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Abstract Objective To investigate the correlation between MRI findings and histological features for preoperative prediction of histological grading and Ki-67 expression level in alveolar soft part sarcoma (ASPS). Methods A retrospective analysis was conducted on 63 ASPS patients (Jan 2017–May 2023). All patients underwent 3.0-T MRI examinations, including conventional sequences, dynamic contrast-enhanced scans with time-intensity curve analysis, and diffusion-weighted imaging with apparent diffusion coefficient (ADC) measurements. Patients were divided into low-grade (histological Grade I) and high-grade (histological Grade II/III) groups based on pathology. Immunohistochemistry was used to assess Ki-67 expression levels in ASPS. Statistical analysis included chi-square tests, Wilcoxon rank-sum test, binary logistic regression analysis, Spearman correlation analysis, and receiver operating characteristic curve analysis of various observational data. Results There were 29 low-grade and 34 high-grade patients (26 males and 37 females) and a wide age range (5–68 years). Distant metastasis, tumor enhancement characteristics, and ADC values were independent predictors of high-grade ASPS. High-grade ASPS had lower ADC values (p = 0.002), with an area under the curve (AUC), sensitivity, and specificity of 0.723, 79.4%, and 58.6%, respectively, for high-grade prediction. There was a negative correlation between ADC values and Ki-67 expression (r = −0.526; p

Abstract Background The study aimed to assess the impact of parotid lymph nodes (LNs) on the prognosis of patients with cutaneous squamous cell carcinomas of the head and neck (HNcSCC), and to develop an alternative LN assessment method to enhance locoregional control (LRC) and overall survival (OS) stratification. Methods We retrospectively enrolled patients with surgically treated HNcSCC. Primary outcome variables were LRC and OS. The influence of parotid LNs and different LN assessment methods on prognosis was analyzed using Cox models, and comparisons were made using the C-index, Akaike Information Criterion, and Bayesian Information Criterion. Results A total of 126 patients were included. Both intraparotid and periparotid LN statuses significantly linked with prognosis. The presence of extranodal extension (ENE) in cervical LNs, rather than parotid LNs, was predictive of decreased LRC and OS. In the Cox analysis, only N3 of the AJCC N classification, when compared to N0, showed reduced LRC and OS. In comparison to N0P1, only N0P3/N1P1 and N2P2/N2P3 of the O’Brien staging system tended to predict poorer LRC, with no subgroup emerging as an independent predictor for OS. The proposed LN assessment method, based on the number of metastatic LNs and ENE status in cervical LNs, demonstrated superior performance in terms of C-index, Akaike Information Criterion, and Bayesian Information Criterion compared to other systems. Conclusion Parotid LNs were significant determinants of prognosis in metastatic HNcSCC. The novel LN assessment method proposed (1–2 vs. 3–4 vs. 5 + or ENE) displayed similar survival stratification to the AJCC N and O’Brien staging systems.

Neonatal sepsis is a major global health challenge, leading to significant morbidity and mortality in newborns. The search for precise biomarkers for its early prediction in clinical settings has been ongoing, with heparin-binding protein (HBP) emerging as a promising candidate. Originating from granules in neutrophils, HBP is released into the bloodstream in response to infection and plays a pivotal role in the body’s inflammatory response. Its significance extends beyond its inflammatory origins; research indicates dynamic changes in HBP levels are strongly linked to reduce in-hospital mortality, offering a prognostic advantage over existing biomarkers. Furthermore, HBP has demonstrated considerable clinical utility in the early diagnosis and stratification of neonatal sepsis, suggesting its potential as a reliable blood marker for early prediction of the disease and its severity. Its application may extend to guiding the judicious use of antibiotics in treating newborns, addressing a critical aspect of neonatal care. Despite these encouraging results, the precise clinical utility of HBP for diagnosing and treating sepsis in neonates still demands further clarification through extensive research. This review delves into the current scientific understanding of HBP’s contribution to diagnosing, prognosticating, and treating neonatal sepsis, while considering its future clinical applications.

