Cochlear implantation in patients with Streptococcus suis meningitis: clinical characteristics and postoperative evaluation.

BACKGROUND: Hearing loss is a common sequala of Streptococcus suis (S. suis) meningitis, but few have addressed cochlear implantation (CI) candidates with S. suis meningitis. OBJECTIVES: To assess the clinical characteristics and CI postoperative outcomes in S. suis meningitis patients. MATERIAL AND METHODS: Eight S. suis meningitis patients underwent CI at Sun Yat-sen Memorial Hospital between 2020 and 2023. Control groups included (1) non-Suis meningitis patients (n = 12) and (2) non-meningitis patients (n = 35). Electrode impedances and neural response telemetry (NRT) thresholds were recorded at one month after surgery. The auditory performance-II (CAP) and speech intelligibility rating (SIR) were recorded at the last visit. RESULTS: CAP scores of S. suis meningitis patients were significantly lower than those of non-Suis meningitis and non-meningitis patients (p = .019; p<.001). And NRT thresholds of S. suis meningitis patients were higher than those of non-Suis meningitis and non-meningitis patients (p = .006; p = .027). CONCLUSIONS AND SIGNIFICANCE: It is recommended for S. suis meningitis CI candidates to undergo CI promptly after controlling infection, preferably within four to six weeks. CI users with S. suis meningitis tend to exhibit suboptimal hearing rehabilitation outcomes, possibly associated with the more severe damage on spiral ganglion cells after S. suis meningitis.

Comparative epidemiology of outbreaks caused by SARS-CoV-2 Delta and Omicron variants in China.

From 2020 to December 2022, China implemented strict measures to contain the spread of severe acute respiratory syndrome coronavirus 2. However, despite these efforts, sustained outbreaks of the Omicron variants occurred in 2022. We extracted COVID-19 case numbers from May 2021 to October 2022 to identify outbreaks of the Delta and Omicron variants in all provinces of mainland China. We found that omicron outbreaks were more frequent (4.3 vs. 1.6 outbreaks per month) and longer-lasting (mean duration: 13 vs. 4 weeks per outbreak) than Delta outbreaks, resulting in a total of 865,100 cases, of which 85% were asymptomatic. Despite the average Government Response Index being 12% higher (95% confidence interval (CI): 9%, 15%) in Omicron outbreaks, the average daily effective reproduction number (Rt) was 0.45 higher (95% CI: 0.38, 0.52, p < 0.001) than in Delta outbreaks. Omicron outbreaks were suppressed in 32 days on average (95% CI: 26, 39), which was substantially longer than Delta outbreaks (14 days; 95% CI: 11, 19; p = 0.004). We concluded that control measures effective against Delta could not contain Omicron outbreaks in China. This highlights the need for continuous evaluation of new variants' epidemiology to inform COVID-19 response decisions.

Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia.

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10-2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10-3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10-3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy

Introduction To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. Methods This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland–Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. Results The median of translation error between stages of the AlignRT positioning process was (0.03–0.07) cm, and the median of rotation error was (0.20–0.40)°, which were significantly better than those of the Fraxion positioning process (0.09–0.11) cm and (0.60–0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01 cm, − 0.07 cm, 0.03 cm, − 0.30°, − 0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10 cm and 0.50° (AU)

Analysis of Individualized Silicone Rubber Bolus Using Fan Beam Computed Tomography in Postmastectomy Radiotherapy: A Dosimetric Evaluation and Skin Acute Radiation Dermatitis Survey.

Objective: To investigate the dosimetric effects of using individualized silicone rubber (SR) bolus on the target area and organs at risk (OARs) during postmastectomy radiotherapy (PMRT), as well as evaluate skin acute radiation dermatitis (ARD). Methods: A retrospective study was performed on 30 patients with breast cancer. Each patient was prepared with an individualized SR bolus of 3 mm thickness. Fan-beam computed tomography (FBCT) was performed at the first and second fractions, and then once a week for a total of 5 times. Dosimetric metrics such as homogeneity index (HI), conformity index (CI), skin dose (SD), and OARs including the heart, lungs, and spinal cord were compared between the original plan and the FBCTs. The acute side effects were recorded. Results: In targets' dosimetric metrics, there were no significant differences in Dmean and V105% between planning computed tomography (CT) and actual treatments (P > .05), while the differences in D95%, V95%, HI, and CI were statistically significant (P < .05). In OARs, there were no significant differences between the Dmean, V5, and V20 of the affected lung, V5 of the heart and Dmax of the spinal cord (P > .05) except the V30 of affected lung, which was slightly lower than the planning CT (P < .05). In SD, both Dmax and Dmean in actual treatments were increased than plan A, and the difference was statistically significant (P < .05), while the skin-V20 and skin-V30 has no difference. Among the 30 patients, only one patient had no skin ARD, and 5 patients developed ARD of grade 2, while the remaining 24 patients were grade 1. Conclusion: The OR bolus showed good anastomoses and high interfraction reproducibility with the chest wall, and did not cause deformation during irradiation. It ensured accurate dose delivery of the target and OARs during the treatment, which may increase SD by over 101%. In this study, no cases of grade 3 skin ARD were observed. However, the potential of using OR bolus to reduce grade 1 and 2 skin ARD warrants further investigation with a larger sample size.

