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BackgroundChildhood and adolescent cancer represent a significant health burden in the United States. Current and precise epidemiological data are crucial to develop effective cancer control plans and ultimately reduce the burden of childhood and adolescent cancer.MethodsWe analyzed data obtained from cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Age-standardized incidence and death rates, assessed using joinpoint analysis, were quantified as annual percentage changes (APC) and average percentage changes (AAPC).ResultsThe overall cancer incidence rate in 2008–2018 was 187.9 per 1,000,000 persons. Cancer incidence rates demonstrated a sustained upward trend, with an APC of 0.8 from 1975 to 2018. Incidence rates during 2008–2018 remained stable among non-Hispanic Black children but increased among other racial and ethnic groups. Leukemias, central nervous system tumors, and lymphomas were the most common cancer groups for patients aged 0–19 years. Cancer death rates decreased among children [AAPC, −1.3 (95% CI, −1.5 to −1.1)] during 2009–2019, while were stable among adolescents during that period.ConclusionsIn this study, we analyzed cancer incidence and mortality rates and trends in children aged 0–19 years in the United States. Our findings revealed an overall increase in cancer incidence rates among children and adolescents, accompanied by a decline in cancer mortality rates over time. These rates and trends varied by age, sex, and particularly race and ethnicity, highlighting the significance of comprehending and addressing disparities and ultimately reducing the disease burden of childhood and adolescent cancer.

Recently, herpesvirus of turkeys (HVT), which was initially employed as a vaccine against Marek’s disease (MD), has been shown to be a highly effective viral vector for producing recombinant vaccines that can simultaneously express the protective antigens of multiple poultry diseases. Prior to the development of commercial HVT-vectored dual-insert vaccines, the majority of HVT-vectored vaccines in use only contained a single foreign gene and were often generated using time-consuming and inefficient traditional recombination methods. The development of multivalent HVT-vectored vaccines that induce simultaneous protection against several avian diseases is of great value. In particular, efficacy interference between individual recombinant HVT vaccines can be avoided. Herein, we demonstrated the use of CRISPR/Cas9 gene editing technology for the insertion of an IBDV (G2d) VP2 expression cassette into the UL45/46 region of the recombinant rHVT-HA viral genome to generate the dual insert rHVT-VP2-HA recombinant vaccine. The efficacy of this recombinant virus was also evaluated in specific pathogen-free (SPF) chickens. PCR and sequencing results showed that the recombinant virus rHVT-VP2-HA was successfully constructed. Vaccination with rHVT-VP2-HA produced high levels of specific antibodies against IBDV (G2d) and H9N2/Y280. rHVT-VP2-HA can provide 100% protection against challenges with IBDV (G2d) and H9N2/Y280. These results demonstrate that rHVT-VP2-HA is a safe and highly efficacious vaccine for the simultaneous control of IBDV (G2d) and H9N2/Y280.

BackgroundHead and neck squamous cell carcinoma (HNSCC), an extremely aggressive tumor, is often associated with poor outcomes. The standard anatomy-based tumor–node–metastasis staging system does not satisfy the requirements for screening treatment-sensitive patients. Thus, an ideal biomarker leading to precise screening and treatment of HNSCC is urgently needed.MethodsTen machine learning algorithms—Lasso, Ridge, stepwise Cox, CoxBoost, elastic network (Enet), partial least squares regression for Cox (plsRcox), random survival forest (RSF), generalized boosted regression modelling (GBM), supervised principal components (SuperPC), and survival support vector machine (survival-SVM)—as well as 85 algorithm combinations were applied to construct and identify a consensus immune-derived gene signature (CIDGS).ResultsBased on the expression profiles of three cohorts comprising 719 patients with HNSCC, we identified 236 consensus prognostic genes, which were then filtered into a CIDGS, using the 10 machine learning algorithms and 85 algorithm combinations. The results of a study involving a training cohort, two testing cohorts, and a meta-cohort consistently demonstrated that CIDGS was capable of accurately predicting prognoses for HNSCC. Incorporation of several core clinical features and 51 previously reported signatures, enhanced the predictive capacity of the CIDGS to a level which was markedly superior to that of other signatures. Notably, patients with low CIDGS displayed fewer genomic alterations and higher immune cell infiltrate levels, as well as increased sensitivity to immunotherapy and other therapeutic agents, in addition to receiving better prognoses. The survival times of HNSCC patients with high CIDGS, in particular, were shorter. Moreover, CIDGS enabled accurate stratification of the response to immunotherapy and prognoses for bladder cancer. Niclosamide and ruxolitinib showed potential as therapeutic agents in HNSCC patients with high CIDGS.ConclusionCIDGS may be used for stratifying risks as well as for predicting the outcome of patients with HNSCC in a clinical setting.

