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ObjectiveTo investigate the relationship between the gut microbiome and the response to anti-PD-1-based combination therapy in unresectable hepatocellular carcinoma (HCC). We aimed to identify potential non-invasive biomarkers and new strategies to modulate immunotherapy in HCC.MethodsIn this study, fresh stool samples and clinical data were collected from unresectable HCC patients treated with anti-PD-1-based combination therapy at the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2020 and December 2021. The patients were divided into two groups based on their response to treatment: the treatment responder group (R group) and the treatment non-responder group (NR group). The composition and diversity of the gut microbiome were bioinformatically analyzed by using the Whole Genome Shotgun strategy, including taxonomic composition analysis, Alpha diversity analysis, Beta diversity analysis, and differentially enriched bacterial taxa analysis. Differentially enriched bacterial taxa between R and NR groups were identified based on the magnitude of the linear discriminant analysis effect size (LEfSe) and analyzed for their impact on the survival of the patient.ResultsA total of 45 eligible patients with unresectable HCC treated with anti-PD-1-based combination therapy participated in this study. The gut microbiological composition and Alpha diversity of patients were not statistically different, but there was a statistically significant difference in Beta diversity between the R and NR groups. (PERMANOVA tests, P = 0.006). We further identified 56 enriched bacterial taxa in the R group and 44 enriched bacterial taxa in the NR group based on the LEfSe analysis (LDA >2.66, P< 0.05). Patients with a high abundance of Collinsella genus, Ruminococcus_AM4211, and Ruminococcus_AF25_28AC had a longer median PFS and median OS compared to those with low abundance (P < 0.05). On the contrary, the median PFS and OS of patients with a high abundance of Bacteroides_AF20_13LB and Veillonella_atypica were significantly shorter than those of patients with low abundance (P < 0.05). The multivariate analysis showed that the abundance of Bacteroides_AF20_13LB and Ruminococcus_ AF25_28AC was independent related factors for PFS, and the abundance of Bacteroides_AF20_13LB was an independent related factor of OS.ConclusionThe enrichment of specific gut microbiota affected clinical efficacy and survival benefits in HCC treated with anti-PD-1 therapy and may be a promising non-invasive gut microbial biomarker and a new strategy for modulating immunotherapy in HCC.

Copper is an important mineral, and moderate copper is required to maintain physiological processes in nervous system including cerebral ischemia/reperfusion (I/R) injury. Over the past few decades, copper induced cell death, named cuprotosis, has attracted increasing attention. Several lines of evidence have confirmed cuprotosis exerts pivotal role in diverse of pathological processes, such as cancer, neurodegenerative diseases, and I/R injury. Therefore, an in-depth understanding of the interaction mechanism between copper-mediated cell death and I/R injury may reveal the significant alterations about cellular copper-mediated homeostasis in physiological and pathophysiological conditions, as well as therapeutic strategies deciphering copper-induced cell death in cerebral I/R injury.

This article proposes a voltage compensation control strategy for the distribution network based on the unified power quality conditioner (UPQC) with battery energy storage systems (BESS) to achieve comprehensive management of the power quality and improve the system dynamic responses. Specifically, aiming at that amplitude and phase jump of the terminal voltage, a capacity configuration compensation scheme is proposed to achieve voltage vector compensation. The series converter is designed to compensate for the amplitude and phase of the load voltage. The parallel converter is designed to realize power compensation and ensure that the grid voltage and current are sinusoidal and in phase. A voltage control approach based on the nonlinear disturbance observer (NDO) is developed for BESS to stabilize the DC bus voltage and improve the anti-interference performance of the current. An NDO is designed to accomplish current disturbance tracking and provide disturbance feedforward compensation. Simulations validate that the proposed approach is effective and feasible.

Objectives: The aim of this study was to explore the mechanism between public services and residents’ health, focusing on the role of spatial geographical factors.Methods: Leveraging a comprehensive panel dataset encompassing 30 mainland Chinese provinces from 2007 to 2019, this study engineered a spatial Durbin model furnished with dual fixed effects through the application of the Lagrange multiplier, Hausman, and likelihood ratio tests. The primary objective was to delve into the repercussions of varying public service levels on residents’ health outcomes.Results: The empirical findings reveal a palpable spatial autocorrelation between residents’ health outcomes and the public services levels dispensed across Chinese provinces. Intriguingly, an elevation in the public service level in a given province not only ameliorates its residents’ health outcomes but also triggers a spatial spillover effect, thereby positively influencing residents’ health in neighboring provinces. The rigorous endogeneity and robustness checks affirm the reliability of the principal outcomes.Conclusion: Due to the increase in social uncertainty, all regions should break free of the administrative monopoly, enhance regional integration and development, and improve residents’ health status by clustering public service supply.