Efficacy and safety of the Valsalva maneuver in relieving venipuncture pain in children and adults: A systematic review and meta-analysis.

Venipuncture is a common invasive clinical procedure, and pain management during puncture has been of interest to healthcare professionals. The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of the Valsalva maneuver (VM) for the relief of venipuncture pain in children and adults. PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP database, and CBM were searched from inception to December 2023 for all available randomized controlled trials (RCTs) that evaluated the impact of VM on venipuncture. Two reviewers independently performed study selection, data extraction, and risk of bias assessment. Continuous variables were analyzed by mean differences (MD) or standardized mean differences (SMD), whereas dichotomous variables were analyzed by risk ratios (RR). A total of 22 studies involving 1740 participants were included. The pooled results showed that VM relieved pain intensity during venipuncture in children (SMD = -0.89, 95% CI = -1.47 to -0.30, p = 0.003) and adults (SMD = -1.11, 95% CI = -1.46 to -0.77, p < 0.00001), reduced anxiety intensity (SMD = -1.07, 95% CI = -1.68 to -0.47, p = 0.0005), and shortened puncture time (MD = -13.52, 95% CI = -21.14 to -5.90, p = 0.0005). There was no significant difference in the success rate of venous cannulation, MAP, HR, or incidence of adverse events in subjects who performed VM compared to controls. VM was an effective and safe method of pain management that reduced pain intensity during venipuncture in children and adults without significant adverse effects. The results of this meta-analysis need to be further validated by more rigorous and larger RCTs.

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma.

BACKGROUND: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. METHODS: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. RESULTS: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. CONCLUSIONS: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy.

INTRODUCTION: To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. METHODS: This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland-Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. RESULTS: The median of translation error between stages of the AlignRT positioning process was (0.03-0.07) cm, and the median of rotation error was (0.20-0.40)°, which were significantly better than those of the Fraxion positioning process (0.09-0.11) cm and (0.60-0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01 cm, - 0.07 cm, 0.03 cm, - 0.30°, - 0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10 cm and 0.50°. CONCLUSIONS: The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment.

The weight-adjusted-waist index and cognitive impairment among U.S. older adults: a population-based study.

Objectives: Multiple research projects have provided evidence of the correlation between obesity and cognitive impairment. WWI, a novel metric for assessing obesity, has the potential to provide a more precise assessment of muscle and fat mass. This research aimed to investigate the association between WWI and cognitive functioning among elderly individuals residing in the United States. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2014. Weighted multiple linear regression models, smoothed fitted curves, and generalized weighted models were employed to examine the associations between WWI and cognitive function in linear and nonlinear contexts. Results: The study included a cohort of 2,764 adult volunteers aged 60 years and older, all with complete data. Upon controlling for all potential confounding variables, our analysis revealed statistically significant negative associations between WWI and the Digit Symbol Substitution Test (DSST) score. Specifically, for each 1-unit increase in WWI, there was a corresponding loss of 3.57 points in the DSST score [-3.57 (-4.31, -2.82)]. The negative correlations between WWI with CERAD total word recall [-0.63 (-0.85, -0.40)], CERAD delayed recall [-0.19 (-0.30, -0.07)], and AFT [-0.65 (-0.94, -0.37)] were significant only in partially adjusted models. Conclusion: Higher WWI was associated with poorer cognitive function.

A solution and practice for combining multi-source heterogeneous data to construct enterprise knowledge graph.