The effectiveness of COVID-19 vaccines wanes over time and the emergence of the SARS-CoV-2 Omicron variant led to the accelerated expansion of efforts for booster vaccination. However, the effect and contribution of booster vaccination with inactivated COVID-19 vaccines remain to be evaluated. We conducted a retrospective close contacts cohort study to analyze the epidemiological characteristics and Omicron infection risk, and to evaluate the effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection, symptomatic COVID-19, and COVID-19 pneumonia during the outbreaks of Omicron BA.2 infection from 1 February to 31 July 2022 in Guangdong, China. A total of 46,547 close contacts were identified while 6.3% contracted Omicron BA.2 infection, 1.8% were asymptomatic infection, 4.1% developed mild COVID-19, and 0.3% had COVID-19 pneumonia. We found that females and individuals aged 0-17 or ≥ 60 years old were more prone to SARS-CoV-2 infection. The vaccinated individuals showed lower infection risk when compared with the unvaccinated people. The effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 was 28.6% (95% CI: 11.6%, 35.0%) and 39.6% (95% CI: 30.0, 47.9) among adults aged ≥ 18 years old, respectively when compared with full vaccination. Booster vaccination provided a moderate level of protection against SARS-CoV-2 infection (VE: 49.9%, 95% CI: 22.3%-67.7%) and symptomatic COVID-19 (VE: 62.6%, 95% CI: 36.2%-78.0%) among adults aged ≥ 60 years old. Moreover, the effectiveness of booster vaccination was 52.2% (95% CI: 21.3%, 70.9%) and 83.8% (95% CI: 28.1%, 96.3%) against COVID-19 pneumonia in adults aged ≥ 18 and ≥ 60 years old, respectively. The reduction of absolute risk rate of COVID-19 pneumonia in the booster vaccination group was 0·96% (95% CI: 0.33%, 1.11%), and the number needed to vaccinate to prevent one case of COVID-19 pneumonia was 104 (95% CI: 91, 303) in adults aged ≥ 60 years old. In summary, booster vaccination with inactivated COVID-19 vaccines provides a low level of protection against infection and symptomatic in adults of 18-59 years old, and a moderate level of protection in older adults of more than 60 years old, but a high level of protection against COVID-19 pneumonia in older adults.

A self-powered IoT system with high integration, robust performance, and adaptability to complex environments is one of the current research hotspots. Piezoelectric materials have been widely used in pressure sensing and energy harvesting due to their stable output electrical properties. In this paper, a heterogeneous integrated self-powered IoT system based on a lithium niobate (LiNbO3) piezoelectric device and CMOS readout circuit is proposed. The piezoelectric sensor is fabricated by depositing electrodes on the surface of the 36°Y-cut LiNbO3 piezoelectric material. The sensitivity of the fabricated sensor is 17.5 mV/kPa. Based on the CSMC 0.18 μm BCD process, a ring voltage-controlled oscillator (VCO) based on the current starvation delay element is designed as a wireless data transmission unit. The oscillator has two tuning terminals, which can realize frequency alignment and voltage threshold judgment. Using photolithography, wire bonding technology, etc., the heterogeneous integration of the Si-based chip and LiNbO3 piezoelectric device is realized. The experimental results show that below 1.8 V supply voltage, the oscillation frequency of the chip increases with the increase in the control terminal voltage, which provides an idea for solving the energy supply problem of an IoT system. This system has great application potential in the field of self-powered sensing.

PurposePrevious studies on monocular blindness (MB) have mainly focused on concept and impact. The present study measured spontaneous brain activity in MB patients using the percentage of amplitude fluctuation (PerAF) method.MethodsTwenty-nine patients with MB (21 male and 8 female) and 29 age-, gender-, and weight-matched healthy controls (HCs) were recruited. All participants underwent resting state functional magnetic resonance imaging (rs-fMRI). The PerAF method was used to analyze the data and evaluate the spontaneous regional brain activity. The ability of PerAF values to distinguish patients with MB from HCs was analyzed using receiver operating characteristic (ROC) curves, and correlation analysis was used to assess the relationship between PerAF values of brain regions and the Hospital Anxiety and Depression Scale (HADS) scores.ResultsPerAF values in Occipital_Mid_L/Occipital_Mid_R/Cingulum_ Mid_L were significantly lower in patients with MB than in controls. Conversely, values in the Frontal_Sup_Orb_L/Frontal_Inf_Orb_L/Temporal _Inf_L/Frontal_Inf_Oper_L were significantly higher in MB patients than in HCs. And the AUC of ROC curves were follows: 0.904, (p < 0.0001; 95%CI: 0.830–0.978) for Frontal_Sup_Orb_L/Frontal_Inf_Orb_L; Temporal_Inf_L 0.883, (p < 0.0001; 95% CI: 0.794–0.972); Frontal_Inf_Oper_L 0.964, (p < 0.0001; 95% CI: 0.924–1.000), and 0.893 (p < 0.0001; 95% CI: 0.812–0.973) for Occipital_Mid_L; Occipital_Mid_R 0.887, (p < 0.0001; 95% CI: 0.802–0.971); Cingulum_Mid_L 0.855, (p < 0.0001; 95% CI: 0.750–0.960).ConclusionThe results of our study show abnormal activity in some brain regions in patients with MB, indicating that these patients may be at risk of disorder related to these brain regions. These results may reflect the neuropathological mechanisms of MB and facilitate early MB diagnoses.

