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BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a common, often fatal complication of transcatheter mitral valve replacement (TMVR). Laceration of the anterior mitral leaflet to prevent outflow obstruction (LAMPOON) was safe and effective at preventing LVOT obstruction at 30 days in the National Heart, Lung, and Blood Institute LAMPOON trial. OBJECTIVES: The authors report the 5-year trial outcomes. METHODS: The National Heart, Lung, and Blood Institute LAMPOON trial was a prospective, multicenter, single-arm safety and feasibility study of LAMPOON and transseptal SAPIEN 3 TMVR in annuloplasty rings (valve-in-ring) or native mitral annular calcification (MAC) (valve-in-MAC). All subjects had high predicted risk for LVOT obstruction. Subjects were not excluded for excessive frailty or comorbidity. The primary endpoints were technical success and safety at 30 days. Secondary clinical and echocardiographic endpoints were assessed at 1 year and clinical follow-up at 5 years. RESULTS: Thirty subjects were enrolled between June 2017 and June 2018, equally between the valve-in-MAC and valve-in-ring arms. At 30 days, LAMPOON was successful in all 30 subjects, with no strokes, 1 (3%) death, and 1 (3%) moderate LVOT obstruction. Eighteen (65%) survived to 1 year, and 7 (25%) survived to 5 years. Six (20%) were hospitalized for heart failure in the first year. From baseline to 1 year, there was a 24-point improvement in Kansas City Cardiomyopathy Questionnaire score and a 60-m improvement in 6-minute walk distance. There was no significant change in N-terminal pro-brain natriuretic peptide. At 1 year, LVOT gradients remained low. CONCLUSIONS: LAMPOON enabled TMVR despite the risk for LVOT obstruction. There were no long-term complications associated with LAMPOON. The selection of inoperable patients limited assessment of long-term survival following TMVR. (NHLBI DIR LAMPOON Study: Intentional Laceration of the Anterior Mitral Leaflet to Prevent Left Ventricular Outflow Tract Obstruction During Transcatheter Mitral Valve Implantation; NCT03015194).

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BACKGROUND: Although the survival of patients with transfusion-dependent thalassemia (TD-TM) is reportedly inferior after haploidentical transplantation, the heterogeneity of transplantation approaches in studies suggests the need to assess the effect of one given conditioning regimen on matched and haploidentical transplantation outcomes. OBJECTIVE: A novel PTCy-based approach for patients with TD-TM undergoing haploidentical HSCT was reported in our prior study. We aimed to retrospectively evaluate the real-world efficacy and safety of GvHD prophylaxis in patients with TD-TM after HSCT from matched donors and haploidentical donors (HIDs). STUDY DESIGN: This was a retrospective multicenter study. Of 238 patients with TD-TM who underwent HSCT, 160 underwent peripheral blood HSCT, using uniform GvHD prophylaxis with PTCy, methotrexate, and cyclosporine, at member centers of the Bone Marrow Failure Working Group of Hunan Province between 2019 and 2023. RESULTS: The median age of the cohort was 6 years (95% confidence interval [CI], 6-7 years) at transplantation. Of 160 donors, 99 (61.9%) were haploidentical family members, and the others were matched donors (13 matched siblings, 48 matched or mismatched unrelated donors). The engraftment rate was 98.8% (95% CI: 96.1%-97.7%). HSCT from HIDs had a lower risk of mixed chimerism (HR 0·078, p=0.022). Within 100 days after transplantation, 31 patients (19.6%, 95% CI: 14.0%-26.3%) had grade II-IV acute GvHD, 9 of whom had grade III-IV acute GvHD (5.7%, 95% CI: 2.9%-10.1%). HIDs were significantly associated with a higher risk of grade II-IV acute GvHD (HR 3.973, p = 0.009). Nineteen patients (11.9%, 95% CI: 7.6%-17.6%) developed late acute GvHD after a median of 516 days (95% CI: 407-709 days). Twenty-six patients (16.5%, 95% CI: 11.3%-22.8%) exhibited any one of the diagnostic, distinctive, or atypical features of chronic GvHD according to the 2014 NIH criteria after a median of 690 days (95% CI: 496-902 days). Among these, 7 had NIH-defined chronic GvHD, 14 had only one distinctive sign with no histological evidence, and 5 had only atypical chronic GvHD signs. Of the 26 patients, 5 were classified as having overlap syndrome. Of 21 patients who were classified as having NIH-defined and potential chronic GvHD, 3 had moderate chronic GvHD, whereas 1 had severe chronic GvHD. Logistic regression analyses identified that grade II-IV acute GvHD independently predicted subsequent chronic GVHD (HR 3.920, p=0.006). The rates of chronic GvHD were similar between the matched and HID groups. Thalassemia-free survival (TFS) and event-free survival (EFS) were 97.5% (95% CI: 94.2%-99.2%) and 90.6% (95% CI: 85.4%-94.4%), respectively, after a median of 690 days (95% CI: 496-902 days). TFS rates were similar between the matched and HID groups (p = 0.549). The EFS rate was significantly higher in the matched group than in the HID group (p = 0.033). CONCLUSIONS: Our study suggests that when PTCy-based uniform GVHD prophylaxis is administered, HSCT from matched donors and HIDs results in a low incidence of severe GVHD and treatment-related mortality with satisfactory survival.