The knowledge graph is one of the essential infrastructures of artificial intelligence. It is a challenge for knowledge engineering to construct a high-quality domain knowledge graph for multi-source heterogeneous data. We propose a complete process framework for constructing a knowledge graph that combines structured data and unstructured data, which includes data processing, information extraction, knowledge fusion, data storage, and update strategies, aiming to improve the quality of the knowledge graph and extend its life cycle. Specifically, we take the construction process of an enterprise knowledge graph as an example and integrate enterprise register information, litigation-related information, and enterprise announcement information to enrich the enterprise knowledge graph. For the unstructured text, we improve existing model to extract triples and the F1-score of our model reached 72.77%. The number of nodes and edges in our constructed enterprise knowledge graph reaches 1,430,000 and 3,170,000, respectively. Furthermore, for each type of multi-source heterogeneous data, we apply corresponding methods and strategies for information extraction and data storage and carry out a detailed comparative analysis of graph databases. From the perspective of practical use, the informative enterprise knowledge graph and its timely update can serve many actual business needs. Our proposed enterprise knowledge graph has been deployed in HuaRong RongTong (Beijing) Technology Co., Ltd. and is used by the staff as a powerful tool for corporate due diligence. The key features are reported and analyzed in the case study. Overall, this paper provides an easy-to-follow solution and practice for domain knowledge graph construction, as well as demonstrating its application in corporate due diligence.

A study on the transmission dynamics of COVID-19 considering the impact of asymptomatic infection.

The COVID-19 epidemic has been spreading around the world for nearly three years, and asymptomatic infections have exacerbated the spread of the epidemic. To analyse and evaluate the role of asymptomatic infections in the spread of the epidemic, we establish an improved COVID-19 infectious disease dynamics model. We fit the epidemic data in the four time periods corresponding to the selected 614G, Alpha, Delta and Omicron variants and obtain the proportion of asymptomatic persons among the infected persons gradually increased and with the increase of the detection ratio, the cumulative number of cases has dropped significantly, but the decline in the proportion of asymptomatic infections is not obvious. Therefore, in view of the hidden transmission of asymptomatic infections, the cooperation between various epidemic prevention and control policies is required to effectively curb the spread of the epidemic.

The need for a clinical case definition in test-negative design studies estimating vaccine effectiveness.

Test negative studies have been used extensively for the estimation of COVID-19 vaccine effectiveness (VE). Such studies are able to estimate VE against medically-attended illness under certain assumptions. Selection bias may be present if the probability of participation is associated with vaccination or COVID-19, but this can be mitigated through use of a clinical case definition to screen patients for eligibility, which increases the likelihood that cases and non-cases come from the same source population. We examined the extent to which this type of bias could harm COVID-19 VE through systematic review and simulation. A systematic review of test-negative studies was re-analysed to identify studies ignoring the need for clinical criteria. Studies using a clinical case definition had a lower pooled VE estimate compared with studies that did not. Simulations varied the probability of selection by case and vaccination status. Positive bias away from the null (i.e., inflated VE consistent with the systematic review) was observed when there was a higher proportion of healthy, vaccinated non-cases, which may occur if a dataset contains many results from asymptomatic screening in settings where vaccination coverage is high. We provide an html tool for researchers to explore site-specific sources of selection bias in their own studies. We recommend all groups consider the potential for selection bias in their vaccine effectiveness studies, particularly when using administrative data.

A pathway analysis of the impact of childhood domestic violence on depression in middle-aged and elderly people from the perspective of life course.

BACKGROUND: Negative life events in early life have a cumulative effect on health trajectory changes in middle and old age, and some scholars have used life course theory as a guide to empirically explore the effect of childhood adversity or adverse experiences on depression in the elderly, but few study focuses on violence within the family. OBJECTIVE: To explore the influence mechanism of domestic violence experience on depression in later life in middle-aged and elderly people, and to provide academic support for the whole society to pay attention to good family function and intergenerational interaction, and to propose whole-life health promotion strategies. PARTICIPANTS AND SETTING: This paper selects the 2014 life course survey data and 2018 cross-sectional data of the China Health and Elderly Care Longitudinal Survey for analysis, and the research objects are middle-aged and elderly people aged 45 and above. METHODS: Based on a retrospective survey of 3008 middle-aged and elderly people, this study analyzed the influence path of domestic violence on depression level in childhood by using multiple mediation models, and used the Bootstrap method to test the significance of indirect effects. RESULTS: Based on controlling for gender, age, age square, household registration, marital status, community environment and education level, childhood domestic violence had a direct positive effect on depression level in the elderly (P < 0.001), and childhood domestic violence also had an indirect effect on the depression level of the elderly through childhood health status, income logarithm and IADL (P < 0.05). CONCLUSION: As a life experience in early life, childhood domestic violence has a cumulative effect on depression in middle-aged and elderly people, is an important risk factor for depression, and has an important impact on mental health in later life.

Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma

Objective Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy of the gastrointestinal tract for which therapeutic options are scarce. This study screens for LOXL2, a key gene in ESCC, and explains the molecular mechanism by which it promotes the progression of ESCC. Methods Immunohistochemical staining was performed to detect the expression level of LOXL2 in ESCC tissues and paraneoplastic tissues. CCK-8 and Transwell assays were performed to assess the effects of LOXL2 knockdown and overexpression on the proliferation, apoptosis, migration and invasion ability of ESCC cells. High-throughput sequencing analysis screens for molecular mechanisms of action by which LOXL2 promotes ESCC progression. Western blotting and qRT-PCR were used to determine the expression levels of relevant markers. Results LOXL2 is positively expressed in ESCC and highly correlated with poor prognosis. Silencing LOXL2 significantly inhibited the proliferation, migration and invasive ability of ESCC cells, whereas overexpression showed the opposite phenotype. High-throughput sequencing suggested that LOXL2-associated differentially expressed genes were highly enriched in the PI3K/AKT signaling pathway. In vitro cellular assays confirmed that silencing LOXL2 significantly reduced PI3K, p-AKTThr308 and p-AKTSer473 gene and protein expression levels, while overexpression increased all three gene and protein levels, while AKT gene and protein expression levels were not significantly different. Conclusion This study found that LOXL2 may regulate the PI3K/AKT signaling pathway and exert protumor effects on ESCC cells through phosphorylation of AKT. LOXL2 may be a key clinical warning biomarker or therapeutic target for ESCC (AU)

Effects of School-Based Preventive Measures on COVID-19 Incidence, Hong Kong, 2022.

We show that school closures reduced COVID-19 incidence rates in children by 31%-46% in Hong Kong in 2022. After school reopening accompanied by mask mandates, daily rapid testing, and vaccination requirements, school-reported cases correlated with community incidence rates. Safe school reopening is possible when appropriate preventive measures are used.

Catalytic supercritical water oxidation of o-chloroaniline over Ru/rGO: Reaction variables, conversion pathways and nitrogen distribution.

To ascertain the reaction variables on o-chloroaniline (o-ClA) mineralization, total nitrogen (TN) removal rate, and N-species distribution, o-ClA was subjected to catalytic supercritical water oxidation (CSCWO) in a fused quartz tube reactor (FQTR). The findings demonstrated that when the temperature, reaction time, and excess oxidant were 400 °C, 90 min, and 150%, respectively, the mineralization rate of o-ClA could reach more than 95%. Moreover, potential degradation pathways of o-ClA in supercritical water oxidation (SCWO) was proposed according to the GC-MS results. TN removal rate is significantly impacted by Ru/rGO, despite the fact that its catalytic effect on the mineralization of o-ClA was not particularly noteworthy. Compared with no catalyst, the TN removal rate of o-ClA obviously increased from 44.1% to 90.3% at 400 °C, 10 wt% Ru loading, 90 min and 200% excess oxidant. In addition, N-species distribution in SCWO and CSCWO were also investigated. Results indicated that the Ru/rGO catalyst could accelerate the oxidation of ammonia-N and convert it to nitrate-N, promoting N2 generation. Finally, the possible N transformation pathway in CSCWO of o-ClA was proposed. As a result, this work offers fundamental information about o-ClA catalytic oxidation removal in the SCWO process.

Revisiting assumptions in test-negative studies for estimating vaccine effectiveness: the need for a clinical case definition.

Test negative studies have been used extensively for the estimation of COVID-19 vaccine effectiveness (VE). Such studies are able to estimate VE against medically-attended illness under certain assumptions. Selection bias may be present if the probability of participation is associated with vaccination or COVID-19, but this can be mitigated through use of a clinical case definition to screen patients for eligibility, which increases the likelihood that cases and non-cases come from the same source population. We examined the extent to which this type of bias could harm COVID-19 VE through systematic review and simulation. A systematic review of test-negative studies was re-analysed to identify studies ignoring the need for clinical criteria. Studies using a clinical case definition had a lower pooled VE estimate compared with studies that did not. Simulations varied the probability of selection by case and vaccination status. Positive bias away from the null (i.e., inflated VE consistent with the systematic review) was observed when there was a higher proportion of healthy, vaccinated non-cases, which may occur if a dataset contains many results from asymptomatic screening in settings where vaccination coverage is high. We provide an html tool for researchers to explore site-specific sources of selection bias in their own studies. We recommend all group consider the potential for selection bias in their vaccine effectiveness studies, particularly when using administrative data.

Tracing back of relapse clones by Ig/TCR gene rearrangements reveals complex patterns of recurrence in pediatric acute lymphoblastic leukemia.

