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Objectives To explore the prognostic factors of patients with low-grade optic pathway glioma (OPG) and the optimal treatment to reduce the incidence of postoperative hydrocephalus. Patients and methods This single-center study retrospectively analyzed data from 66 patients with OPGs who underwent surgery. The patients were followed, and overall survival (OS) and progression-free survival (PFS) were determined. The effects of different treatments on the hydrocephalus of patients were compared. Results Postoperative hydrocephalus was identified as a factor to increase the risk of mortality by 1.99-fold (p = .028). And, 5-year survival rate was significantly lower among patients with postoperative hydrocephalus (p = .027). The main factors leading to preoperative hydrocephalus in patients are large tumor volume and invasion into the third ventricle. Gross total resections (GTR) could reduce the risk of long-term hydrocephalus (p = .046). Age younger than 4 years (p = .046) and tumor invasion range/classification (p = .029) are the main factors to reduce the five-year survival rate. Postoperative radiotherapy (RT) and chemotherapy (CT) had no significant effects on OS. Extraventricular drainage (EVD) was not associated with perioperative infection (p = .798 > .05) and bleeding (p = .09 > .05). Compared with 2 stage surgery (external ventricular drainage or ventriculoperitoneal shunt (VPS) was first placed, followed by tumor resection), 1 stage surgery (direct resection of tumor) had no complication increase. Conclusions Postoperative hydrocephalus is mostly obstructive hydrocephalus, and it is an important factor that reduces the OS of patients with low-grade OPGs. Surgery to remove the tumor to the greatest extent improves cerebrospinal fluid circulation is effective at reducing the incidence postoperative hydrocephalus. For patients whose ventricles are still dilated after surgery, in addition to considering poor ventricular compliance, they need to be aware of the persistence and progression of hydrocephalus.

Purpose This study aimed to explore the relationship between the aggressiveness and immune cell infiltration in pituitary adenoma (PA) and provide the basis for immuno-targeting therapies. Methods One hundred three patients with PA who underwent surgery at a single institution were retrospectively identified. The infiltration of macrophages and T-lymphocytes was quantitatively assessed. Results The number of CD68 + macrophages was positively correlated with Knosp (P = 0.003) and MMP-9 expression grades (P = 0.00). The infiltration of CD163 + macrophages differed among Knosp (P = 0.022) and MMP-9 grades (P = 0.04). CD8 + tumor-infiltrating lymphocytes (TILs) were also positively associated with Knosp (P = 0.002) and MMP-9 grades (P = 0.01). Interestingly, MGMT expression was positively correlated with MMP-9 staining extent (P = 0.000). The quantities of CD8 + TILs (P = 0.016), CD68 + macrophages (P = 0.000), and CD163 + macrophages (P = 0.043) were negatively associated with MGMT expression levels. The number of CD68 + macrophages in the PD-L1 negative group was significantly more than that in the PD-L1 positive group (P = 0.01). The rate of PD-L1 positivity was positively correlated with the Ki-67 index (P = 0.046) and p53 expression (P = 0.029). Conclusion Targeted therapy for macrophages and CD8 + TILs could be a helpful treatment in the future for aggressive PA. Temozolomide (TMZ) may have better effects on the treatment of PAs with greater immune cell infiltration. Anti-PD-L1 therapy may better respond to PAs with higher Ki-67 and p53 expression and more infiltrating CD68 + macrophages. Multiple treatment modalities, especially combined immunotherapy, or combination immunotherapy with TMZ, could become a novel therapeutic strategy for aggressive PA.

A novel printed monopole antenna with simple, low-profile and convenient design is presented in this paper. The antenna composes of a printed monopole antenna and a folded-line stepped impedance re...

DNA base editors have been harnessed as an exciting therapeutic platform for human diseases and are rapidly progressing into human clinical trials. However, persistent expression of base editors delivered via adeno-associated virus (AAV) poses concerns with specificity and immunogenicity. Here we develop self-inactivating base editor (siBE) systems with a negative feedback loop where one guide RNA (gRNA) targets the gene of interest and the other targets the deaminase domain itself. We demonstrate that siBE confers efficient on-target editing with time-dependent self-inactivation and increased editing specificity. For the in vivo utilization, we further employ the intein split approach to package siBE targeting mouse Angptl3 into AAV9. Systemic delivery of AAV9-siBE confer efficient editing of Angptl3 in liver, resulting in reduced serum levels of ANGPTL3, triglyceride and total cholesterol, with the active base editor undetectable at 8 weeks after administration. These self-inactivating base editing systems are highly promising for future therapeutic applications.