Neonatal varicella is indeed a rare condition, and most infants born to mothers with varicella have a good prognosis. However, in exceptional cases, neonatal varicella can be life-threatening, particularly for preterm infants. Therefore, it is vital to make an early diagnosis or predict the risk of neonatal varicella to ensure prompt treatment and improve prognosis. This report made an effort to early predict neonatal vericalla by using metagenomic next-generation sequencing (mNGS) in a preterm infant who was at risk for vericalla infection. A preterm infant born from a mother with varicella with symptom onset at 8 days before delivery, putting the infant at risk for varicella infection. Importantly, the patient develop pneumonia and pneumothorax, and neonatal vericella was suspected. Fortunately, the use of mNGS for testing the varicella gene in the serum promptly ruled out varicella zoster virus (VZV) infection in the patient, as indicated by a negative mNGS result. Subsequent follow-up, which included a 14-day stay in the hospital followed by an additional 7 days at home, confirmed this finding. Throughout this period, the patient did not exhibit any rash or other symptoms associated with varicella. Therefore, the novel approach of using mNGS allows neonatologists to predict and promptly address potential neonatal infections. This early detection is crucial, as delayed diagnosis or treatment could pose life-threatening risks, as exemplified by the case of neonatal varicella. In such cases, neonatologists can take proactive measures instead of standing by for at-risk neonates. Furthermore, given the severity of neonatal varicella as a life-threatening condition, the early exclusion of subsequent varicella infection by mNGS can offer reassurance to both family members and healthcare professionals.

Abstract Background and Objectives The GAA repeat expansion within the fibroblast growth factor 14 (FGF14) gene has been found to be associated with late‐onset cerebellar ataxia. This study aimed to investigate the genetic causes of cerebellar ataxia in patients in Japan. Methods We collected a case series of 940 index patients who presented with chronic cerebellar ataxia and remained genetically undiagnosed after our preliminary genetic screening. To investigate the FGF14 repeat locus, we employed an integrated diagnostic strategy that involved fluorescence amplicon length analysis polymerase chain reaction (PCR), repeat‐primed PCR, and long‐read sequencing. Results Pathogenic FGF14 GAA repeat expansions were detected in 12 patients from 11 unrelated families. The median size of the pathogenic GAA repeat was 309 repeats (range: 270–316 repeats). In these patients, the mean age of onset was 66.9 ± 9.6 years, with episodic symptoms observed in 56% of patients and parkinsonism in 30% of patients. We also detected FGF14 repeat expansions in a patient with a phenotype of multiple system atrophy, including cerebellar ataxia, parkinsonism, autonomic ataxia, and bilateral vocal cord paralysis. Brain magnetic resonance imaging (MRI) showed normal to mild cerebellar atrophy, and a follow‐up study conducted after a mean period of 6 years did not reveal any significant progression. Discussion This study highlights the importance of FGF14 GAA repeat analysis in patients with late‐onset cerebellar ataxia, particularly when they exhibit episodic symptoms, or their brain MRI shows no apparent cerebellar atrophy. Our findings contribute to a better understanding of the clinical variability of GAA‐FGF14‐related diseases.

Abstract Due to its non‐invasive nature, ultrasound has been widely used for neuromodulation in biological systems, where its application influences the synaptic weights and the process of neurotransmitter delivery. However, such modulation has not been emulated in physical devices. Memristors are ideal electrical components for artificial synapses, but up till now they are hardly reported to respond to ultrasound signals. Here we design and fabricate a HfOx‐based memristor on 64°Y‐X LiNbO3 single crystal substrate, and successfully realize artificial synapses modulation by shear‐horizontal surface acoustic wave (SH‐SAW). It is a prominent short‐term resistance modulation, where ultrasound has been shown to cause resistance drop for various resistance states, which could fully recover after the ultrasound is shut off. The physical mechanism illustrates that ultrasound induced polarization potential in the HfOx dielectric layer acts on the Schottky barrier, leading to the resistance drop. The emulation of neuron firing frequency modulation through ultrasound signals is demonstrated. Moreover, the joint application of ultrasound and electric voltage yields fruitful functionalities, such as the enhancement of resistance window and synaptic plasticity through ultrasound application. All these promising results provide a new strategy for artificial synapses modulation, and also further advance neuromorphic devices toward system applications.

