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Plasmacytoid urothelial carcinoma (PUC) is an extremely rare and aggressive variant of urothelial carcinoma. We report a case of a 62-year-old male who presented with a rapid spread of PUC to involve his entire scrotal wall after failed surgery and chemotherapy. The second course of chemotherapy was effective in providing symptom control. We believe this is the first case report of PUC causing such rapid and extensive scrotal invasion. This case highlights the important features of PUC including the pattern of tumor spread along fascial planes, the tendency for initial understaging, and the rapid recurrence after initially response to chemotherapy.

Aims: This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods: The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results: A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion: The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets. Cite this article: Bone Joint Res 2023;12(9):522–535.

Abstract Background While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine. Methods We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes. Results We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine. Conclusions Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine.

This paper proposed a high-sensitivity phase imaging eddy current magneto-optical (PI-ECMO) system for carbon fiber reinforced polymer (CFRP) defect detection. In contrast to other eddy current-based detection systems, the proposed system employs a fixed position excitation coil while enabling the detection point to move within the detection region. This configuration effectively mitigates the interference caused by the lift-off effect, which is commonly observed in systems with moving excitation coils. Correspondingly, the relationship between the defect characteristics (orientation and position) and the surface vertical magnetic field distribution (amplitude and phase) is studied in detail by theoretical analysis and numerical simulations. Experiments conducted on woven CFRP plates demonstrate that the designed PI-ECMO system is capable of effectively detecting both surface and internal cracks, as well as impact defects. The excitation current is significantly reduced compared with traditional eddy current magneto-optical (ECMO) systems.

ObjectiveThe brain compensation mechanism in postoperative delirium (POD) has not been reported. We uncovered the mechanism by exploring the association between POD and glioma grades, and the relationship between preoperative brain structural and functional compensation with POD in patients with frontal glioma.MethodsA total of 335 adult patients with glioma were included. The multivariable analysis examined the association between tumor grade and POD. Then, 20 patients with left frontal lobe glioma who had presurgical structural and functional MRI data and Montreal Cognitive Assessment (MoCA) in this cohort were analyzed. We measured the gray matter volume (GMV) and functional connectivity (FC) in patients with (n = 8) and without (n = 12) POD and healthy controls (HCs, n = 29) to detect the correlation between the structural and functional alteration and POD.ResultsThe incidence of POD was 37.3%. Multivariable regression revealed that high-grade glioma had approximately six times the odds of POD. Neuroimaging data showed that compared with HC, the patients with left frontal lobe glioma showed significantly increased GMV of the right dorsal lateral prefrontal cortex (DLPFC) in the non-POD group and decreased GMV of right DLPFC in the POD group, and the POD group exhibited significantly decreased FC of right DLPFC, and the non-POD group showed the increasing tendency. Partial correlation analysis showed that GMV in contralesional DLPFC were positively correlated with preoperative neurocognition, and the GMV and FC in contralesional DLPFC were negatively correlated with POD.ConclusionsOur findings suggested that insufficient compensation for injured brain regions involving cognition might be more vulnerable to suffering from POD.

Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of cardiovascular diseases in clinic. The present study was designed to clarify the effects of NXT on haemorheology, blood coagulation, hepatic function, antioxidant capacity and inflammatory responses in a rat model of blood stasis syndrome. Rats were placed in ice-cold water for 5 min during the time interval of two adrenaline injections to induce blood circulation disorders after intragastric administration of 10 consecutive days. Blood was collected from abdominal aorta to determine whole blood viscosity (WBV), plasma viscosity (PV), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), malonaldehyde (MDA), alanine transaminase (ALT), aspartate transaminase (AST), interleukin-1β (IL-1β), interleukin-6 (IL-6), platelet activating factor (PAF). The results showed that NXT could significantly decrease the WBV, PV, FIB and prolong the APTT and PT. Meanwhile, NXT significantly decreased the serum contents of MDA, IL-1β, IL-6, ALT, AST and PAF, while elevating T-AOC and SOD levels. These results indicate that NXT could improve coagulation function, enhance antioxidant capacity and suppress inflammation, which might partly account for its mechanisms of action in preventing and treating cardiovascular diseases.