Purpose: In this study, we analyzed the differences between hypertension patients with ocular metastasis of liver cancer and those with metastases to other sites, the correlation between history of HBV and liver cancer metastasis, and independent risk factors for ocular metastasis.Methods: We used treatment records from 488 patients with metastases of primary liver cancer from August 2001 to May 2015, divided into two groups based on metastatic sites: OM (ocular metastasis) and NOM (non-ocular, other sites of metastasis) groups. The Student’s t-test and Chi-square test were used to assess the significance of differences between the groups and define the relationship between history of HBV and ocular metastasis of liver cancer. Binary logistic regression analysis was used to identify indicators of ocular metastasis of liver cancer and receiver operating curve (ROC) analyses to estimate their diagnostic value.Results: No significant differences in sex, age, tumor stage, pathological type, or treatment were identified between the OM and NOM groups, while the prevalence of HBV was higher in the former than that in latter. Binary logistic regression demonstrated that AFP and CA-125 were independent indicators of liver metastasis (both p < 0.001). ROC curve analyses generated cut-off values for AFP and CA-125 of 957.2 ng/ml and 114.25 U/ml, respectively, with corresponding AUC values of 0.739 and 0.810. The specificity of the combination of AFP and CA-125 was higher than either factor separately.Discussion: To explore the diagnostic value of AFP and CA125 in predicting the development of ocular metastases of hypertensive patients with liver cancer, which will help us to diagnose the occurrence and development of the disease more accurately and make the best clinical diagnosis and treatment measures.

Objective: Lung cancer is a common malignant tumor characterized by challenging detection and lack of specificity in clinical manifestations. To investigate the correlation of tumor markers in the serum with liver metastasis and prognosis of lung cancer.Methods: A total of 3,046 elderly lung cancer patients were retrospectively studied between September 1999 and July 2020. Divided into liver metastasis group and non-liver metastasis group. We compared a series of serum biomarkers between the two groups of elderly patients to predict the prognosis in patients with lung cancer by fluorescence in situ hybridization (FISH), advanced flow cytometry (FCM) and multi tumor marker protein chip, including tumor markers in the serum included alkaline phosphatase (ALP), serum calcium, hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin fragment 19 (Cyfra21-1), carbohydrate antigen-125 (CA-125), carbohydrate antigen-153 (CA-153), carbohydrate antigen-199 (CA-199), and free prostate specific antigen (free PSA). We used binary logistic regression analysis to determine risk factors, and used receiver operating curve (ROC) analysis to evaluate the diagnostic value of liver metastases in elderly patients with lung cancer.Results: The proportion of lung cancer in the liver metastasis group was higher than that observed in the non-liver metastases group. The expression levels of CA-125, Cyfra21-1, and NSE in the liver metastasis group of lung cancer were significantly higher than those reported in the non-liver metastases group (p < 0.05). ROC curve analysis shows that the area under the curve of CA-125, Cyfra21-1, and NSE are 0.614, 0.616 and 0.608, respectively. The sensitivity and specificity of CA-125 were 45.70% and 76.20%, the sensitivity and specificity of Cyfra21-1 were 60.10% and 57.10%, and the sensitivity and specificity of NSE were 44.10% and 75.00%, respectively.Conclusion: High levels of CA-125, Cyfra21-1, and NSE in the serum may be associated with liver metastasis in elderly patients with lung cancer. CA-125 and NSE are factors influencing the prognosis of elderly patients with liver metastasis of lung cancer.

Objective: Lung cancer is a common malignant tumor, characterized by being difficult to detect and lacking specific clinical manifestations. This study aimed to find out the risk factors of mediastinal lymph node metastasis and explore the correlation between serum tumor markers and mediastinal lymph node metastasis and lung cancer prognosis.Methods: A retrospective study of 3,042 lung cancer patients (330 patients with mediastinal lymph node metastasis and 2,712 patients without mediastinal lymph node metastasis) collected from the First Affiliated Hospital of Nanchang University from April 1999 to July 2020. The patients were divided into two groups, namely, mediastinal lymph node metastasis group and non-mediastinal lymph node metastasis group. Student’s t test, non-parametric rank sum test and chi-square test were used to describe whether there is a significant difference between the two groups. We compared the serum biomarkers of the two groups of patients, including exploring serum alkaline phosphatase (ALP), calcium hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA-199, CA -153, cytokeratin fragment 19 (CYFRA 21-1), total prostate specific antigen (TPSA), neuron-specific enolase (NSE) levels and the incidence and prognosis of lung cancer mediastinal lymph node metastasis. Binary logistic regression analysis was used to determine its risk factors, and receiver operating curve (ROC) analysis was used to evaluate its diagnostic value for mediastinal lymph node metastasis.Results: Binary logistic regression analysis showed that carcinoembryonic antigen and CYFRA 21-1 were independent risk factors for mediastinal lymph node metastasis in patients with lung cancer (p < 0.001 and p = 0.002, respectively). The sensitivity and specificity of CEA for the diagnosis of mediastinal lymph node metastasis were 90.2 and 7.6%, respectively; CYFRA 21-1 were 0.6 and 99.0%, respectively.Conclusion: Serum CEA and CYFRA 21-1 have predictive value in the diagnosis of mediastinal lymph node metastasis in patients with lung cancer.