Severe neonatal hyponatremia represents a critical electrolyte imbalance with potentially severe neurological outcomes, a condition rarely documented in community-acquired, full-term newborns. This report underscores a unique case of a 23-day-old, previously healthy, full-term male neonate experiencing severe hyponatremia that precipitated seizures, underscoring the urgency of prompt recognition and intervention. The neonate presented with symptoms including vomiting, groaning, chills, fixed staring, and limb tremors. Critical findings upon admission encompassed hypothermia, hypotension, tachycardia, and tachypnea accompanied by significant weight loss. The clinical presentation was marked by dehydration, lethargy, weak crying, a fixed gaze, irregular breathing, and coarse lung sounds, yet a distended abdomen, hypertonic limb movements, and recurrent seizures were observed. Immediate interventions included establishing IV access, rewarming, mechanical ventilation, seizure management, volume expansion, dopamine for circulatory support, and initiation of empirical antibiotics. Diagnostic evaluations revealed a sodium ion concentration of 105.9 mmol/L, while amplitude-integrated electroencephalography (aEEG) detected pronounced seizure activity characterized by a lack of sleep-wake rhythmicity, noticeable elevation in both the lower and upper amplitude margins, and a sustained decrease in the lower margin voltage dropping below 5 μV, presenting as sharp or serrated waveforms. The management strategy entailed rapid electrolyte normalization using hypertonic saline and sodium bicarbonate, anticonvulsant therapy, and comprehensive supportive care, with continuous aEEG monitoring until the cessation of seizures. Remarkably, by the third day, the neonate’s condition had stabilized, allowing for discharge in good health 10 days post-admission. At a 16-month follow-up, the child exhibited no adverse neurological outcomes and demonstrated favorable growth and development. Our extensive review on the etiology, clinical manifestations, aEEG monitoring, characteristics of seizures induced by severe neonatal hyponatremia, treatment approaches, and the prognosis for seizures triggered by severe hyponatremia aims to deepen the understanding and enhance clinical management of this complex condition. It stresses the importance of early detection, accurate diagnosis, and customized treatment protocols to improve outcomes for affected neonates. Additionally, this review accentuates the indispensable role of aEEG monitoring in managing neonates at elevated risk for seizures. Yet, the safety and efficacy of swiftly administering hypertonic saline for correcting severe hyponatremia-induced seizures necessitate further investigation through medical research.

Ceftriaxone is widely used in pediatric outpatient care for its efficacy against respiratory and digestive system infections, yet its increasing association with severe immune hemolytic reactions requires heightened vigilance from pediatricians. This report details a rare and severe case of ceftriaxone-induced severe immune hemolytic anemia (IHA), hemolytic crisis, myocardial injury, liver injury, renal calculi, and cholecystolithiasis in a previously healthy 3-year-old child. The child, treated for bronchitis, experienced sudden pallor, limb stiffness, and altered consciousness following the fifth day of ceftriaxone infusion, with hemoglobin (Hb) levels precipitously dropping to 21 g/L. Immediate cessation of ceftriaxone and the administration of oxygen therapy, blood transfusion, intravenous immunoglobulin (IVIG), and corticosteroids led to a gradual recovery. Despite initial improvements, the patient’s condition necessitated extensive hospital care due to complications including myocardial injury, liver injury, renal calculi, and cholecystolithiasis. After a 12-day hospital stay and a 3-month follow-up, the child showed complete normalization of Hb and liver function and resolution of calculi. In children, ceftriaxone infusion may trigger severe, potentially fatal, hemolytic reactions. Pediatricians must promptly recognize symptoms such as pallor, limb stiffness, and unresponsiveness, indicative of ceftriaxone-induced severe IHA, and immediately discontinue the drug. Effective management includes timely blood transfusion, respiratory support, IVIG administration, and corticosteroids when necessary, along with rigorous vital signs monitoring. Continued vigilance is imperative, even after cessation of ceftriaxone, to promptly address any residual adverse effects.

A scientific performance evaluation model is necessary to establish a performance evaluation index system for compulsory education in ethnic areas and to conduct objective and impartial evaluations. After conducting theoretical analysis and reviewing literature, it was determined that existing educational input performance evaluation models are general and fail to reflect the unique characteristics of compulsory education development in ethnic areas of China. Therefore, this study intends to improve their self-adaptability and degree of fit. Based on the features of China's ethnic areas and the current situation of compulsory education development, a trinity evaluation model of compulsory education input performance in ethnic regions was constructed using the classical performance evaluation theoretical framework. This model includes the “implementation topic - target concept - performance dimension.'' The government is the main organization responsible for organizing and implementing the entire performance evaluation, with publicness and responsiveness as the value idea of evaluation. The “4E″ of enough, equity, efficiency, and effectiveness are the evaluation objectives, and input, allocation, output, and effect are the dimensions of the building of the performance evaluation index system. The “4E″ evaluation objectives are integrated into the performance evaluation dimensions and index system. The reconstructed theoretical model of performance evaluation combines universality and specificity, highlights the dual attributes of “tool-value,'' realizes the organic combination of internal and external performance evaluation, illustrates the overall performance evaluation process and ensures objective, fair, and accurate performance evaluation results. It provides useful guidelines for further optimizing compulsory education investment policies and promoting high-quality and well-balanced compulsory education in China's ethnic areas.