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This case report details the clinical course of a 16-year-old female student with Mycoplasma pneumoniae infection complicated by autoimmune encephalitis, spanning from 6 February 2022, to 12 April 2022, with a one-year follow-up. The patient presented with a two-week history of cough and fever, followed by altered consciousness and neuropsychiatric symptoms, including hyperactivity and incoherent speech. Despite normal brain MRI findings, cerebrospinal fluid (CSF) analysis confirmed Mycoplasma pneumoniae with titers of, and positive IgLON5 antibodies. Initial treatment included azithromycin, ceftriaxone, and acyclovir, followed by mechanical ventilation and ECMO due to respiratory failure. The antibiotic regimen was switched to intravenous omadacycline based on genetic testing results. Autoimmune encephalitis was managed with intravenous methylprednisolone, intravenous immunoglobulin (IVIG), and plasma exchange. The patient's condition improved, and she was discharged on 12 March 2022, with normal cognitive and behavioral functions. However, she was readmitted one month later due to cognitive decline and sleep disturbances, with a Mini-Mental State Examination (MMSE) score of 20/30 and a modified Rankin Scale (mRS) score of 3. At the one-year follow-up, her MMSE score had improved to 28/30, and her mRS score was 1. This case underscores the importance of comprehensive diagnostic approaches and personalized treatment strategies in managing complex cases of mycoplasma-related infections and associated autoimmune conditions.

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Objective To investigate the status and influencing factors of pressuring feeding style among caregivers in remote rural areas of Sichuan province. Methods Multistage sampling was conducted to select infants of 6-11 months old who had received complementary food and their caregivers in remote rural areas of Sichuan province.A questionnaire was used to collect sociodemographic characteristics of infants and their caregivers,pressuring feeding behaviors,feeding environment,and caregivers' negative emotions.Quantile regression was employed to analyze the factors influencing pressuring feeding among caregivers of infants. Results A total of 1358 pairs of infants and their caregivers were included,with the pressuring feeding behavior score of 11 (8,14).Parity was the protective factor for caregivers' pressuring feeding (ß25=-1.17,P<0.001;ß50=-1.40,P=0.002;ß75=-2.18,P<0.001).Whether infants played with toys while eating (ß25=1.00,P<0.001;ß50=1.20,P=0.003;ß75=1.42,P<0.001) and whether infants watched TV/mobile phones (ß25=0.50,P=0.048;ß50=1.07,P=0.004) were the risk factors.At the 75th percentile,caregivers' negative emotions were the risk factor for pressuring feeding (ß75=0.94,P=0.015).Caregivers' education background (ß25=0.83,P=0.034;ß50=0.87,P=0.021) and family income (ß75=1.09,P=0.012) were also significantly associated with pressuring feeding scores at different quartile points. Conclusion Pressuring feeding behaviors of caregivers in remote rural areas of Sichuan province need to be improved.Based on the characteristics of infants and their families,guidance should be carried out to improve the feeding environment and the mental health of caregivers,thereby promoting reasonable feeding behaviors among caregivers of infants in rural areas.