BackgroundLow-grade gliomas (LGG) are one of the most prevalent types of brain cancers. The efficacy of immunotherapy in LGG is limited compared to other cancers. Immunosuppression in the tumor microenvironment (TME) of LGG is one of the main reasons for the low efficacy of immunotherapy. Recent studies have identified 33 positive regulators of T cell functions (TPRs) that play a critical role in promoting the proliferation, activity, and functions of multiple immunocytes. However, their role in the TME of LGG has not been investigated. This study aimed to construct a risk model based on these TPRs and to detect the significance of immunotypes in predicting LGG prognosis and immunotherapy efficacy.MethodsA total of 688 LGGs and 202 normal brain tissues were extracted from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases. The NMF R package was used to identify TRP-related subtypes. The TPR prognostic model was established using the least absolute shrinkage and selection operator (LASSO) algorithm to predict the overall survival of LGG samples.ResultsThe Subtype 2 patients had worse survival outcomes, suppressed immune function, and higher immune cell infiltration. A risk regression model consisting of 14 TPRs was established, and its performance was validated in CGGA325 cohorts. The low-risk group exhibited better overall survival, immune microenvironment, and immunotherapy response, as determined via the TIDE algorithm, indicating that increasing the level of immune infiltration can effectively improve the response to immunotherapy in the low-risk group. The risk score was determined to be an independent hazard factor (p

Lung adenocarcinoma (LUAD) is the one of the most prevalent and fatal form of malignant tumors worldwide. Recently, immunotherapy is widely used in the treatment of patients with LUAD and has proved to be clinically effective in improve the prognosis of patients. But there still has been a tremendous thrust to further improve the efficacy of immunotherapy in individual patients with LUAD. The suppression of T cells and their effector functions in the tumor microenvironment (TME) of LUAD is one of the primary reasons for the low efficacy of immunotherapy in some patients with LUAD. Therefore, identifying positive regulators of T cell proliferation (TPRs) may offer novel avenues for LUAD immunotherapy. In this study, we comprehensively evaluated the infiltration patterns of TPRs in 1,066 patients with LUAD using unsupervised consensus clustering and identified correlations with genomic and clinicopathological characteristics. Three infiltrating TPR clusters were defined, and a TPR-related risk signature composed of nine TPRs was constructed using least absolute shrinkage and selection operator-Cox regression algorithms to classify the individual TPR infiltration patterns. Cluster 1 exhibited high levels of T cell infiltration and activation of immune-related signaling pathways, whereas cluster 2 was characterized by robust T cell immune infiltration and enrichment of pathways associated with carcinogenic gene sets and tumor immunity. Cluster 3 was characterized as an immune-desert phenotype. Moreover, the TPR signature was confirmed as an independent prognostic biomarker for drug sensitivity in patients with LUAD. In conclusion, the TPR signature may serve as a novel tool for effectively characterizing immune characteristics and evaluating the prognosis of patients with LUAD.

BackgroundPatients with Lynch syndrome are at an increased risk of developing simultaneous or metachronous tumors, while sarcomas have been occasionally reported. Sarcomas are generally not considered part of the common Lynch syndrome tumor spectrum. However, more and more studies and case reports suggested that sarcoma could be a rare clinical manifestation of Lynch syndrome, leading to new treatment strategies for sarcoma.Case summaryWe report the case of a 74-year-old male patient with Lynch syndrome who had rectal mucinous adenocarcinoma and prostate adenocarcinoma and then developed undifferentiated sarcoma of the left neck two years later. Mismatch repair deficiency (dMMR) was confirmed by immunohistochemical staining for the mismatch repair proteins MSH2, MSH6, MLH1 and PMS2. The result of polymerase chain reaction (PCR) microsatellite instability (MSI) testing of sarcoma showed high-level microsatellite instability (MSI-H). Additionally, a pathogenic germline mutation in MSH2 (c.2459-12A>G) was detected by next-generation sequencing (NGS). Taking into account HE morphology, immunohistochemical phenotype, MSI status, NGS result, medical history and germline MSH2 gene mutation, the pathological diagnosis of left neck biopsy tissue was Lynch syndrome related undifferentiated sarcoma with epithelioid morphology. The patient has been receiving immunotherapy (sintilimab) combined with chemotherapy (tegafur, gimeracil and oteracil potassium capsules) and currently has stable disease. We also reviewed the literature to understand the association between sarcoma and Lynch syndrome.ConclusionSarcoma may now be considered a rare clinical manifestation of Lynch syndrome. Attention and awareness about the association between Lynch syndrome and sarcoma need to be increased. Therefore, timely detection of MMR proteins and validation at the gene level for suspicious patients are the keys to avoiding missed or delayed diagnosis and to identifying patients suited for immunotherapy, which may also help to provide appropriate genetic counseling and follow-up management for patients.