BackgroundThe aim of this study was to analyze the impact of the number and extranodal extension (ENE) of positive parotid lymph nodes (LNs) on distant metastasis in parotid cancer.MethodsPatients with surgically treated parotid cancer were retrospectively enrolled. The hazard ratios (HRs) of the number and ENE of positive parotid LNs on distant metastasis-free survival (DMFS) were evaluated.ResultsIn the Cox model, the groups with zero and one positive LN had comparable 10-year DMFS, but those with two positive LNs had an HR of 2.11 (95% CI: 1.36–5.29), and those with three or more positive LNs had an HR of 3.31 (95% CI: 2.05–8.43). The presence of ENE in parotid LNs did not impact the DMFS (p = 0.462; HR: 2.17; 95% CI: 0.84–6.17).ConclusionParotid LN metastasis was associated with decreased DMFS; this effect was mainly driven by the number of positive LNs rather than ENE.

Tree peony (Paeonia ostii) has the largest chromosome of any sequenced plants to date. Here, the authors assemble its genome and reveal the association of a list of candidate genes with fatty acid biosynthesis and the possible contribution of transposon and histone expansion to maintain the giga-chromosomes.

Abstract Background Recessive mutations in SLC12A6 have been linked to hereditary motor sensory neuropathy with agenesis of the corpus callosum. Patients with early‐onset peripheral neuropathy associated with SLC12A6 heterozygous variants were reported in 2016. Only five families and three variants have been reported to date, and the spectrum is unclear. Here, we aim to describe the clinical and mutation spectra of SLC12A6‐related Charcot–Marie–Tooth (CMT) disease in Japanese patients. Methods We extracted SLC12A6 variants from our DNA microarray and targeted resequencing data obtained from 2598 patients with clinically suspected CMT who were referred to our genetic laboratory by neurological or neuropediatric departments across Japan. And we summarized the clinical and genetic features of these patients. Results In seven unrelated families, we identified one previously reported and three novel likely pathogenic SLC12A6 heterozygous variants, as well as two variants of uncertain significance. The mean age of onset for these patients was 17.5 ± 16.1 years. Regarding electrophysiology, the median motor nerve conduction velocity was 39.6 ± 9.5 m/sec. For the first time, we observed intellectual disability in three patients. One patient developed epilepsy, and her brain MRI revealed frontal and temporal lobe atrophy without changes in white matter and corpus callosum. Conclusions Screening for the SLC12A6 gene should be considered in patients with CMT, particularly those with central nervous system lesions, such as cognitive impairment and epilepsy, regardless of the CMT subtype.

Paeonia ostii, a widely cultivated tree peony species in China, is a resourceful plant with medicinal, ornamental and oil value. However, fleshy roots lead to a low tolerance to waterlogging in P. ostii. In this study, P. ostii roots were sequenced using a hybrid approach combining single-molecule real-time and next-generation sequencing platforms to understand the molecular mechanism underlying the response to this sequentially waterlogging stress, the normal growth, waterlogging treatment (WT), and waterlogging recovery treatment (WRT). Our results indicated that the strategy of P. ostii, in response to WT, was a hypoxic resting syndrome, wherein the glycolysis and fermentation processes were accelerated to maintain energy levels and the tricarboxylic acid cycle was inhibited. P. ostii enhanced waterlogging tolerance by reducing the uptake of nitrate and water from the soil. Moreover, transcription factors, such as AP2/EREBP, WRKY, MYB, and NAC, played essential roles in response to WT and WRT. They were all induced in response to the WT condition, while the decreasing expression levels were observed under the WRT condition. Our results contribute to understanding the defense mechanisms against waterlogging stress in P. ostii.