With the prevalence of the Internet and new media channels, consumer reviews have become one of the main determinants of Consumers’ purchasing decisions. This paper uses the Latent Dirichlet Allocation (LDA) model to identify the key factors that are of major concern to consumers, including design factors, laptop setup factors, logistics factors, after-sales factors, and user experience factors. And, we classify these factors into product quality factors and supporting service factors for new products. We then explore the relationship between online reviews and purchase decisions under these different factors, and also further explore the impact of interactions between online review metrics on purchase decisions. Our findings suggest that the impact of online reviews on consumer purchase decisions also varies considerably across different consumer focus factors. In addition, we find that the impact of the interaction between online review features is complex. In particular, consumers do not follow the positive guidance and make purchase decisions as we would expect when confronted with a large number of positive emotional polarity online reviews. Meanwhile, the interaction between negative emotional polarity and variance of online reviews had no significant effect on consumer purchase decisions. The variance of online reviews has a limited role in reducing consumer risk perceptions triggered by negative emotional polarity. Our study provides new evidence for the study of the impact of online reviews through text mining.

ObjectiveTo investigate voxel-based morphometry (VBM) by using magnetic resonance imaging (MRI) in meibomian gland dysfunction patients with severe obesity (PATs) and to explore the application of VBM in the early diagnosis, prevention of cognitive impairment and targeted treatment of this disease.MethodsSixteen PATs and 12 healthy controls (HCs) were enrolled and underwent MRI. Whole-head images were analyzed using VBM and data were compared between groups using an independent samples t-test. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic value of this approach. Mini-mental state examination (MMSE) scores were used to assess cognitive impairment and were analyzed using an independent samples t-test.ResultsCompared with HCs, the VBM values in PATs were reduced in the left cerebellum and right thalamus but increased in the right brainstem, right precuneus and right paracentral lobule. The results of ROC curve analysis indicated that VBM may be useful in meibomian gland disease diagnosis. Comparison of MMSE scores between groups showed mild cognitive impairment in PATs.ConclusionPATs showed altered VBM values in some brain areas. These findings may provide information about the pathophysiology of meibomian gland dysfunction and may help to explain the underlying mechanisms of clinical manifestations in PATs, such as cognitive impairment. Abnormal VBM values in these brain areas may serve as predictive factors for development of meibomian gland disease in severely obese people and as indicators for individualized treatment.

BackgroundTo date, no in-depth study has been conducted on the intrinsic pathological relationship between altered brain activity and related behavioral changes in patients with orbital fracture (OF).PurposeThe present research aimed to explore the potential functional network cerebrum activities in patients with OF using resting state functional magnetic resonance imaging–fractional amplitude of low-frequency fluctuation (rsfMRI-fALFF). This technique can reveal dynamic functional changes in specific cerebrum areas.MethodsTwenty patients with OF and 20 healthy controls (HCs) were included, closely matched in terms of gender, age, weight, and education level. To record spontaneous cerebral activity changes, the rsfMRI-fALFF tool was applied. Receiver operating characteristic (ROC) curves and Pearson's correlation analysis were used to analyze mean fALFF values in specific cerebrum regions and to explore changes of behavioral changes in patients with OF. The Hospital Depression and Anxiety scale was applied to reveal the relationship between emotional states and fALFF values of the right superior temporal gyrus in patients with OF.ResultsIn comparison with HCs, significantly lower fALFF values were detected in the left anterior cingulate gyrus (LACG) and right superior temporal gyrus (RSTG) in patients with OF. ROC curve analysis showed excellent accuracy. The mean fALFF values of the RSTG negatively correlated with the depression score as well as the anxiety score.ConclusionThe finding of abnormal spontaneous activities in cerebral regions may contribute to more comprehensive understanding of the potential neural network changes in patients with OF. The changes of fALFF value in patients with OF may help to gauge their emotional changes and clinical recovery levels.

ObjectiveThe percent amplitude of fluctuation (PerAF) technique was utilized to evaluate the neural functions of specific cerebrum areas in patients with toothache (TA).Patients and MethodsAn aggregation of 18 patients with TA (eight males and 10 females) were included in the study. We also recruited 18 healthy controls (HCs; eight men and 10 women) aligned for sex and age. Resting functional magnetic resonance imaging (rs-fMRI) scans were obtained. Then, we utilized the PerAF method and a support vector machine (SVM) to analyze the image data and measure neural abnormalities in related cerebrum areas. Receiver operating characteristic (ROC) curve analysis was utilized to appraise the two data sets.ResultsThe PerAF signals in the right dorsolateral superior frontal gyrus (RDSFG) and the right posterior central gyrus (RPCG) of TA sufferers were lower than HC signals. These results may reveal neural dysfunctions in relevant cerebrum regions. The AUC values of PerAF in the two areas were 0.979 in the RDSFG and 0.979 in the RPCG. The SVM results suggested that PerAF could be utilized to distinguish the TA group from HCs with a sensitivity of 75.00%, a specificity of 66.67%, and an accuracy of 70.83%.ConclusionPatients with TA had marked differences in PerAF values in some regions of the cerebrum. Changes in PerAF values represented distinctions in blood oxygen level dependent semaphore intensity, which reflected the overactivity or inactivation of some cerebrum areas in those suffering from TA. At the same time, we analyzed the PerAF values of TAs with ROC curve, which can be helpful for the diagnosis of TA severity and subsequent treatment. Our results may help to elucidate the pathological mechanism of TA.