In this study, we investigated the metabolism of white matter by magnetic resonance spectroscopy (MRS) in stroke complicated with diabetes mellitus in combination with glycosylated hemoglobin (HbAlc) detection and clinical neurological deficit score (NIHSS). Fifty-three patients with stroke within 24 h after onset were collected and scanned by MRS. The biochemical, clinical and imaging characteristics of patients were analyzed. Patients were divided into three groups according to HbAlc levels: Good glycemic control (A): < 6.5%; satisfactory glycemic control (B): 6.5–7.5% and poor glycemic control (C): > 7.5%. The results showed that HbA1c levels were positively correlated with NIHSS in patients with acute ischemic stroke (AIS). There is significant difference in NAA/Cr between the infarcted site of the three groups and the mirror site. HbA1C level was negatively correlated with NAA/Cr in patients with AIS, and there was no significant correlation between NIHSS score and NAA/Cr. The data above demonstrated that the MRS imaging can be used to explain the adverse effects of hyperglycated hemoglobin on brain parenchyma from the perspective of imaging. This imaging technique and clinical NIHSS score have a high consistency in evaluating stroke.

BackgroundEpigenetic regulation and immunotherapy of tumor microenvironment (TME) is a hot topic in recent years. However, the potential value of tryptophan metabolism genes in regulating TME and immunotherapy is still unclear.Materials and methodsA comprehensive study of glioma patients was carried out based on 40 tryptophan metabolic genes. Subsequently, these prognostic tryptophan metabolic genes are systematically associated with immunological characteristics and immunotherapy. A risk score model was constructed and verified in the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts to provide guidance for prognosis prediction and immunotherapy of glioma patients.ResultsWe described the changes of tryptophan metabolism genes in 966 glioma samples from genetic and transcriptional fields and evaluated their expression patterns from two independent data sets. We identified two different molecular subtypes and found that two subtypes were associated with clinicopathological features, prognosis, TME cell infiltration, and immune checkpoint blockers (ICBs). Then, four genes (IL4I1, CYP1A1, OGDHL, and ASMT) were screened out by univariate and multivariate cox regression analysis of tryptophan metabolism genes, and a risk score model for predicting the overall survival (OS) of glioma patients was constructed. And its predictive ability is verified using the CGGA database. At the same time, we verified the expression of IL4I1, CYP1A1, OGDHL, and ASMT four genes in glioma specimens and cell lines in GES4260 and GES15824. Therefore, we constructed a nomogram to improve the clinical applicability of the risk assessment model. The high risk score group, characterized by increased TMB and immune cell infiltration, was also sensitive to temozolomide immunotherapy. Our comprehensive analysis of tryptophan metabolic genes in gliomas shows that they play a potential role in tumor immune stromal microenvironment, clinicopathological features, and prognosis.ConclusionTryptophan metabolism genes play an indispensable role in the complexity, diversity, and prognosis of TME. This risk score model based on tryptophan metabolism gene is a new predictor of clinical prognosis and immunotherapy response of glioma, and guides a more appropriate immunotherapy strategy for glioma patients.

This study uses data from the China Family Panel Studies to analyze the possible impact of non-farming income on household energy choices. We use ordinary least squares and instrumental variable estimation methods to investigate the causal effect of non-farming income on household energy choices. We find that an increase in non-farming income assisted farmers in reducing their use of solid fuels in favor of clean energy. Our heterogeneity analysis, based on the average rural household income and geographical location of the village, shows that the energy upgrade effect of non-farming income is more obvious in high-income areas and suburbs closer to the county seat center. Further, we find that non-farming income has an impact on rural household energy choice mainly through the optimization of household energy-saving appliances and the enhancement of environmental awareness.

The entropy method measures the development level of green finance in 30 provinces and cities in China, and the spatial analysis method is used to describe the difference. Spatial pattern of the development level of green finance in China and empirically analyze the influencing factors of the development level of green finance. The results of the spatial econometric model show that the absolute difference in the development level of China’s green finance shows an overall increasing trend, and the relative difference shows a downward trend year by year. The level of financial development and environmental governance promote the development of green finance, while the level of economic growth and energy consumption inhibit the development of green finance. On this basis, we put forward countermeasures and suggestions from strengthening government functions and adjusting industrial structure according to economic growth, so as to promote the development of green finance in China.

In the perceptual learning of lexical tones, an automatic and robust attention-to-phonology system enables native tonal listeners to adapt to acoustically non-optimal speech, such as phonetic conflicts in daily communications. Previous tone research reveals that non-native listeners who do not linguistically employ lexical tones in their mother tongue may find it challenging to attend to the tonal dimension or integrate it with the segmental features. However, it is unknown whether the attentional interference initially caused by a maternal attentional system would continue influencing the non-optimal tone perception for simultaneous bilingual teenagers. From an endpoint in the age of language acquisition, we investigate whether the tone-specific attention mechanism developed by the Urdu-Cantonese simultaneous bilinguals is automatic enough to assist them in adapting to a phonetically-conflicting environment. Three groups of teenagers engaged in a four-condition ABX task: Urdu-Cantonese simultaneous bilinguals, Cantonese native listeners, and Urdu-speaking, late learners of Cantonese. The results showed that although the simultaneous bilinguals could phonologically process Cantonese tones in a Cantonese-like way under a conflict-free listening condition, they still failed in adapting to the phonetic conflicts, especially the segment-induced ones. It thus demonstrated that the simultaneous exposure and years of regular education in Hong Kong local schools still could not automatically guarantee simultaneous bilingual processing of Cantonese tones. In interpreting the findings, it hypothesized that, except for simultaneous exposure, the development of a tone-specific attention mechanism is also likely to be L1-inhibitory, tone experience-driven, and language-specific for simultaneous bilinguals.