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Objective To investigate the current status of physical activity and depressive symptoms among middle-aged and older adults in Chengdu,Sichuan and explore the relationship between physical activity and depressive symptoms. Methods Multi-stage proportional stratified random sampling was employed to select middle-aged and older adults aged ≥45 years as the participants,and face-to-face interviews were carried out to collect data.Logistic regression was adopted to explore the relationship between physical activity and depressive symptoms in middle-aged and older adults.The trend test was performed for the relationship between different levels of physical activity and depressive symptoms.The subgroup analysis and the test for multiplicative interactions were conducted for the relationship between physical activity and depressive symptoms. Results A total of 4376 middle-aged and older adults were included.Among them,14.58% (638/4376),25.98% (1137/4376),and 27.83% (1218/4376) had depressive symptoms,failed to reach the guideline-recommended standards of physical activity,and were at low levels of physical activity,respectively.There was a negative association between reaching guideline-recommended physical activity standard and depressive symptoms in middle-aged and older adults (OR=0.713,95%CI=0.589-0.861,P<0.001).In addition,moderate levels (OR=0.714,95%CI=0.586-0.871,P=0.001) and high levels of physical activity (OR=0.705,95%CI=0.548-0.906,P=0.006) had negative associations with the presence of depressive symptoms.The trend test revealed that the negative association between physical activity and depressive symptoms in middle-aged and older adults enhanced as the level of physical activity increased (Pfor trend=0.001).The subgroup analysis and the test for multiplicative interactions revealed that neither reaching guideline-recommended physical activity standards or not nor the physical activity level had an interaction with each of the subgroups (all Pfor interaction>0.05). Conclusion The current status of depressive symptoms among middle-aged and older adults in Chengdu,Sichuan needs to be ameliorated.A negative association existed between reaching the guideline-recommended physical activity standard and presence of depressive symptoms,and the negative association enhanced as the physical activity level elevated.

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Objective: Hepatoblastoma (HB) is the most commonly seen pediatric liver malignancy. The preliminary experiment of our research group found that cyclin dependent kinase 1 (CDK1) was upregulated in HB. By in silico analysis, long noncoding RNA (lncRNA) HAND2 antisense RNA 1 (HAND2-AS1) was determined as the research object. Herein, HAND2-AS1 expression in HB and its effect and mechanism on HB were extensively investigated. Methods: CDK1-related lncRNAs were searched using the microarray data from the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA) online database. qRT-PCR, Western blot, and immunohistochemistry were performed to determine the mRNA expression and protein levels of target genes. MTT, flow cytometry and DAPI staining assays were conducted to measure proliferation activity, cell cycle progression, and apoptosis of HB cells. The interaction between lncRNA and protein was determined by RNA pull-down and FISH assays. Luciferase assay was applied to identify whether HAND2-AS1 stimulates the transcription of CDK1. CDK1 mRNA stability was detected through actinomycin D assay. Aycloheximide assay was used to detect the CDK1 protein stability. Results: HAND2-AS1 was downregulated in HB tissues and cells. HAND2-AS1 overexpression impeded HB cells proliferation activity and cycle progression while inducing cell apoptosis of HB cells, while knockdown of HAND2-AS1 emerged the opposite effect. HAND2-AS1 negatively correlated with CDK1. HAND2-AS1 downregulated CDK1 expression by affecting the transcriptional activity, mRNA and protein stability of CDK1. Furthermore, HAND2-AS1 impeded HB cell proliferation and cycle progression while inducing cell apoptosis by downregulating CDK1. Conclusion: Our research highlights that HAND2-AS1 can exert a tumor-suppressive effect on HB through the negative regulation of CDK1, and the HAND2-AS1/CDK1 is expected to be a diagnostic molecular marker and therapeutic target for HB in clinical practice.