Global climate change has increased the frequency of extreme climate events, and their effects on the nutritional quality, especially on amino acids in rice, have not been quantified. The data from a 3-year low temperature stress (LTS) experiment including two rice varieties (Huaidao 5 and Nanjing 46), seven minimum/maximum temperature levels (one optimal 21/27°C and six LTS levels from 17/23 to 6/12°C), and three LTS durations (3, 6, and 9 days) after flowering, revealed significant interactive effects of LTS at different stages, durations, and temperature levels on the content and accumulation of amino acids. LTS increased rice total amino acid content, while decreasing its accumulation, with higher sensitivities to LTS at the flowering stage than at the grain filling stage. In most treatments, the lysine (the first limiting amino acid) and phenylalanine content were increased under LTS at early and peak flowering stages but decreased at the grain filling stage in both varieties, and only leucine content was increased at all three stages after flowering, while the content of other essential amino acids differed among the two varieties. With an increase of 1°C·d per day in the accumulated cold degree days, the relative content of the essential amino acids was increased by 0.01–0.41%, depending on the rice variety and growth stage. Our results suggest that LTS can improve nutritional quality of amino acids of rice grains in terms of amino acids content, especially at flowering stage. These results provide critical insights for assessing the potential impact of extreme climates on the nutrient quality of rice under future climate change.

ObjectiveUtilizing the fractional amplitude of low-frequency fluctuations (fALFF) technique, this study sought to correlate spontaneous cerebral abnormalities with the clinical manifestations of meibomian gland dysfunction (MGD) in severely obese (SO) population.Subjects and MethodsTwelve MGD patients in SO population (PATs) (4 males and 8 females) and twelve healthy controls (HCs) (6 males and 6 females) matched by gender and age were enrolled. Every participant underwent resting-state functional magnetic resonance imaging (rs-MRI) scanning. Spontaneous cerebral activity alterations were examined using the fALFF method. Receiver operating characteristic (ROC) curves were utilized to classify the medial fALFF values of the PATs and HCs. PATs were also asked to complete anxiety and depression score forms, permitting a correlation analysis.ResultsIn contrast with HCs, PATs had prominently increased fALFF values in the left lingual gyrus, the right globus pallidus, the right anterior cingulate and paracingulate gyri and the left middle occipital lobe (P < 0.05), and decreased fALFF values in the right cerebellum, the left fusiform gyrus, the right medial orbitofrontal gyrus, the left triangle inferior frontal gyrus and the left inferior parietal gyrus (P < 0.05). The results of the ROC curve indicated that changes in regional fALFF values might help diagnose MGD in SO population. Moreover, fALFF values in the right cerebellum of PATs were positively correlated with hospital anxiety and depression scores (HADS) (r = 0.723, P = 0.008). The fALFF values in the left triangle inferior frontal gyrus of PAT were negatively correlated with HADS (r = −0.651, P = 0.022).ConclusionsAberrant spontaneous activity was observed in multiple regions of the cerebrum, offering helpful information about the pathology of MGD in SO population. Aberrant fALFF values in these regions likely relates to the latent pathologic mechanisms of anomalous cerebral activities in PATs.

PurposeTo evaluate potential regional homogeneity (ReHo) cerebrum function lesions in people with severe obesity and meibomian gland dysfunction (SM) and probe the connection between aberrant cerebrum activity and clinical manifestations.Patients and MethodsAn aggregation of 12 patients with SM, and 12 healthy controls (HCs) closely matched in age and gender were enrolled. We applied corneal confocal microscopy and fundus angiography to compare imaging distinctions between the two groups. SMs were required to carefully fill out the Hospital Anxiety Depression Scale (HADS) forms, and a correlation analysis was performed. ReHo was also utilized to appraise partial differences in spontaneous cerebrum function. Receiver operating characteristic (ROC) curves were created to partition ReHo values between patients with SM and the HCs.ResultsReHo values for the left cerebellum (LC), right fusiform gyrus (RFG), left inferior temporal gyrus (LITG), left rectus gyrus (LRG), right thalamus (RT), right caudate (RC), left insula (LI), and left thalamus (LT) of subjects with SM were notably higher than those of the HCs (P < 0.05). ReHo values of the right middle frontal gyrus (RMFG) in subjects with SM were decreased notably compared to the HCs (P < 0.05). ReHo values for the RMFG showed a negative correlation with the anxiety scores (ASs; r = −0.961, P < 0.001) and ReHo values for the RFG showed a positive correlation with the depression scores (DSs; r = 0.676, P = 0.016). The areas under the ROC curve were 1.000 (P < 0.001) for the RMFG, LC, LITG, LRG, RC, LI, and LT and 0.993 (P < 0.001) for the RFG and RT. The results from the ROC curve analysis indicated that changes in the ReHo values of some brain regions may help diagnose SM.ConclusionOur research emphasized that patients with SM had lesions in synchronized neural activity in many encephalic areas. Our discoveries may provide beneficial information for exploring the neuromechanics of SM.