ObjectivesTo determine the predictor for occult neck metastases and the role of elective neck dissection (END) in cT3-4N0 parotid adenoid cystic carcinoma (ACC).MethodsPatients with surgically treated parotid ACC were retrospectively enrolled. Predictors of occult neck metastases and the effect of END on disease specific survival (DSS), overall survival (OS), locoregional control survival (LRC), and distant metastasis free survival (DMS) were analyzed.ResultsOccult neck metastases occurred in 35 (19.7%) of the 178 patients undergoing an END. The tumor stage [p=0.011, 4.215 (1.387–10.435)] and intra-parotid lymph node metastasis [p=0.032, 3.671 (1.693–8.775)] were related to the possibility of occult neck metastases independently. The END group had better 10-year LRC than the observation group (56% vs. 43%, p=0.002) and also better 10-year DMS than the observation group (43% vs. 32%, p

Abstract The adjustable conductance of a two‐terminal memristor in a crossbar array can facilitate vector‐matrix multiplication in one step, making the memristor a promising synapse for efficiently implementing neuromorphic computing. To achieve controllable and gradual switching of multi‐level conductance, important for neuromorphic computing, a theoretical design of a superlattice‐like (SLL) structure switching layer for the multi‐level memristor is proposed and validated, refining the growth of conductive filaments (CFs) and preventing CFs from the abrupt formation and rupture. Ti/(HfOx/AlOy)SLL/TiN memristors are shown with transmission electron microscopy , X‐ray photoelectron spectroscopy , and ab initio calculation findings corroborate the SLL structure of HfOx/AlOy film. The optimized SLL memristor achieves outstanding conductance modulation performance with linearly synaptic weight update (nonlinear factor α = 1.06), and the convolutional neural network based on the SLL memristive synapse improves the handwritten digit recognition accuracy to 94.95%. Meanwhile, this improved synaptic device has a fast operating speed (30 ns), a long data retention time (≥ 104 s at 85 ℃), scalability, and CMOS process compatibility. Finally, its physical nature is explored and the CF evolution process is characterized using nudged elastic band calculations and the conduction mechanism fitting. In this work, as an example the HfOx/AlOy SLL memristor provides a design viewpoint and optimization strategy for neuromorphic computing.

ObjectivesTo explore the possible risk factors of orocutaneous fistula (OCF) development in free flap reconstruction of the tongue/floor of the mouth (TFOM).MethodsData of patients who underwent free flap reconstruction of the TFOM were retrospectively analyzed. The association between clinicopathologic variables and OCF occurrence was analyzed using univariate and multivariate analyses.ResultsAltogether, 469 patients were enrolled. OCF occurred in 43 patients with a rate of 9.2%. The univariate analysis revealed the negative effects of smoking, preoperative albumin level, cachexia, T4 stage, neck dissection, entire resection of the floor of the mouth (FOM), segmental mandibulectomy, and surgical site infection on OCF occurrence. The multivariate analysis confirmed the independence of cachexia (p

Abstract Background Osteosarcoma is an aggressive malignant tumor which has attracted worldwide attention. MEX3A may be associated with tumors while has not yet seen its coverage on osteosarcoma. Herein, this study was to investigate the correlation between MEX3A and the progression of osteosarcoma. Methods Firstly, we determined that expression of MEX3A was significantly higher in osteosarcoma tissues than that in marginal bone by immunohistochemical staining. Additionally, MEX3A expression was downregulated by the RNAi‐mediated knockdown. The functions of MEX3A knockdown on proliferation, apoptosis, cell cycle, migration was assessed by MTT assay, flow cytometry, wound-healing assay and Transwell assay, respectively. Knockdown of MEX3A resulted in suppressing cell proliferation, increasing cell apoptosis, inducing the G2 phase cell cycle arrest, and attenuating cellular migration. Furthermore, mouse xenograft model confirmed inhibitory effects of MEX3A knockdown on osteosarcoma formation. Results The preliminary exploration on the molecular mechanism of MEX3A in osteosarcoma cells showed that the induction of apoptosis needs the participation of a series of apoptosis- associated factors, such as upregulation of Caspase 3, Caspase 8 and HSP60, downregulation of HSP27 and XIAP. Conclusions In summary, these findings predicated that therapy directed at decreasing MEX3A expression is a potential osteosarcoma treatment.