Context Naoxintong Capsule (NXT), a Chinese medicine, has been widely used for the treatment of coronary heart disease (CHD) in clinics. Objective This study evaluated the cardioprotective effects of NXT alone and in combination with ticagrelor (TIC) and atorvastatin (ATO). Materials and methods Qi deficiency and blood stasis rats were established by 8 weeks high fat diet feeding and 16 days exhaustive swimming and randomly divided into seven groups, that is, NXT (250, 500 and 1000 mg/kg/d), TIC (20 mg/kg/d), ATO (8 mg/kg/d), NXT (500 mg/kg/d)+TIC (20 mg/kg/d) and NXT (500 mg/kg/d)+ATO (8 mg/kg/d) group, with oral administration for 12 weeks. The contents of TC, TG, LDL-C, HDL-C, IL-1β, IL-6, IL-8, TNF-α, AST, ALT, SOD, MDA, CK-MB, LDH, TXA2, PGI2, IgA, IgG, IgM and C3 in serum were measured. Results NXT + TIC group was significantly superior to the TIC group in decreasing the levels of TC (4.34 vs. 5.54), TG (3.37 vs. 4.66), LDL-C (1.21 vs. 1.35), LDH (4919.71vs. 5367.19) and elevating SOD level (248.54 vs. 192.04). NXT + ATO group was significantly superior to the ATO group in decreasing the levels of AST (195.931 vs. 241.63), ALT (71.26 vs. 83.16), LDH (4690.05 vs. 5285.82), TXA2 (133.73 vs. 158.67), IgG (8.08 vs. 9.80), C3 (2.03 vs. 2.35) and elevating the levels of HDL-C (1.19 vs. 0.91), SOD (241.91vs. 209.49). Conclusions The present findings demonstrate that the combined use of NXT with TIC and ATO had better integrated regulating effects than TIC and ATO, respectively. The mechanism of action requires further research.

Moyamoya-like vasculopathy, the “puff of smoke”-like small vessels in the brain, is initially identified in patients with Moyamoya disease (MMD), a rare cerebrovascular disease, and later found in patients with various types of neurological conditions, including Down syndrome, Stroke, and vascular dementia. It is thus of interest to understand how this vasculopathy is developed. Here, we provided evidence for cortical astrocytic neogenin (NEO1) deficiency to be a risk factor for its development. NEO1, a member of deleted in colorectal cancer (DCC) family netrin receptors, was reduced in brain samples of patients with MMD. Astrocytic Neo1-loss resulted in an increase of small blood vessels (BVs) selectively in the cortex. These BVs were dysfunctional, with leaky blood-brain barrier (BBB), thin arteries, and accelerated hyperplasia in veins and capillaries, resembled to the features of moyamoya-like vasculopathy. Additionally, we found that both MMD patient and Neo1 mutant mice exhibited altered gene expression in their cortex in proteins critical for not only angiogenesis [e.g., an increase in vascular endothelial growth factor (VEGFa)], but also axon guidance (e.g., netrin family proteins) and inflammation. In aggregates, these results suggest a critical role of astrocytic NEO1-loss in the development of Moyamoya-like vasculopathy, providing a mouse model for investigating mechanisms of Moyamoya-like vasculopathy.

Objective This study was performed to explore the characteristics and outcomes of patients with sepsis accompanied by active cancer who were admitted to the intensive care unit (ICU). Methods The baseline characteristics, infection profiles, and outcomes of patients with sepsis were retrospectively analyzed according to the presence of concomitant active cancer. The association between concomitant active cancer and 28-day mortality was explored. Results Of 23,956 patients with sepsis, 1574 (6.6%) had concomitant active cancer. The most common type was digestive (30.7%). The 28-day mortality ranged from 41.9% to 81.5%. Patients with active cancer had a significantly higher Simplified Acute Physiology Score II and significantly shorter length of ICU stay. Respiratory (32.9%), genitourinary (31.0%), and bloodstream (17.0%) infections were most common. Escherichia coli was the most frequent gram-negative pathogenic bacteria. The 28-day mortality rate was significantly higher in patients with than without active cancer. Concomitant active cancer was associated with increased 28-day mortality in patients with sepsis. Hematological malignancy was associated with a significantly higher risk of death than solid tumors. Conclusions Concomitant active cancer was associated with higher 28-day mortality in patients with sepsis requiring ICU admission. Hematological malignancy was associated with a higher risk of death than solid tumors.

Objective Hyperbaric oxygen (HBO) is an emerging complementary alternative medical approach in glioma treatment. However, its mode of action is unknown, so this was investigated in the present study. Methods We constructed an intracranial glioma model of congenic C57BL/6J mice. Glioma growth under HBO stimulation was assessed by bioluminescent imaging and magnetic resonance imaging. Flow cytometry assessed direct effects of HBO on reactive oxygen species (ROS) signaling of transplanted glioma cells and organs, and quantified mature T cells and subgroups in tumors, the brain, and blood. Results HBO promoted the growth of transplanted GL261-Luc glioma in the intracranial glioma mouse model. ROS signaling of glioma cells and brain cells was significantly downregulated under HBO stimulation, but thymus ROS levels were significantly upregulated. CD3+ T cells were significantly downregulated, while both Ti/Th cells (CD3+CD4+) and Ts/Tc cells (CD3+CD8+) were inhibited in tumors of the HBO group. The percentage of regulatory T cells in Ti/Th (CD3+CD4+) cells was elevated in the tumors and thymuses of the HBO group. Conclusion HBO induced ROS signaling in the thymus, inhibited CD3+ T cell generation, and facilitated malignant glioma cell growth in vivo in the intracranial glioma mouse model.