We aim to investigate potential morphological alterations of the brain in female climacteric patients with dry eye (DE) and their relationship to behavioral performances. Twenty-five female patients with DE disease during the female climacteric period and 25 age and education-matched healthy controls (HCs) underwent magnetic resonance imaging. Imaging data were analyzed using voxel-based morphometry (VBM) to identify group differences in DE patients and HCs. Compared with HCs, patients with DE during the female climacteric period had significantly decreased VBM in the Putamen_L, Thalamus_R, Precuneus_L, Frontal_Sup_R, Cingulum_Mid_L, and Frontal_Mid_L. There was increased VBM in the Temporal_Pole_Sup_R, Precentral_R and Insula_L. Receiver operating characteristic curve analysis indicated that the VBM method has clear potential for diagnosis of DE patients during the climacteric period. Correlation analysis found a negative correlation between the VBM values of the Putamen_L and the anxiety score (AS) and depression score (DS), a positive correlation was found between VBM values of the Temporal_Pole_Sup_R and AS. Moreover, VBM values in the Cingulum_Mid_L were positively correlated with AS and DS. These results revealed abnormal spontaneous activity in the brain regions of patients with DE during the climacteric period, which may indicate underlying pathological mechanisms. These results may help to advance clinical treatments.

ObjectiveTo analyze the potential changes in brain neural networks in resting state functional magnetic resonance imaging (rs-fMRI) scans by regional homogeneity (ReHo) in patients with mild cognitive impairment (MCI).MethodsWe recruited and selected 24 volunteers, including 12 patients (6 men and 6 women) with MCI and 12 healthy controls matched by age, sex, and lifestyle. All subjects were examined with rs-fMRI to evaluate changes in neural network connectivity, and the data were analyzed by ReHo method. Correlation analysis was used to investigate the relationship between ReHo values and clinical features in different brain regions of MCI patients. The severity of MCI was determined by the Mini-Mental State Examination (MMSE) scale.ResultsThe signals of the right cerebellum areas 4 and 5, left superior temporal, right superior temporal, left fusiform, and left orbital middle frontal gyri in the patient group were significantly higher than those in the normal group (P < 0.01 by t-test of paired samples). The signal intensity of the right inferior temporal and left inferior temporal gyri was significantly lower than that of the normal group (P < 0.01). The ReHO value for the left inferior temporal gyrus correlated negatively with disease duration, and the value for the right inferior temporal gyrus correlated positively with MMSE scores.ConclusionMild cognitive impairment in patients with pre- Alzheimer’s disease may be related to the excitation and inhibition of neural networks in these regions. This may have a certain guiding significance for clinical diagnosis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations and the pathogenesis of SLE is still unclear. Various omics results have been reported for SLE, but the molecular hallmarks of SLE, especially in patients with different disease activity, using an integrated multi-omics approach have not been fully investigated. Here, we collected blood samples from 10 healthy controls (HCs) and 40 SLE patients with different clinical activity including inactive (IA), low activity (LA), and high activity (HA). Using an integrative analysis of proteomic, metabolomic and lipidomic profiles, we report the multi-omics landscape for SLE. The molecular changes suggest that both the complement system and the inflammatory response were activated in SLEs and were associated with disease activity. Additionally, activation of the immunoglobulin mediated immune response were observed in the LA stage of the disease, however this immune response was suppressed slightly in the HA stage. Finally, an imbalance in lipid metabolism, especially in sphingolipid metabolism, accompanied with dysregulated apolipoproteins were observed to contribute to the disease activity of SLE. The multi-omics data presented in this study and the characterization of peripheral blood from SLE patients may thus help provide important clues regarding the pathogenesis of SLE.

BackgroundKIF15 plays a vital role in many biological processes and has been reported to influence the occurrence and development of certain human cancers. However, there are few systematic evaluations on the role of KIF15 in human cancers, and the role of KIF15 in the diagnosis and prognosis of nasopharyngeal carcinoma (NPC) also remains unexplored. Therefore, this study aimed to conduct a pan-cancer analysis of KIF15 and evaluate its diagnostic and prognostic potential in NPC.MethodsThe expression pattern, prognostic value, molecular function, tumor mutation burden, microsatellite instability, and immune cell infiltration of KIF15 were examined based on public databases. Next, the diagnostic value of KIF15 in NPC was analyzed using the Gene Expression Omnibus (GEO) database and immunohistochemistry (IHC). Kaplan–Meier curves, Cox regression analyses, and nomograms were used to evaluate the effects of KIF15 expression on NPC prognosis. Finally, the effect of KIF15 on NPC was explored by in vitro experiments.ResultsThe expression of KIF15 was significantly upregulated in 20 out of 33 cancer types compared to adjacent normal tissue. Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analysis showed that KIF15 could participate in several cancer-related pathways. The increased expression level of KIF15 was correlated with worse clinical outcomes in many types of human cancers. Additionally, KIF15 expression was related to cancer infiltration of immune cells, tumor mutation burden, and microsatellite instability. In the analysis of NPC, KIF15 was significantly upregulated based on the GEO database and immunohistochemistry. A high expression of KIF15 was negatively associated with the prognosis of patients with NPC. A nomogram model integrating clinical characteristics and KIF15 expression was established, and it showed good predictive ability with an area under the curve value of 0.73. KIF15 knockdown significantly inhibited NPC cell proliferation and migration.ConclusionsOur findings revealed the important and functional role of KIF15 as an oncogene in pan-cancer. Moreover, high expression of KIF15 was found in NPC tissues, and was correlated with poor prognosis in NPC. KIF15 may serve as a potential therapeutic target in NPC treatment.