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Programmed cell death contributes to neurological damage in ischemic stroke, especially during the reperfusion stage. Several cell death pathways have been tested preclinically and clinically, including ferroptosis, necroptosis, and apoptosis. However, the sequence and complex interplay between cell death pathways during ischemia/reperfusion remains under investigation. Here, we unbiasedly investigated cell death pathways during ischemia/reperfusion by utilizing RNA sequencing analysis and immunoblot assays and revealed that ferroptosis and necroptosis occurred early post-reperfusion, followed by apoptosis. Ferroptosis inhibitor Liproxstatin-1 effectively inhibited necroptosis during reperfusion, while the necroptosis inhibitor Necrostatin-1 suppressed protein expression consistent with ferroptosis activation. Protein-protein interaction analysis and iron chelation therapy by deferoxamine mesylate indicate that iron is capable of promoting both ferroptosis and necroptosis in middle cerebral artery occlusion/repression modeled mice. Treatment of cells with iron led to a disruption in redox balance with activated necroptosis and increased susceptibility to ferroptosis. Collectively, these data uncovered a complex interplay between ferroptosis and necroptosis during ischemic stroke and indicated that multiple programmed cell death pathways may be targeted co-currently.

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The literature shows that maternal stress can influence behavior and immune function in F1. Yet, most studies on these are from the laboratory, and replicated studies on the mechanisms by which maternal stress drives individual characteristics are still not fully understood in wild animals. We manipulated high- and low-density parental population density using large-scale field enclosures and examined behavior and immune traits. Within the field enclosures, we assessed anti-keyhole limpet hemocyanin immunoglobulin G (anti-KLH IgG) level, phytohemagglutinin (PHA) responses, hematology, cytokines, the depressive and anxiety-like behaviors and prevalence and intensity of coccidial infection. We then collected brain tissue from juvenile voles born at high or low density, quantified mRNA and protein expression of corticotropin-releasing hormone (CRH) and glucocorticoid receptor gene (NR3C1) and measured DNA methylation at CpG sites in a region that was highly conserved with the prairie vole CRH and NR3C1 promoter. At high density, we found that the F1 had a lower DNA methylation level of CRH and a higher DNA methylation level of NR3C1, which resulted in an increase in the expression levels of the CRH mRNA and protein expression and further reduced the expression levels of the NR3C1 mRNA and protein expression, and ultimately led to have delayed responses to acute immobilization stress. Juvenile voles born at high density also reduced anti-KLH IgG levels and PHA responses, increased cytokines, and depressive and anxiety-like behaviors, and the effects further led to higher coccidial infection. From the perspective of population density inducing the changes in behavior and immunity at the brain level, our results showed a physiological epigenetic mechanism for population self-regulation in voles. Our results indicate that altering the prenatal intrinsic stress environment can fundamentally impact behavior and immunity by DNA methylation of HPA-axis genes and can further drive population fluctuations in wild animals.

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Excessive exposure to metals in daily life has been proposed as an environmental risk factor for neurological disorders. Oxidative stress is an inevitable stage involved in the neurotoxic effects induced by metals, nevertheless, the underlying mechanisms are still unclear. In this study, we used arsenic as a representative environmental heavy metal to induce neuronal oxidative stress and demonstrated that both in vitro and in vivo exposure to arsenic significantly increased the level of N6-methyladenosine (m6A) by down-regulating its demethylase FTO. Importantly, the results obtained from FTO transgenic mice and FTO overexpressed/knockout cells indicated that FTO likely regulated neuronal oxidative stress by modulating activating transcription factor 3 (ATF3) in a m6A-dependent manner. We also identified the specific m6A reader protein, YTHDC1, which interacted with ATF3 and thereby affecting its regulatory effects on oxidative stress. To further explore potential intervention strategies, cerebral metabolomics was conducted and we newly identified myo-inositol as a metabolite that exhibited potential in protecting against arsenic-induced oxidative stress and cognitive dysfunction. Overall, these findings provide new insights into the importance of the FTO-ATF3 signaling axis in neuronal oxidative stress from an m6A perspective, and highlight a beneficial metabolite that can counteract the oxidative stress induced by arsenic.

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INTRODUCTION: Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. PATIENTS AND METHODS: This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. RESULTS: From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196-2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173-2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). CONCLUSIONS: The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted.