INTRODUCTION: Relapse remained the major obstacle to improving the prognosis of children with acute lymphoblastic leukemia (ALL). This study aimed to investigate the changing patterns of Ig/TCR gene rearrangements between diagnosis and relapse and the clinical relevance and to explore the mechanism of leukemic relapse. METHODS: Clonal Ig/TCR gene rearrangements were screened by multiplex PCR amplification in 85 paired diagnostic and relapse bone marrow (BM) samples from children with ALL. The new rearrangements presented at relapse were quantitatively assessed by the RQ-PCR approach targeting the patient-specific junctional region sequence in 19 diagnostic samples. The relapse clones were further back-traced to diagnostic and follow-up BM samples from 12 patients. RESULTS: Comparison of Ig/TCR gene rearrangements between diagnosis and relapse showed that 40 (57.1%) B-ALL and 5 (33.3%) T-ALL patients exhibited a change from diagnosis to relapse, and 25 (35.7%) B-ALL patients acquired new rearrangements at relapse. The new relapse rearrangements were present in 15 of the 19 (78.9%) diagnostic samples as shown by RQ-PCR, with a median level of 5.26 × 10-2 . The levels of minor rearrangements correlated with B immunophenotype, WBC counts, age at diagnosis, and recurrence time. Furthermore, back-tracing rearrangements in 12 patients identified three patterns of relapse clone dynamics, which suggested the recurrence mechanisms not only through clonal selection of pre-existing subclones but also through an ongoing clonal evolution during remission and relapse. CONCLUSION: Backtracking Ig/TCR gene rearrangements in relapse clones of pediatric ALL revealed complex patterns of clonal selection and evolution for leukemic relapse.

Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway.

BACKGROUND: Mesenchymal stem cell (MSC) transplantation is a promising therapeutic approach for noise-induced hearing loss (NIHL). As the indispensable role of apoptosis in MSC transplantation was raised, the benefits of MSC-derived apoptotic vesicles (apoVs) in several disease models have been proved. However, whether apoVs benefit in NIHL have not been studied yet. METHODS: Female CBA/J mice and HEI-OC1 cells were used in this study. Flow cytometry, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were used to characterize apoVs. Proteomic analysis was used to identify function proteins in apoVs. Immunofluorescence was used to reveal distribution pattern. Auditory brainstem response (ABR) test was used to measure the effect of apoVs treatment. DCFH-DA staining and MitoSOX staining were used to indicate oxidative damage. Western-blot and qRT-PCR were used to study the signaling pathways. RESULTS: We found that apoVs can be endocytosed by hair cells through systemic administration. Importantly, apoVs administration effectively attenuated NIHL and reduced hair cell loss by resisting oxidative damage in vivo. Further, apoVs application activated forkhead box o3 (FOXO3a)-mitochondrial superoxide dismutase 2(SOD2) pathway, which may relate to signal transduction and activators of transcription 3 (STAT3) in apoVs. CONCLUSIONS: These findings uncovered the role of apoVs in preventing NIHL and resisting oxidative damage, indicating that apoVs is a promising way for inner ear delivery and a prospective cell-free therapy for NIHL.

Size-dependent effect of microplastics on toxicity and fate of diclofenac in two algae.

Microplastics (MPs) are frequently detected in natural waters and usually acted as vectors for other pollutants, leading to possible threats to aquatic organisms. This study investigated the impact of polystyrene MPs (PS MPs) with different diameters on two algae Phaeodactylum tricornutum and Euglena sp., and the combined toxicity of PS MPs and diclofenac (DCF) in two algae was also studied. Significant inhibition of P. tricornutum was observed after 1 d exposure of 0.03 µm MPs at 1 mg L-1, whereas the decreased growth rate of Euglena sp. was recovered after 2 d exposure. However, their toxicity decreased in the presence of MPs with larger diameters. The oxidative stress contributed a major for the size-dependent toxicity of PS MPs in P. tricornutum, while in Euglena sp. the toxicity was mainly caused by a combination of oxidative damage and hetero-aggregation. Also, PS MPs alleviated the toxicity of DCF in P. tricornutum and the DCF toxicity continually decreased as their diameter increased, whereas the DCF at environmentally concentration could weaken the toxicity of MPs in Euglena sp. Moreover, the Euglena sp. revealed a higher removal for DCF, especially in the presence of MPs, but the higher accumulation and bioaccumulation factors (BCFs) indicated a possible ecological risk in natural waters. The present study explored discrepancy on the size-dependent toxicity and removal of MPs associated with DCF in two algae, providing valuable data for risk assessment and pollution control of MPs associated with DCF.