PurposeThis study aimed to explore factors associated with recurrence and metastasis after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and provide evidence for NPC treatment.MethodsWe retrospectively analysed the treatment dose and survival outcomes of 645 patients with nasopharyngeal carcinoma without distant metastases treated with IMRT for the first time at three treatment centres in the Guangxi Zhuang Autonomous Region, China, between January 2009 and December 2012.ResultsThere were 9.3% of patients (60/645) had recurrence and 17.5% (113/645) had distant metastasis 5 years after treatment. The 1-year, 3-year and 5-year local recurrence rates were 0.9%, 6.5% and 9.0% respectively. And the 1-year, 3-year and 5-year distant metastasis rates were 3.4%, 10% and 17.2%, respectively. In the 60 patients with recurrence, the in-field, marginal-field, and out-field recurrence rates were 93.3% (56/60), 5.0% (3/60) and 1.7% (1/60), respectively. Recurrence failures occurring within the first three years after treatment accounted for 81.7% (49/60). In the 113 patients with metastasis, the size of the cervical lymph node, the presence of lower cervical lymph node metastasis, the residual cervical lymph node size and the time of residual cervical lymph node complete response (CR) were independent prognostic factors for DMFS (P

Avian reoviruses (ARVs) are ubiquitous in domestic poultry with 80% of them being non-pathogenic and they are frequently found in clinically healthy birds. ARVs have also been known to be the etiological agents of viral arthritis (VA), tenosynovitis, myocarditis, runting-stunting syndrome (RSS), and respiratory and enteric disease in chickens. Significant economic losses during the process of poultry husbandry are due, in part, to unmitigated ARV infections throughout the poultry industry. Recently, many isolates shared genetic similarities between those recovered from wild birds and those recovered from poultry. One explanation may be that there is a degree of spillover and spillback of ARVs between the two groups. However, studies on the role of wild birds in the epidemiology and pathogenicity of ARVs are insufficient. Here, we describe the pathogenicity in specific pathogen-free (SPF) chickens of ARV originating from wild birds. The challenge experiment was conducted in six groups including a negative control group, a positive control group (reference strain of S1133), and four groups (A15-157, A18-13, A18-205, A19-106) infected with ARVs from wild birds. The 7-day-old SPF chickens were inoculated with 106TCID50 ARV to evaluate the clinical signs, changes in weight gain, gross lesions, histological changes, virus replication, and serum antibody levels. The peak of clinical signs was from 3 to 5 days post infection (dpi). In addition, the death of one chicken was found in the group infected with the A18-13 isolate. Reduced body weight was also found in chickens infected with ARVs from wild birds compared to the negative control group. All the ARVs infection groups showed noticeable swelling of the footpad. In addition, ARVs were detected in the bursa, tendon, and hock joint by reverse transcription-polymerase chain reaction (RT-PCR) in all infected groups at 5 and 15 dpi. Histopathological observations revealed acute inflammatory responses on the synovium covering the joint surfaces (arthritis) and tendon sheaths (tenosynovitis), as well as bursa atrophy and lymphocyte depletion. The analysis of the humoral response was performed by ELISA assay, and chickens infected with ARVs showed seroconverted. In conclusion, this study described the typical severe disease of acute VA and tenosynovitis in SPF chickens infected with ARVs derived from wild birds. This study confirmed the pathogenicity of ARVs infection in SPF chickens for the first time, and these results enrich our understanding of the pathogenicity of ARVs derived from wild birds.

Avian reoviruses (ARVs) cause severe arthritis, tenosynovitis, pericarditis, and depressed growth in chickens, and these conditions have become increasingly frequent in recent years. Studies on the role of wild birds in the epidemiology of ARVs are insufficient. This study provides information about currently circulating ARVs in wild birds by gene detection using diagnostic RT-PCR, virus isolation, and genomic characterization. In this study, we isolated and identified 10 ARV isolates from 7,390 wild birds' fecal samples, including migratory bird species (bean goose, Eurasian teal, Indian spot-billed duck, and mallard duck) from 2015 to 2019 in South Korea. On comparing the amino acid sequences of the σC-encoding gene, most isolates, except A18-13, shared higher sequence similarity with the commercial vaccine isolate S1133 and Chinese isolates. However, the A18-13 isolate is similar to live attenuated vaccine av-S1133 and vaccine break isolates (SD09-1, LN09-1, and GX110116). For the p10- and p17-encoding genes, all isolates have identical fusion associated small transmembrane (FAST) protein and nuclear localization signal (SNL) motif to chicken-origin ARVs. Phylogenetic analysis of the amino acid sequences of the σC-encoding gene revealed that all isolates were belonged to genotypic cluster I. For the p10- and p17-encoding genes, the nucleotide sequences of all isolates indicated close relationship with commercial vaccine isolate S1133 and Chinese isolates. For the σNS-encoding gene, the nucleotide sequences of all isolates indicated close relationship with the Californian chicken-origin isolate K1600657 and belonged to chicken-origin ARV cluster. Our data indicates that wild birds ARVs were derived from the chicken farms. This finding suggests that wild birds serve as natural carriers of such viruses for domestic poultry.