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Atypical porcine pestivirus (APPV) can cause congenital tremor type A-II in neonatal piglets, posing a significant threat to swine herd health globally. Our previous study demonstrated that the Mut domains, comprising 112 amino acids at the N-terminus, are the primary functional regions of the E2 protein of APPV. This study identified 14 host cellular proteins that exhibit potential interactions with the Mut domains of the E2 protein using yeast two-hybrid screening. Using bioinformatics analysis, we discovered that the Mut domains of the E2 protein might exert regulatory effects on apoptosis by modulating energy metabolism within the mitochondria. We also conducted co-immunoprecipitation, glutathione S-transferase pull-down, and immunofluorescence assays to confirm the interaction between the Mut domains of the E2 protein and cathepsin H and signal sequence receptor subunit 4 (SSR4). Ultimately, SSR4 enhanced APPV replication in vitro. In summary, our study successfully elucidated the interactions between the Mut domains of the E2 protein and host cell protein, predicted the potential pathways implicated in these interactions, and demonstrated SSR4 involvement in APPV infection. These significant findings contribute valuable knowledge toward a deeper understanding of APPV pathogenesis and the role of the Mut domains of the E2 protein in this intricate process.

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BACKGROUND: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. METHODS: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. RESULTS: Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p < .05). CONCLUSIONS: Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. PLAIN LANGUAGE SUMMARY: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients.

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Objective: This study aimed to explore the correlation between microbiota dysbiosis and hypothyroidism in early pregnancy by 16S rRNA amplicon sequencing combined with metagenomic sequencing. Methods: Sixty pregnant women (30 with hypothyroidism and 30 normal controls) were recruited for 16S rRNA amplicon sequencing, and 6 patients from each group were randomly selected for metagenomic sequencing to assess the gut microbiome profile. Results: The 16S rRNA results showed that beta-diversity in the hypothyroidism group was decreased. The relative abundances of the Prevotella and Paraprevotella genera increased in the hypothyroidism group, and Blautia predominated in the controls. The metagenomics results revealed that Prevotella_stercorea_CAG_629, Prevotella_hominis, Prevotella_sp_AM34_19LB, etc. were enriched in the hypothyroidism group at the species level. Functional analysis revealed that the pyridoxal 5'-phosphate synthase pdxT subunit module was decreased, and the short-chain fatty acid (SCFA) transporter and phospholipase/carboxylesterase modules were strongly enriched in the hypothyroidism group. Hypothyroidism patients had increased C-reactive protein (CRP), interleukin-2 (IL-2), IL-4, IL-10, and tumor necrosis factor (TNF)-α levels. The pyridoxal 5'-phosphate synthase pdxT subunit, the SCFA transporter, and the phospholipase/carboxylesterase module were associated with different Prevotella species. Conclusion: In early pregnancy, women with hypothyroidism exhibit microbiota dysbiosis, and Prevotella may affect the metabolism of glutamate, SCFA, and phospholipases, which could be involved in the development of hypothyroidism during pregnancy.

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Conductive metal-organic frameworks (c-MOFs) hold promise for highly sensitive sensing systems due to their conductivity and porosity. However, the fabrication of c-MOF thin films with controllable morphology, thickness, and preferential orientation remains a formidable yet ubiquitous challenge. Herein, we propose an innovative template-assisted strategy for constructing MOF-on-MOF (Ni3(HITP)2/NUS-8 (HITP: 2,3,6,7,10,11-hexamino-tri(p-phenylene))) systems with good electrical conductivity, porosity, and solution processability. Leveraging the 2D nature and solution processability of NUS-8, we achieve the controllable self-assembly of Ni3(HITP)2 on NUS-8 nanosheets, producing solution-processable Ni3(HITP)2/NUS-8 nanosheets with a film conductivity of 1.55 × 10-3 S·cm-1 at room temperature. Notably, the excellent solution processability facilitates the fabrication of large-area thin films and printing of intricate patterns with good uniformity, and the Ni3(HITP)2/NUS-8-based system can monitor finger bending. Gas sensors based on Ni3(HITP)2/NUS-8 exhibit high sensitivity (LOD ~ 6 ppb) and selectivity towards ultratrace H2S at room temperature, attributed to the coupling between Ni3(HITP)2 and NUS-8 and the redox reaction with H2S. This approach not only unlocks the potential of stacking different MOF layers in a sequence to generate functionalities that cannot be achieved by a single MOF, but also provides novel avenues for the scalable integration of MOFs in miniaturized devices with salient sensing performance.