ObjectiveThe aim of this study is to identify the risk factors associated with orocutaneous fistula (OCF) formation after free flap reconstruction for oral squamous cell carcinoma (SCC).MethodsPatients undergoing free flap reconstruction for oral SCC were retrospectively enrolled. The relationship between clinicopathologic variables and OCF formation was analyzed by univariate and multivariate analyses.ResultsA total of 87 OCFs occurred in 856 patients. Univariate analysis revealed cachexia, tumor at the tongue/floor of the mouth (TFOM), T4 stage, preoperative hemoglobin level, pull-through procedure, preoperative albumin level, and surgical site infection were associated with the formation of OCF. Multivariate analysis confirmed the independence of cachexia, TFOM, T4 stage, and surgical site infection in predicting OCF development. Conventional wound care could achieve successful fistula closure in 82.4% of the patients with a median time of 28 days.ConclusionsOCF formation was common after free flap reconstruction. The presence of cachexia, TFOM tumor site, T4 stage, and surgical site infection significantly increased the risk of OCF formation. Although it required a long period, conventional wound care can obtain satisfactory outcomes in OCF management.

The adventitious rooting−related oxygenase (ARRO−1) gene is specifically expressed in the early rooting stage and is considered a molecular marker of rooting. In this study, a PsARRO−1 gene (GenBank accession number KJ620008) was identified from a pre−constructed transcriptome database of root development of Paeonia suffruticosa under sandy loam cultivation. The expression was verified by RT−qPCR, and it was found that the expression trend was consistent with the expression in the transcriptome database. The PsARRO−1 gene was specifically highly expressed during the root primordium germination phase. In addition, the RT−qPCR analysis indicated that the expression of PsARRO−1 in roots was significantly higher than in stems and leaves, its peak expression in vitro was 5 days earlier than in soil, and its expression was higher than that of tree peony in soil. Subcellular localization analysis showed that PsARRO−1 was localized in the plasma membrane. Moreover, the transient silent expression of the PsARRO−1 gene was found in the roots of peony seedlings grown using VIGS technology. The root activity was significantly reduced after transient silencing of the expression of the PsARRO−1 gene. These results indicate that PsARRO−1 has a positive regulatory effect on tree peony root development.

Various genomic variants were linked to inherited peripheral neuropathies (IPNs), including large duplication/deletion and repeat expansion, making genetic diagnosis challenging. This large case series aimed to identify the genetic characteristics of Japanese patients with IPNs. We collected data on 2695 IPN cases throughout Japan, in which PMP22 copy number variation (CNV) was pre-excluded. Genetic analyses were performed using DNA microarrays, next-generation sequencing-based gene panel sequencing, whole-exome sequencing, CNV analysis, and RFC1 repeat expansion analysis. The overall diagnostic rate and the genetic spectrum of patients were summarized. We identified 909 cases with suspected IPNs, pathogenic or likely pathogenic variants. The most common causative genes were MFN2, GJB1, MPZ, and MME. MFN2 was the most common cause for early-onset patients, whereas GJB1 and MPZ were the leading causes of middle-onset and late-onset patients, respectively. Meanwhile, GJB1 and MFN2 were leading causes for demyelinating and axonal subtypes, respectively. Additionally, we identified CNVs in MPZ and GJB1 genes and RFC1 repeat expansions. Comprehensive genetic analyses explicitly demonstrated the genetic basis of our IPN case series. A further understanding of the clinical characteristics of IPN and genetic spectrum would assist in developing efficient genetic testing strategies and facilitate early diagnosis.

Objective: The neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with survival in solid malignancies. The main goal was to evaluate the prognostic significance of the NLR in patients with p16-negative squamous cell carcinoma of unknown primary (SCCUP) in head and neck.Methods: The association between the NLR and clinical pathologic variables was evaluated by the chi-square test. The primary endpoint of interest was disease-specific survival (DSS). Univariate and Coxmodel analyses were used to evaluate prognostic factors.Results: A total of 153 patients were included in the analysis. Cancer cachexia was noted in 10 patients. The mean NLR value was 3.9 (range: 1.4–8.3). A high NLR was significantly associated with cancer cachexia development. The 5-year DSS rate was 58%. In patients with NLRs varying from 1.4 to 3.7, the 5-year DSS rate was 71%; in patients with NLRs varying from 3.7 to 6.0, the 5-year DSS rate was 57%; in patients with NLRs varying from 6.0 to 8.3, the 5-year DSS rate was 39%, and the difference was significant (p = 0.001). Further Cox model analysis confirmed the independence of the NLR in predicting survival.Conclusions: In patients with p16-negative SCCUP, an NLR ≥ 6.0 is significantly associated with worse prognosis.