Tumor mutation burden (TMB) is a useful biomarker for predicting the prognosis and efficacy of immune checkpoint inhibitor (ICIs). In this study, we aimed to explore the prognostic value of TMB and TMB-related PRLHR immune genes as prognostic markers in patients with gliomas. We downloaded MAF files, RNA-seq data, and clinical information from the Cancer Genome Atlas (TCGA) database. The TMB of glioma was calculated and its correlation with clinical features and prognosis was analyzed. We found that TMB was statistically correlated with the grade and age of patients with gliomas. Kaplan-Meier curve analysis showed that low TMB was associated with better clinical outcome in patients with gliomas. Additionally, a predictive model based on five HUB genes (FABP5, VEGFA, SAA1, ADM, and PRLHR) was constructed to predict OS in patients with gliomas. Receiver operating characteristic curve analysis shows that the model is reliable in predicting the risk of survival and prognosis. Immune microenvironment analysis revealed a correlation between TMB and infiltrating immune cells. The clinical-related immune gene, PRLHR, can be used as an independent prognostic factor for patients with brain glioma, and it is negatively correlated with the grade of glioma and age of patients with glioma. We found that the higher the tumor grade and the older the age, the lower the PRLHR expression, which was verified by CGGA database and independent experimental data. These results suggest that PRLHR may be a tumor suppressor for the progression of glioma and might provide a new therapeutic target for the treatment and improvement of survival rate in patients with glioma.

Globally, traumatic brain injury (TBI) is an acute clinical event and an important cause of death and long-term disability. However, the underlying mechanism of the pathophysiological has not been fully elucidated and the lack of effective treatment a huge burden to individuals, families, and society. Several studies have shown that long non-coding RNAs (lncRNAs) might play a crucial role in TBI; they are abundant in the central nervous system (CNS) and participate in a variety of pathophysiological processes, including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis, and neurogenesis. Some lncRNAs modulate multiple therapeutic targets after TBI, including inflammation, thus, these lncRNAs have tremendous therapeutic potential for TBI, as they are promising biomarkers for TBI diagnosis, treatment, and prognosis prediction. This review discusses the differential expression of different lncRNAs in brain tissue during TBI, which is likely related to the physiological and pathological processes involved in TBI. These findings may provide new targets for further scientific research on the molecular mechanisms of TBI and potential therapeutic interventions.

Objective: The present study aimed to investigate the effects of the dopamine receptor D4 (DRD4) −521 C/T single-nucleotide polymorphism on brain function among children with attention deficit hyperactivity disorder (ADHD) and to evaluate whether brain function is associated with behavioral performance among this demographic.Methods: Using regional homogeneity, fractional amplitude low-frequency fluctuation, and functional connectivity as measurement indices, we compared differences in resting-state brain function between 34 boys with ADHD in the TT homozygous group and 37 boys with ADHD in the C-allele carrier group. The Conners' Parent Rating Scale, the SNAP-IV Rating Scale, the Stroop Color Word Test, the go/no-go task, the n-back task, and the working memory index within the Wechsler Intelligence Scale for Children-Fourth Edition were selected as comparative indicators in order to test effects on behavioral performance.Results: We found that TT homozygotes had low behavioral performance as compared with C-allele carriers. The regional homogeneity for TT homozygotes decreased in the right middle occipital gyrus and increased in the right superior frontal gyrus as compared with C-allele carriers. In addition, the right middle occipital gyrus and the right superior frontal gyrus were used as the seeds of functional connectivity, and we found that the functional connectivity between the right middle occipital gyrus and the right cerebellum decreased, as did the functional connectivity between the right superior frontal gyrus and the angular gyrus. No statistically significant differences were observed in the respective brain regions when comparing the fractional amplitudes for low-frequency fluctuation between the two groups. Correlation analyses demonstrated that the fractional amplitude low-frequency fluctuation in the precentral gyrus for TT homozygotes were statistically significantly correlated with working memory.Conclusions: We found differing effects of DRD4 −521 C/T polymorphisms on brain function among boys with ADHD. These findings promote our understanding of the genetic basis for neurobiological differences observed among children with ADHD, but they must be confirmed in larger samples.

PDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPortal, GSCALite, PROGNOSCAN, PharmacoDB, STRING, and ENCORI databases. PBK was overexpressed in most tumors including adenocortical carcinoma (hazard ratio [HR] = 2.178, p < 0.001), kidney renal clear cell carcinoma (KIRC; HR = 1.907, p < 0.001), kidney renal papillary cell carcinoma (HR = 3.024, p < 0.001), and lung adenocarcinoma (HR = 1.255, p < 0.001), in which it was associated with poor overall survival and advanced pathologic stage. PBK methylation level was a prognostic marker in thyroid carcinoma (THCA). PBK expression was positively correlated with the levels of BIRC5, CCNB1, CDC20, CDK1, DLGAP5, MAD2L1, MELK, PLK1, TOP2A, and TTK in 32 tumor types; and with the levels of the transcription factors E2F1 and MYC, which regulate apoptosis, the cell cycle, cell proliferation and invasion, tumorigenesis, and metastasis. It was also negatively regulated by the microRNAs hsa-miR-101-5p, hsa-miR-145-5p, and hsa-miR-5694. PBK expression in KIRC, liver hepatocellular carcinoma, THCA, and thymoma was positively correlated with the infiltration of immune cells including B cells, CD4+T cells, CD8+ T cells, macrophages, monocytes, and neutrophils. The results of the functional enrichment analysis suggested that PBK and related genes contribute to tumor development via cell cycle regulation. We also identified 20 drugs that potentially inhibit PBK expression. Thus, PBK is associated with survival outcome in a variety of cancers and may promote tumor development and progression by increasing immune cell infiltration into the tumor microenvironment. These findings indicate that PBK is a potential therapeutic target and has prognostic value in cancer treatment.

The incidence of head and neck squamous cell carcinoma (HNSC) is increasing year by year. The nerve is an important component of the tumor microenvironment, which has a wide range of cross-talk with tumor cells and immune cells, especially in highly innervated organs, such as head and neck cancer and pancreatic cancer. However, the role of cancer-nerve cross-talk-related genes (NCCGs) in HNSC is unclear. In our study, we constructed a prognostic model based on genes with prognostic value in NCCGs. We used Pearson’s correlation to analyze the relationship between NCCGs and immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. We used single-cell sequencing data to analyze the expression of genes associated with stage in different cells and explored the possible pathways affected by these genes via gene set enrichment analysis. In the TCGA-HNSC cohort, a total of 23 genes were up- or downregulated compared with normal tissues. GO and KEGG pathway analysis suggested that NCCGs are mainly concentrated in membrane potential regulation, chemical synapse, axon formation, and neuroreceptor-ligand interaction. Ten genes were identified as prognosis genes by Kaplan-Meier plotter and used as candidate genes for LASSO regression. We constructed a seven-gene prognostic model (NTRK1, L1CAM, GRIN3A, CHRNA5, CHRNA6, CHRNB4, CHRND). The model could effectively predict the 1-, 3-, and 5-year survival rates in the TCGA-HNSC cohort, and the effectiveness of the model was verified by external test data. The genes included in the model were significantly correlated with immune infiltration, microsatellite instability, tumor mutation burden, drug sensitivity, and clinical stage. Single-cell sequencing data of HNSC showed that CHRNB4 was mainly expressed in tumor cells, and multiple metabolic pathways were enriched in high CHRNB4 expression tumor cells. In summary, we used comprehensive bioinformatics analysis to construct a prognostic gene model and revealed the potential of NCCGs as therapeutic targets and prognostic biomarkers in HNSC.

Listeners utilize the immediate contexts to efficiently normalize variable vocal streams into standard phonology units. However, researchers debated whether non-speech contexts can also serve as valid clues for speech normalization. Supporters of the two sides proposed a general-auditory hypothesis and a speech-specific hypothesis to explain the underlying mechanisms. A possible confounding factor of this inconsistency is the listeners’ perceptual familiarity of the contexts, as the non-speech contexts were perceptually unfamiliar to listeners. In this study, we examined this confounding factor by recruiting a group of native Cantonese speakers with sufficient musical training experience and a control group with minimal musical training. Participants performed lexical tone judgment tasks in three contextual conditions, i.e., speech, non-speech, and music context conditions. Both groups were familiar with the speech context and not familiar with the non-speech context. The musician group was more familiar with the music context than the non-musician group. The results evidenced the lexical tone normalization process in speech context but not non-speech nor music contexts. More importantly, musicians did not outperform non-musicians on any contextual conditions even if the musicians were experienced at pitch perception, indicating that there is no noticeable transfer in pitch perception from the music domain to the linguistic domain for tonal language speakers. The findings showed that even high familiarity with a non-linguistic context cannot elicit an effective lexical tone normalization process, supporting the speech-specific basis of the perceptual normalization process.