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BACKGROUND: There were limited data investigating platelet indices in predicting peritoneal dialysis (PD) outcomes on comorbidities. The aim of this study was to evaluate the association between platelet indices and new-onset comorbidity and all-cause mortality in PD patients. METHODS: A single-center, retrospective observational cohort study was conducted in incident PD patients from 28 December 2011 to 24 January 2018, and followed up until 31 December 2022. Time to the first new-onset cardiovascular disease (CVD) and time to the first new-onset infection event after PD were identified as the primary outcomes. All-cause mortality was identified as the secondary endpoint. The correlation between platelet indices and comorbidities and all-cause mortality were assessed by Cox model. Data of liver disease status was not collected and analyzed. Survival curves were performed by Kaplan-Meier method with log-rank tests. RESULTS: A total of 250 incident PD patients with a median follow-up of 6.79 (inter-quarter range 4.05, 8.89) years was included. A total of 81 and 139 patients experienced the first new-onset CVD and infection event respectively during the follow-up period. High mean platelet volume (MPV) was independently associated with high risk of time to the first new-onset CVD (HR 1.895, 95% CI 1.174-3.058, p = 0.009) and all-cause mortality (HR 1.710, 95% CI 1.155-2.531, p = 0.007). Patients with low mean platelet volume to platelet count ratio (MPV/PC) were prone to occur the new-onset infection events (log rank 5.693, p = 0.017). Low MPV/PC (HR 0.652, 95% CI 0.459-0.924, p = 0.016) was significantly associated with the time to the first new-onset infection event on PD. CONCLUSIONS: Platelet indices were associated with the new-onset CVD, infectious comorbidities and all-cause mortality on PD. Low MPV/PC was associated with time to the first new-onset infection event in PD patients. Moreover, high MPV was associated with new-onset CVD and all-cause mortality in the incident PD patients.

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Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. DEAD/H-box helicase 11 (DDX11), a DNA helicase, has been implicated in the progression of several cancers. Yet, the precise function of DDX11 in OSCC is poorly understood. The DDX11 expression in OSCC cells and normal oral keratinocytes was evaluated in the Gene Expression Omnibus database (GSE146483 and GSE31853). SCC-4 and CAL-27 cells expressing doxycycline-inducible DDX11 or DDX11 shRNA were generated by lentiviral infection. The role of DDX11 in OSCC cells was determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry assay, TUNEL staining, and western blot. The effects of DDX11 on tumor growth were explored in a xenograft nude mouse model. The relationship between DDX11 and transcription factor Yin Yang-1 (YY1) was researched using the dual luciferase report assay and chromatin immunoprecipitation assay. DDX11 expression was significantly upregulated in OSCC cells. Knockdown of DDX11 inhibited cell proliferation, induced cell cycle arrest, and suppressed PI3K-AKT pathway, while DDX11 overexpression showed opposite effects. The number of apoptotic cells was increased in DDX11 silenced cells. DDX11 upregulation or knockdown accelerated or suppressed tumor growth in vivo, respectively. Moreover, the YY1 bound and activated the DDX11 promoter, resulting in increasing DDX11 expression. Forced expression DDX11 reversed the anticancer effects of YY1 silencing on OSCC cells. DDX11 has tumor-promoting function in OSCC and is transcriptionally regulated by YY1, indicating that DDX11 may serve as a potential target for the OSCC treatment.

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Introduction: Noise reduction (NR) algorithms have been integrated into modern digital hearing aids to reduce noise annoyance and enhance speech intelligibility. This study aimed to evaluate the influences of a novel hearing aid NR algorithm on individuals with severe-to-profound hearing loss. Methods: Twenty-five participants with severe-to-profound bilateral sensorineural hearing loss underwent three tests (speech intelligibility, listening effort, and subjective sound quality in noise) to investigate the influences of NR. All three tests were performed under three NR strength levels (Off, Moderate, and Strong) for both speech in noise program (SpiN) and speech in loud noise program (SpiLN), comprising six different hearing aid conditions. Results: NR activation significantly reduced listening effort. Subjective sound quality assessments also exhibited benefits of activated NR in terms of noise suppression, listening comfort, satisfaction, and speech clarity. Discussion: Individuals with severe-to-profound hearing loss still experienced advantages from NR technology in both listening effort measure and subjective sound quality assessments. Importantly, these benefits did not adversely affect speech intelligibility.