Neonatal sepsis is a major global health challenge, leading to significant morbidity and mortality in newborns. The search for precise biomarkers for its early prediction in clinical settings has been ongoing, with heparin-binding protein (HBP) emerging as a promising candidate. Originating from granules in neutrophils, HBP is released into the bloodstream in response to infection and plays a pivotal role in the body's inflammatory response. Its significance extends beyond its inflammatory origins; research indicates dynamic changes in HBP levels are strongly linked to reduce in-hospital mortality, offering a prognostic advantage over existing biomarkers. Furthermore, HBP has demonstrated considerable clinical utility in the early diagnosis and stratification of neonatal sepsis, suggesting its potential as a reliable blood marker for early prediction of the disease and its severity. Its application may extend to guiding the judicious use of antibiotics in treating newborns, addressing a critical aspect of neonatal care. Despite these encouraging results, the precise clinical utility of HBP for diagnosing and treating sepsis in neonates still demands further clarification through extensive research. This review delves into the current scientific understanding of HBP's contribution to diagnosing, prognosticating, and treating neonatal sepsis, while considering its future clinical applications. [ABSTRACT FROM AUTHOR]

Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT. We also found that all four patients had characteristic neurological features of peripheral neuropathy and ataxia with cerebellar atrophy, and some patients showed leukoencephalopathy or spinal cord atrophy on MRI scans. Validated mutations were located at highly conserved residues among different species and segregated with the disease in each family. Nerve conduction studies showed axonal sensorimotor neuropathy. Sural nerve biopsies showed chronic axonal degeneration with a marked loss of large and medium myelinated fibres. An immunohistochemical assay with an anti-COA7 antibody in the sural nerve from the control patient showed the positive expression of COA7 in the cytoplasm of Schwann cells. We also observed mildly elevated serum creatine kinase levels in all patients and the presence of a few ragged-red fibres and some cytochrome c oxidase-negative fibres in a muscle biopsy obtained from one patient, which was suggestive of subclinical mitochondrial myopathy. Mitochondrial respiratory chain enzyme assay in skin fibroblasts from the three patients showed a definitive decrease in complex I or complex IV. Immunocytochemical analysis of subcellular localization in HeLa cells indicated that mutant COA7 proteins as well as wild-type COA7 were localized in mitochondria, which suggests that mutant COA7 does not affect the mitochondrial recruitment and may affect the stability or localization of COA7 interaction partners in the mitochondria. In addition, Drosophila COA7 (dCOA7) knockdown models showed rough eye phenotype, reduced lifespan, impaired locomotive ability and shortened synaptic branches of motor neurons. Our results suggest that loss-of-function COA7 mutation is responsible for the phenotype of the presented patients, and this new entity of disease would be referred to as spinocerebellar ataxia with axonal neuropathy type 3. [ABSTRACT FROM AUTHOR]

Objective: To analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from pediatric patients in a Chinese hospital. Methods: From October 2011 to May 2014, we collected 284 isolates (including 217 noninvasive and 67 invasive strains). We tested the antimicrobial susceptibility of these specimens using the Epsilomer test and disk diffusion method, and the expression of macrolide resistant genes ermB and mefA by polymerase chain reaction. Results: The most common serotype for 217 noninvasive strains was 19F (31.3%). The coverage rates of the 7-, 10-, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) were 53.9%, 53.9%, and 86.2%, respectively. For 67 invasive strains, the most common serotype was 23F (22.4%). The coverage rates of PCV7, PCV10, and PCV13 for invasive strains were 77.6%, 82.1%, and 91.0%, respectively. The susceptibility of strains isolated from nonmeningitis specimens to penicillin (PEN) was 97.2%. The rate of multidrug resistance in 284 isolates was 98.7%. All of these isolates were resistant to erythromycin (ERY) and had the ermB gene; 38.6% of those isolates had the mefA gene. Conclusions: Compared with PCV7 and PCV10, the coverage rate of PCV13 was relatively higher for the S. pneumoniae isolates from pediatric patients. This finding suggests that PCV13 probably plays the strongest role in prevention of pneumococcal diseases and control of multidrug resistance. Because pneumococci were sensitive to PEN, this drug is still the preferred choice for clinical treatment of pediatric pneumococcal diseases. [ABSTRACT FROM AUTHOR]