The observation of the bright pulses and dark square pulses in a graphene-oxide saturable absorber (GOSA) passively mode-locked ytterbium-doped fiber laser has been investigated experimentally. Bright pulses are achieved at a pump power of ~ 200 mW. However, the dark-square-pulse generation starts at a much higher pump power of ~ 450 mW. At the maximum pump power of 600 mW, the dark-square-pulse bunches and harmonic mode locking (HML) can be also obtained by tuning the polarization controller (PC) to different orientations. It is the first demonstration of the bunches and HML of dark square pulses in a GOSA passively mode-locked ytterbium-doped fiber laser with large normal dispersion cavity.

We demonstrate a compact wavelength-tunable and -switchable mode-locked Yb-doped fiber (YDF) laser based on single-walled carbon nanotube (SWCNT) wall paper absorber. Two mechanisms coexist in the fiber cavity. The switchable mode-locked state can be obtained between two wavelengths depending on the fiber-loop-induced cavity birefringence. Because of the intensity-dependent transmission distribution, the proposed fiber laser can be operated in the tunable wavelength mode-locked state from 1025 to 1037 nm. The spectral bandwidth varied from 1.1 to 2.4 nm depending on the operating wavelength and the pump power with pulse duration of hundreds of picoseconds. The average wavelength spacing is 3.6 nm, which can be changed, corresponding to the birefringence of the fiber cavity. Moreover, stable wavelength-tunable mode locking is obtained at room temperature.

Although much is known about the operation of signalized intersections, little or no empirical research has been conducted regarding bicycle capacity at these locations and the correspondent contributory factors. The purpose of this study is to accurately quantify the capacity of bikeway at signalized intersection through a fluid dispersion approach, and ultimately the lane group capacity. Using this total dispersion of bicycle flow, a relationship is also described between bicycle volume per hour and per unit width, signal parameters (length of signal cycle and green time), bicycle flow (arrival rate, density, moving velocity) and geometric intersection distance. Through the videotaping of four intersections that have significant bicycle traffic around Xiaozhai in Xi’an, China, it is ascertained that bicycle capacity varies linearly (but limited by an asymptote domain) associated with the adjustment of these parameters. The analytical results indicate that the impact saturation flow of lane groups containing right-turning vehicles and pedestrian flow at signalized intersections on bicycles is being underestimated. If this is the case, then capacity is being overestimated through the HCM 2000 capacity model and JJ37-90 approach and intersections are not being adequately designed, due to the neglect of conflict nature of mixed traffic arrivals in competing for space.

This study was performed to investigate the correlation between CT perfusion with acetazolamide challenge and angiogenesis in C6 gliomas.Thirty-two male Sprague-Dawley rats were evaluated. The rats were divided randomly to four groups: eight rats with orthotopically implanted C6 gliomas at 10-days old (Group A), eight rats with gliomas at 14-days old (Group B), eight rats with gliomas at 18-days old (Group C), eight rats with orthotopically injected normal saline served as controls. CT perfusion was performed before and after administration of acetazolamide. Changes in perfusion parameters due to acetazolamide administration were calculated and analyzed.Elevated carbon dioxide partial pressure and decreased pH were found in all 32 rats post acetazolamide challenge (P

