A higher SFR after the first fURS can be achieved in the case of bilateral upper urinary tract stones with TDS ≤ 30 mm, and priority should be given to same-session fURS.

Does the Effect of Stress on Smartphone Addiction Vary Depending on the Gender and Type of Addiction?

Stress is closely associated with smartphone addiction. Nevertheless, there is a dearth of studies investigating the potential variation in the effect of stress on smartphone addiction based on the specific addiction type and gender. We conducted a cross-sectional questionnaire survey among 596 high school students. The results revealed that the effect size of stress on smartphone addiction varied across different types of addiction. The strongest relationship was observed between stress and social media addiction, followed by the relationship between stress and information acquisition addiction. Furthermore, gender played a significant moderating role in stress and three types of smartphone addiction. Specifically, stress was strongly associated with information acquisition addiction overall, with no significant gender differences observed. In contrast, stress exhibited a strong correlation with social media addiction, which was significantly more prevalent among females. On the other hand, game addiction and short-form video addiction were both strongly associated with stress, but showed significantly higher prevalence among males. This study enhances current research by offering supplementary insights into the correlation between stress and smartphone addiction, as well as exploring the potential implications of intervening in smartphone addiction.

Multiple Itchy Erythematous Papules and Plaques Localized to 1 Shin.

A woman in her 30s presented with progressive, multiple itchy erythematous to violaceous papules and plaques with milia and a few erosions with partially detached epidermis localized to the left shin. What is your diagnosis?