Background: Hereditary sensory and autonomic neuropathy (HSAN) type II with WNK1/HSN2 gene mutation is a rare disease characterized by early-onset demyelination sensory loss and skin ulceration. To the best of our knowledge, no cases of an autonomic disorder have been reported clearly in a patient with WNK/HSN2 gene mutation and only one case of a Japanese patient with the WNK/HSN2 gene mutation of HSAN type II was previously reported. Case presentation: Here we describe a 54-year-old woman who had an early childhood onset of insensitivity to pain; superficial, vibration, and proprioception sensation disturbances; and several symptoms of autonomic failure (e.g., orthostatic hypotension, fluctuation in body temperature, and lack of urge to defecate). Genetic analyses revealed compound homozygous mutations in the WNK1/HSN2 gene (c.3237_3238insT; p.Asp1080fsX1). The patient demonstrated sensory loss in the "stocking and glove distribution" but could perceive visceral pain, such as menstrual or gastroenteritis pain. She experienced frequent fainting episodes. She had undergone exenteration of the left metatarsal because of metatarsal osteomyelitis at 18 years. Sural nerve biopsy revealed a severe loss of myelinated and unmyelinated nerves. She complained of severe pain in multiple joints, even on having pain impairment. Although non-steroidal anti-inflammatory drugs are generally more effective than acetaminophen for arthritis, in our case, they were ineffective and acetaminophen (2400 mg/day) adequately controlled her pain and improved quality of life. Over 3 months, the numerical rating scale, pain interference scale of the Brief Pain Inventory, and the Pain Catastrophizing Scale decreased from 6/10 to 3/10, from 52/70 to 20/70, and from 22/52 to 3/52 points, respectively. Conclusions: This is the second reported case of a Japanese patient with WNK/HSN2 gene mutation of HSAN type II and the first reported case of an autonomic disorder in a patient with the WNK/HSN2 gene mutation. Acetaminophen adequately controlled arthropathy related pain in a patient with congenital impairment of pain sensation. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical significance of 3-phosphoinositide-dependent protein kinase-1 (PDK1) expression in hepatocellular carcinoma (HCC) and its association with clinicopathologic features and prognosis in HCC patients. Materials and methods: A total of 128 HCC patients who received radical resection were enrolled from Wenling Maternal and Child Health Care Hospital between May 2005 and December 2008, and tumor and adjacent tissue samples were collected. Expression of PDK1 was detected by immunohistochemistry method. Correlation of PDK1 expression with clinicopathological features and prognosis was determined by Spearman's correlation analysis. Impact of expression of PDK1 on overall survival and recurrence was determined by Kaplan-Meier analysis. Results: Immunohistochemistry results showed that PDK1 expression in HCC tissues was significantly higher than that in the corresponding adjacent cancer tissues. Univariate analysis showed that PDK1 messenger RNA expression can predict time to recurrence with diagnostic significance (P=0.001). Univariate analysis showed that alpha-fetoprotein level, tumor number, tumor encapsulation, microvascular invasion, and tumor-node-metastasis stage were also unfavorable prognostic variables for recurrence (P<0.05). Kaplan-Meier analysis showed that overexpression of PDK1 correlates with significantly shorter postoperative overall survival and higher recurrence rates (hazard ratio =2.68; 95% confidence interval: 2.46-4.42, P=0.001) in HCC patients after curative resection. Conclusion: Our study indicated that PDK1 may serve as a candidate pro-oncogene and a potential prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

To investigate the effects of signal transducer and activator of transcription 3 (STAT3) combined with cisplatin (CDDP) on the growth of human Wilms tumour (WT) SK-NEP-1 cell subcutaneous xenografts in nude mice and the possible mechanisms. Human WT SK-NEP-1 cells were subcutaneously transplanted to establish the BALB/c nude mice xenograft model. Mice were randomly divided into five groups: blank control group, adenovirus control group (NC group), STAT3 group, CDDP group and STAT3 plus CDDP group (combination group). Tumour volume and tumour weight were observed during the therapeutic process. The expression levels of STAT3, glucose regulatory protein 78 (GRP78) and BCL2-associated X protein (BAX) were evaluated by immunohistochemical analysis. Compared with the STAT3 group or CDDP group, the tumour weight and volume was significantly reduced in the combination group (P<0.05). No statistical significance was found in NC group compared with the blank control group (P>0.05). Immunohistochemical analysis showed that STAT3, GRP78 and BAX protein levels in the combination group were significantly higher than those in STAT3 group and CDDP group (P<0.05). Exogenous STAT3 and CDDP may synergistically inhibit the xenograft tumour growth through up-regulation of BAX protein via GRP78. [ABSTRACT FROM AUTHOR]