Many studies focused on the analysis of effect factors contributing to the crashes and development of crash prediction models have resulted in aggregate researches to quantify the safety effects of geometric and traffic variables and environmental concerns on the expected outcome of fatal, injury and/or property damage losses at specific locations. Crash insight regarding different locations, however, has rarely been performed. Such investigations are useful for at least two reasons. First, there is a priori need to identify high risk sites with respect to crash. Second, it is generally believed that different crash types (e.g. rear-end, angle etc.) are associated with road geometry, the environment and traffic condition, and as a result justifying the inside causes of such crashes helps with understanding and improving the specific ability to make effective countermeasures. Therefore, the objectives of this paper are to (1) demonstrate that different crash types are associated to intersections in different ways and (2) reveal that the statistics of intersection crashes may lead to greater insights considering crash occurrence and countermeasure effectiveness. This paper first divides crashes into 5 categories or types: pedestrian-involved, rear-end, head-on, angle and sideswipe crash types. Based on 3208 crashes collected on the intersections in the city of Harbin during the period of 1992–2008, distribution, overall count and the occurrence of rate features are estimated resulting in two models. The performed analysis reveals that safety improvement factors such as the presence of a signal light set, a traffic monitoring device and ITS measure have a positive association with intersection crash in different ways, suggesting that different traffic control and management aspects may be helpful in identifying specific countermeasures in the overall safety improvement project. Santrauka Daugelis tyrimų, nagrinėjančių efektyvumo veiksnius, padedančius nustatyti susidūrimų prognozavimo modelius, paskatino įvairius tyrimus įvertinti eismo aplinkos sudedamųjų dalių ir jų parametrų įtaką mirties ir (arba) turtinės žalos atvejams konkrečiose vietose. Iki šiol tai buvo retas reiškinys. Tokie tyrimai yra svarbūs bent jau dėl dviejų priežasčių. Pirma, reikia nustatyti padidintos rizikos vietas atsižvelgiant į eismo įvykį. Antra, manoma, kad skirtingos susidūrimo rūšys yra susijusios su kelio geometrija, aplinkos ir eismo sąlygomis ir kaip pasekmė, pateisinanti vidines tokių susidūrimų priežastis, padeda suprasti ir pagerinti konkrečias galimybes imtis atsakomųjų veiksmų. Todėl šio darbo tikslas—parodyti, kad skirtingos susidūrimo rūšys įvairiai susijusios su eismu sankryžose, kad susidūrimų sankryžose statistika gali lemti didesnę įžvalgą, atsižvelgiant į įvykusį eismo įvykį ir atsakomųjų priemonių veiksmingumą. Šiame darbe susidūrimai skirstomi į 5 rūšis: susidūrimai su pėsčiaisiais, įvažiavimas į galinę transporto priemonės dalį, susidūrimas priekinėmis transporto priemonės dalimis, kampinis smūgis ir šoninis smūgis. Pasiskirstymas, bendras skaičius ir susidūrimų dažnis apskaičiuojami pagal du modelius remiantis informacija, surinkta iš 3028 eismo įvykių, įvykusių 1992–2008 m. Charbino miesto (Kinija) sankryžose. Atlikta analizė parodė, kad saugaus gerinimo veiksniai, t. y. šviesoforas, eismo stebėjimo prietaisai ir t.t., turi teigiamą įtaką. Skirtingi eismo kontrolės ir valdymo aspektai gali padėti rasti konkrečias atsakomąsias priemones, įgyvendinant visą saugaus eismo gerinimo projektą. Резюме Проблема безопасности дорожного движения актуальна во всех городах мира. Не является исключением и китайский город Харбин. Авторы исследуют влияние совокупности факторов, возникающих до и после дорожно-транспортного происшествия, для оценки эффективности проекта по безопасному движению на перекрестках в упомянутом городе. Исследуются места увеличенного риска возникновения дорожно-транспортного происшествия. Также принимается во внимание, что различные типы дорожно-транспортных происшествий тесно связаны с геометрическими параметрами дороги, условиями окружающей среды, условиями самого движения и т. д. Целью исследования было показать связь и влияние различных типов дорожно-транспортных происшествий на конкретные ситуации движения на перекрестках. Это необходимо для того, чтобы понять необходимость ответных мер по обеспечению безопасности дорожного движения в потенциально опасных местах. Все дорожно-транспортные происшествия разделены на 5 типов. Далее на основании информации о 3028 дорожно-транспортных происшествий, зарегистрированных в период с 1992 по 2008 гг. на перекрестках города Харбина, представлены статистические результаты исследования. Проведенное исследование показало, что меры по увеличению безопасности дорожного движения (например, светофор, видео наблюдение за движением и т. д.) имели положительное влияние. Различные аспекты контроля за дорожным движением и управления им помогают найти ответные меры по претворению в жизнь проекта по обеспечению безопасности дорожного движения. Reikšminiai žodžiai: susidūrimas, sankryža, susidūrimų dažnis, eismo kontrolė, šviesos signalas, atsakomosios priemonės, saugus eismas Ключевые слова: дорожно-транспортное происшествие, безопасность дорожного движения, перекресток, столкновение, контроль за движением, ответные меры

A passively mode-locked Nd:YLF laser with an output-coupling LT-[In.sub.0.25][Ga.sub.0.75]As absorber grown by metal-organic chemical-vapor deposition technique is demonstrated. The continuous-wave mode-locking average output power of 530 mW is obtained at the incident pump power of 10 W corresponding to the peak power of 1.8 kW and pulse energy of 5.4 nJ.