PurposeTo evaluate the efficacy and toxicity of the two IC (induction chemotherapy) regimens, TPF (taxanes, cisplatin, and 5-fluorouracil) and TP (taxanes and cisplatin) combined with concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients.MethodsUltimately, we enrolled 213 patients at stage III-IVA in this retrospective study. The prognosis of TPF and TP was compared by Kaplan-Meier and Cox proportional hazard regression. The toxicities were evaluated according to CTCAE v4.0 and RTOG criteria.ResultsTPF was found to have a higher 5-year DMFS in stage IVA and N2-3 patients. The optimal value of pretreatment SII was 432.48. A further subgroup analysis revealed that patients in stage IVA combined with SII ≥432.48 showed superior OS (P=0.038) and DMFS (P=0.028) from TPF. Also, SII was proved to be a prognostic element for PFS (HR 2.801, P=0.018) and DMFS (HR 3.735, P=0.032) in multivariate analysis, and IC regimen (HR 2.182, P=0.049) for predicting DMFS. The rate of grade 3–4 leukopenia (P=0.038), neutropenia (P=0.021), radiation oral mucositis (P=0.048), diarrhea (P=0.036), and ear damage (P=0.046) were more common in TPF group.ConclusionOur study revealed that TPF regimen showed a higher 5-year DMFS for stage IVA and N2-3 patients, while for stage III and N0-1, TP might be ample. In high-risk LA-NPC patients (stage IVA combined with pretreatment SII ≥432.48), TPF had a higher 5-year OS and DMFS, with more grade 3–4 toxicities, but most of them were endurable.

Objective: This study investigates whether the dynamic functional connectivity (dFC) of the amygdala subregions is altered in children with attention-deficit/hyperactivity disorder (ADHD).Methods: The dFC of the amygdala subregions was systematically calculated using a sliding time window method, for 75 children with ADHD and 20 healthy control (HC) children.Results: Compared with the HC group, the right superficial amygdala exhibited significantly higher dFC with the right prefrontal cortex, the left precuneus, and the left post-central gyrus for children in the ADHD group. The dFC of the amygdala subregions showed a negative association with the cognitive functions of children in the ADHD group.Conclusion: Functional connectivity of the amygdala subregions is more unstable among children with ADHD. In demonstrating an association between the stability of functional connectivity of the amygdala and cognitive functions, this study may contribute by providing a new direction for investigating the internal mechanism of ADHD.

BackgroundIn this study, we evaluated the prognostic value of the plasma levels of Epstein-Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma (NPC) at different treatment stages.MethodsWe retrospectively analyzed the Data of 206 patients with NPC. Pre-neoadjuvant chemotherapy (pre-NACT), post-NACT, post-radiotherapy, and post-treatment plasma EBV DNA levels were used to establish prognostic nomograms. The concordance index (C-index) and calibration curves were used to compare the prognostic accuracy of the nomograms. The results were confirmed in a validation cohort consisting of patients who were tested for EBV DNA levels at all four stages of treatment. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Survival differences were calculated using the log-rank test.ResultsEBV DNA-positive patients had worse 3-year PFS and 5-year OS than EBV DNA-negative patients; this was true for pre-NACT (PFS: 82.7% vs. 57.3%, P < 0.001; OS: 90.9% vs. 68.7%, P = 0.08) and post-NACT (PFS: 85.0% vs. 50.6%, P < 0.001; OS: 91.7% vs. 65.7%; P = 0.001) EBV DNA levels but not for post-radiotherapy (PFS: 72.2% vs. 60.9%, P = 0.192; OS: 73.1% vs. 77.2%, P = 0.472) or post-treatment (PFS: 77.3% vs. 59.2%, P = 0.063; OS: 77.5% vs. 79.7%, P = 0.644) levels. Nomograms combining pre-NACT and post-NACT EBV DNA levels had a superior prognostic ability than those of post-radiotherapy and post-treatment EBV DNA levels.ConclusionPre-NACT EBV DNA levels combined with post-NACT EBV DNA levels can more reliably predict survival outcomes in patients with NPC.

Gliomas are characterized by high incidence, recurrence and mortality all of which are significant challenges to efficacious clinical treatment. The hypoxic microenvironment in the inner core and intermediate layer of the tumor mass of gliomas is a critical contributor to glioma pathogenesis. In this study, we identified an upregulated lncRNA, OR7E156P, in glioma was identified. The silencing of OR7E156P inhibited cell invasion and DNA synthesis in vitro and tumor growth in vivo. OR7E156P was intricately linked to the HIF1A pathway. Hypoxia could induce OR7E156P expression, whereas OR7E156P silencing decreased HIF1A protein levels under hypoxic conditions. Hypoxia promoted glioma cell invasion and DNA synthesis, and HUVEC tube formation, whereas OR7E156P silencing partially reversed the cellular effects of hypoxia. HIF1A overexpression promoted, whereas OR7E156P silencing inhibited tumor growth; the inhibitory effects of OR7E156P silencing on tumor growth were partially reversed by HIF1A overexpression. miR-143 directly targeted OR7E156P and HIF1A, respectively. miR-143 inhibition increased HIF1A protein levels, promoted glioma cell invasion and DNA synthesis. Moreover, they enhanced HUVEC tube formation, whereas OR7E156P silencing partially reversed the cellular effects of miR-143 inhibition. HIF1A targeted the promoter region of miR-143 and inhibited miR-143 expression. Altogether a regulatory axis consisting of OR7E156P, miR-143, and HIF1A, was identified which is deregulated in glioma, and the process of the OR7E156P/miR-143/HIF1A axis modulating glioma cell invasion through ZEB1 and HUVEC tube formation through VEGF was demonstrated.