With an aim to develop a highly attenuated and strongly immunogenic distinguishable vaccine candidate, a waaJ (a gene involved in the synthesis of lipopolysaccharide) and spiC (a virulence gene) double deletion Korean epidemic strain of S. enterica ser. Gallinarum (SG005) was constructed. Our results showed that the growth and biochemical characteristics were not altered by this double deletion. The double deletion strain contained dual markers. One was a bacteriological marker (rough phenotype) and the other was a serological marker helping distinguish infected chickens from vaccinated chickens. The double deletion strain showed good genetic stability and reduced resistance to environmental stresses in vitro; furthermore, it was extremely safe and highly avirulent in broilers. Single intramuscular or oral immunization of 7-day-old broilers with the double deletion strain could stimulate the body to produce antibody levels similar to the conventional vaccine strain SG9R. In addition, against a lethal wild-type challenge, it conferred effective protection that was comparable to that seen in the group vaccinated with SG9R. In conclusion, this double deletion strain may be an effective vaccine candidate for controlling S. enterica ser. Gallinarum infection in broilers.

Introduction: Sleep disorders can affect the overall health and quality of life of patients. This study was conducted to compare the differences of sleep disorders in vestibular migraine (VM) patients and benign paroxysmal positional vertigo (BPPV) patients.Methods: VM patients, BPPV patients, and healthy controls (HCs) were recruited. Pittsburgh sleep quality index and polysomnography monitoring were used as subjective and objective, respectively, evaluation methods to evaluate the sleep quality of participants in the latest month.Results: Fifty-seven BPPV patients, 48 VM patients, and 42 HCs were included in this study. There were 79.16% VM patients, 54.39% BPPV patients, and 14.28% HCs with sleep disorders. The difference in the incidence rate of sleep disorders was significant between VM patients and BPPV patients (p = 0.008) and significantly higher in both the VM group (p < 0.00001) and BPPV group (p = 0.00004) than in the HC groups (14.28%). Compared with BPPV patients, the VM patients had the significantly lower sleep efficiency (p < 0.001) and N3 (p < 0.001) and the significantly higher time of wake-up after sleep onset (p < 0.001), N1 (p < 0.001), and N2 (p < 0.001). Meanwhile, the VM patients had significantly higher incidence rates of severe obstructive sleep apnea hypoventilation syndrome (p = 0.001) and periodic leg movement in sleep (p = 0.016).Conclusion: The incidence rate of sleep disorders was significantly higher in both VM and BPPV patients than in the HC groups. To improve the curative effects, clinicians should pay more attention to the comorbidity of sleep disorders in treating VM and BPPV.

Background: Holt–Oram syndrome (HOS) is an autosomal dominant disorder caused by mutations of TBX5 gene.Case presentation: We report a fetus with HOS diagnosed sonographically at 23 weeks of gestation. The fetal parents are non-consanguineous. The fetus exhibited short radius and ulna, inability to supinate the hands, absence of the right thumb, and heart ventricular septal defect (VSD), while the fetal father exhibited VSD and short radius and ulna only. Fetal brother had cubitus valgus and thumb adduction, except for VSD, short radius and ulna. The pregnancy was terminated. Whole-exome sequencing (WES) revealed a novel mutation in the TBX5 (c.510+1G>A) in the fetus inherited from the father. The variant (c.510+1G>A) occurs at splice donor and may alter TBX5 gene function by impact on splicing. It was not previously reported in China.Conclusion: Our case reported a novel mutation in TBX5, which expanded the known genetic variants associated with HOS.

Community commitment is the key to the success of virtual communities. Under the background of virtual knowledge community, based on motivation hierarchy model and integrated emotion theory, this paper takes “motivation-emotion-community commitment” as the main framework, and introduces multiple mediation and regulation functions to establish the relationship model of motivation hierarchy, integrated emotions, and community commitment. The results show that the user motivation follows the hierarchical structure of the layer-by-layer influence from the situational level to the personality level, that is, knowledge-seeking motivation and entertainment-seeking motivation at a situational level will positively affect social- interaction motivation at the contextual level, thereby enhancing user self-efficacy at personality level. Users have abundant integrated emotions toward the virtual knowledge community, namely, satisfaction, attachment, and identity, and such multi-integrated emotional model is more conducive for promoting community commitment of users. At the same time, attachment, identity, and satisfaction have an interactive complement, that is, when satisfaction is low, attachment and identity will complement and strengthen community commitment.