Blood collection for newborn genetic disease screening is preferably performed within 24–48 h after birth. We used population-level newborn screening (NBS) data to study early postnatal metabolic changes and whether timing of blood collection could impact screening performance. Newborns were grouped based on their reported age at blood collection (AaBC) into early (12–23 h), standard (24–48 h), and late (49–168 h) collection groups. Metabolic marker levels were compared between the groups using effect size analysis, which controlled for group size differences and influence from the clinical variables of birth weight and gestational age. Metabolite level differences identified between groups were correlated to NBS data from false-positive cases for inborn metabolic disorders including carnitine transport defect (CTD), isovaleric acidemia (IVA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Our results showed that 56% of the metabolites had AaBC-related differences, which included metabolites with either decreasing or increasing levels after birth. Compared to the standard group, the early-collection group had elevated marker levels for PKU (phenylalanine, Cohen's d = 0.55), IVA (C5, Cohen's d = 0.24), MMA (C3, Cohen's d = 0.23), and CTD (C0, Cohen's d = 0.23). These findings correlated with higher false-positive rates for PKU (P < 0.05), IVA (P < 0.05), and MMA (P < 0.001), and lower false-positive rate for CTD (P < 0.001) in the early-collection group. Blood collection before 24 h could affect screening performance for some metabolic disorders. We have developed web-based tools integrating AaBC and other variables for interpretive analysis of screening data.

Previous studies have shown that for congenital amusics, long-term tone language experience cannot compensate for lexical tone processing difficulties. However, it is still unknown whether such difficulties are merely caused by domain-transferred insensitivity in lower-level acoustic processing and/or by higher-level phonological processing of linguistic pitch as well. The current P300 study links and extends previous studies by uncovering the neurophysiological mechanisms underpinning lexical tone perception difficulties in Mandarin-speaking amusics. Both the behavioral index (d′) and P300 amplitude showed reduced within-category as well as between-category sensitivity among the Mandarin-speaking amusics regardless of the linguistic status of the signal. The results suggest that acoustic pitch processing difficulties in amusics are manifested profoundly and further persist into the higher-level phonological processing that involves the neural processing of different lexical tone categories. Our findings indicate that long-term tone language experience may not compensate for the reduced acoustic pitch processing in tone language speakers with amusia but rather may extend to the neural processing of the phonological information of lexical tones during the attentive stage. However, from both the behavioral and neural evidence, the peakedness scores of the d′ and P300 amplitude were comparable between amusics and controls. It seems that the basic categorical perception (CP) pattern of native lexical tones is preserved in Mandarin-speaking amusics, indicating that they may have normal or near normal long-term categorical memory.

Lower-grade gliomas (LrGG), characterized by invasiveness and heterogeneity, remain incurable with current therapies. Clinicopathological features provide insufficient information to guide optimal individual treatment and cannot predict prognosis completely. Recently, an increasing amount of studies indicate that the tumor microenvironment plays a pivotal role in tumor malignancy and treatment responses. However, studies focusing on the tumor microenvironment (TME) of LrGG are still limited. In this study, taking advantage of the currently popular computational methods for estimating the infiltration of tumor-associated normal cells in tumor samples and using weighted gene co-expression network analysis, we screened the co-expressed gene modules associated with the TME and further identified the prognostic hub genes in these modules. Furthermore, eight prognostic hub genes (ARHGDIB, CLIC1, OAS3, PDIA4, PARP9, STAT1, TAP2, and TAGLN2) were selected to construct a prognostic risk score model using the least absolute shrinkage and selection operator method. Univariate and multivariate Cox regression analysis demonstrated that the risk score was an independent prognostic factor for LrGG. Moreover, time-dependent ROC curves indicated that our model had favorable efficiency in predicting both short- and long-term prognosis in LrGG patients, and the stratified survival analysis demonstrated that our model had prognostic value for different subgroups of LrGG patients. Additionally, our model had potential value for predicting the sensitivity of LrGG patients to radio- and chemotherapy. Besides, differential expression analysis showed that the eight genes were aberrantly expressed in LrGG compared to normal brain tissue. Correlation analysis revealed that the expression of the eight genes was significantly associated with the infiltration levels of six types of immune cells in LrGG. In summary, the TME-related eight-gene signature was significantly associated with the prognosis of LrGG patients. They might act as potential prognostic biomarkers for LrGG patients, offer better stratification for future clinical trials, and be candidate targets for immunotherapy, thus deserving further investigation.

Speech variability facilitates non-tonal language speakers’ lexical tone learning. However, it remains unknown whether tonal language speakers can also benefit from speech variability while learning second language (L2) lexical tones. Researchers also reported that the effectiveness of speech variability was only shown on learning new items. Considering that the first language (L1) and L2 probably share similar tonal categories, the present study hypothesizes that speech variability only promotes the tonal language speakers’ acquisition of L2 tones that are different from the tones in their L1. To test this hypothesis, the present study trained native Mandarin (a tonal language) speakers to learn Cantonese tones with either high variability (HV) or low variability (LV) speech materials, and then compared their learning performance. The results partially supported this hypothesis: only Mandarin subjects’ productions of Cantonese low level and mid level tones benefited from the speech variability. They probably relied on the mental representations in L1 to learn the Cantonese tones that had similar Mandarin counterparts. This learning strategy limited the impact of speech variability. Furthermore, the results also revealed a discrepancy between L2 perception and production. The perception improvement may not necessarily lead to an improvement in production.

Objective: Ventricular infection from multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is one of the most severe complications of craniotomy. However, the availability of effective therapeutic options for these infections is limited. Thus, this report aims to describe the efficacy of abscess clearance by intraventricular and intravenous tigecycline therapy in managing patients with multidrug-resistant A. baumannii ventriculitis after neurosurgery. Moreover, the current literature on the use of tigecycline therapy for these life-threatening infections is reviewed and summarized, and a treatment regimen based on the available data is proposed.Methods: A patient with multidrug-resistant A. baumannii ventriculitis was admitted in our hospital and was provided with a detailed therapeutic schedule. Tigecycline treatments for multidrug-resistant A. baumannii ventriculitis that were reported in the literature were also reviewed and summarized.Results: The patient in our hospital underwent abscess clearance on a ventriculoscope and was subsequently subjected to multi-route tigecycline therapy 14 days after the start of the continuous ventricular irrigation (CVI) tigecycline and 3 days after the intraventricular (IVT) tigecycline. The signs of ventriculitis disappeared, and the Acinetobacter cerebrospinal fluid (CSF) load steadily decreased until CSF sterilization. Literature review identified seven cases of ventricular infection from multidrug-resistant A. baumannii treated with tigecycline. In the eight cases, all patients were male adults (>18 years), with a mean age of 46.1 (range: 22–75) years. Meningitis/ventriculitis was secondary to neurosurgery procedures for the management of various central nervous system diseases in all cases. A good clinical outcome was achieved in all eight patients with multidrug-resistant A. baumannii meningitis/ventriculitis treated with CVI and/or IVT tigecycline, and any relevant complications were not observed.Conclusions: CVI and IVT tigecycline and IVT colistin could be considered as the first-line therapy in patients with ventricular infections from MDR/extreme drug-resistant A. baumannii. However, more studies should be conducted to confirm our observation.

Previous studies on congenital amusia mainly focused on the impaired fronto-temporal pathway. It is possible that neural pathways of amusia patients on a larger scale are affected. In this study, we investigated changes in structural connections by applying both tract-based and network-based analysis to DTI data of 12 subjects with congenital amusia and 20 demographic-matched normal controls. TBSS (tract-based spatial statistics) was used to detect microstructural changes. The results showed that amusics had higher diffusivity indices in the corpus callosum, the right inferior/superior longitudinal fasciculus, and the right inferior frontal-occipital fasciculus (IFOF). The axial diffusivity values of the right IFOF were negatively correlated with musical scores in the amusia group. Network-based analysis showed that the efficiency of the brain network was reduced in amusics. The impairments of WM tracts were also found to be correlated with reduced network efficiency in amusics. This suggests that impaired WM tracts may lead to the reduced network efficiency seen in amusics. Our findings suggest that congenital amusia is a disconnection syndrome.

Male occult triple-negative breast cancer (TNBC) is an exceedingly rare form of breast cancer, and prospective information regarding its management is therefore lacking. Current treatment strategies are largely extrapolated from clinical trials of female breast cancer, leading to substantial knowledge gaps concerning the optimal management of male breast cancer. Here, we present a male patient with occult TNBC who responded to immunotherapy, with an obvious reduction in his tumor burden following antiandrogen therapy, after heavy treatment with several lines of chemotherapy. This case highlights the potential efficacy of immunotherapy in cases of male TNBC and suggests a role for antiandrogen therapy in managing patients with luminal androgen receptor-positive TNBC.

Nickel foam (NF) with a three-dimensional porous structure plays an important role in a wide variety of applications such as energy storage and conversion, catalysis, and sensor due to its high porosity, low density, and excellent conductivity. However, the main drawback of NF is that its ligaments are very smooth, and thus the surface area is relatively low. In this work, we propose a novel strategy, oxidization and reduction process, in situ to construct micron/nano pores on the ligaments of commercial NF to fabricate a typical hierarchical porous architecture. This process is simple and green, avoiding the use of sacrificial materials. Furthermore, MnO2 is coated on the micron/nano-porous Ni foam (MPNF) to construct an oxygen evolution reaction (OER) electrode through pulse electrodeposition. The designed MPNF-MnO2 electrode presents enhanced OER electrocatalysis activity with a low overpotential of 363.5 mV at the current density of 10 mA cm−2 in an alkaline solution, which is 66.4 mV lower than that of the NF-MnO2 electrode in the same operating conditions. Furthermore, the porous and wrinkled structures of the MPNF also improve the mechanical integrity of the electrode, resulting in super-long stability.