Background Neonatal thrombocytopenia is common in preterm and term neonates admitted to neonatal intensive care units. The etiology behind neonatal thrombocytopenia is complex. Inherited thrombocytopenia is rare and usually results from genetic mutations. Case presentation Here we report a case of twins with severe inherited thrombocytopenia presented in the neonatal period who were shown to be compound heterozygotes for 2 UDP-N-acetylglucosamine 2-epimerase (GNE) gene mutations, c.1351C > T and c.1330G > T, of which c.1330G > T is a novel mutation. Conclusion These two GNE mutations may help in the diagnosis and management of thrombocytopenia diagnosed in neonates.

Background:Kawasaki disease is a type of acute febrile rash disease that is common in children and is characterised by primary lesions of systemic middle and small vasculitis, which can lead to coronary artery lesions. Manganese superoxide dismutase (MnSOD), one of the most important antioxidases in the human body, plays a key role in maintaining the balance of free radicals in the human body. Two single-nucleotide polymorphisms (SNPS) (rs4880 and rs5746136) in the MnSOD gene were related to oxidative stress disease. The purpose of this study is to explore the possible relationship between MnSOD gene polymorphisms and Kawasaki disease susceptibility.Methods:This study included 100 Kawasaki disease children and 102 healthy children. Two single-nucleotide polymorphisms (rs4880 and rs5746136) were detected by polymerase chain reaction sequence-based typing.Results:There was a significant difference in both the genotype frequency (χ2 = 10.805, p = 0.005) and the allele frequency (χ2 = 7.948, p = 0.005) of rs5746136 between the Kawasaki disease group and the control group. Children with the A allele had a 0.558 times lower risk of Kawasaki disease than those without the A allele (χ2 = 7.948, p = 0.005, odds ratio = 0.558, 95% confidence interval = 0.371–0.838). There was no significant difference in the genotype and gene frequencies of rs5746136 between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesion groups (p > 0.05), and there was no significant difference in the rs4880 genotype and allele frequencies between the Kawasaki disease and healthy control groups or between the Kawasaki disease-coronary artery lesion and Kawasaki disease-without coronary artery lesions groups (p > 0.05).Conclusion:This study provides evidence supporting an association between MnSOD gene polymorphisms and susceptibility to Kawasaki disease. The genotype AA and the allele A of the MnSOD gene locus rs5746136 were risk factors for Kawasaki disease.

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Cyclophilin A (CypA), also known as PPIA, has been identified to play a vital role in the pathogenesis of card...

Severe neonatal episodic laryngospasm (SNEL) is an ion channel disease characterized by recurrent life-threatening myotonia of respiratory muscle due to mutations in the voltage-gated sodium channel genes. Here we reported a newborn manifested as paroxysmal cyanosis and limb myotonia after birth. The neonate also developed muscle hypertrophy and stunted growth during the follow-up. Whole exome sequencing confirmed c.2395GA, p.Ala799Thr heterozygous mutation of SCN4A严重新生儿发作性喉痉挛(severe neonatal episodic laryngospasm，SNEL)是一种离子通道病，该病因钠电压门控通道4亚基(sodium voltage-gated channel alpha subunit 4 gene，SCN4A)基因突变导致反复发作性咽喉肌强直而危及新生儿生命。现报告1例在出生后出现阵发性发绀和四肢强直的新生儿病例，随访期间，患儿还出现四肢肌肥大和生长发育迟缓。全外显子测序证实该患儿存在SCN4A基因新型杂合突变(c.2395GA, p.Ala799Thr)。卡马西平是治疗该病的有效药物。此病例扩展了我们对SCN4A基因突变表型的认识。总结已报道的16例SNEL病例特点，发现他们主要发生p.G1306E位点错义突变。相似症状表现为新生儿期上气道肌紧张和喂养困难，长大后多数患者表现为不同程度的发作性肌强直和进行性的肌肥大。一些患者出现“运动员”特征外貌，但几乎所有患者肌电图均有肌强直放电。.

Background The classification and treatment strategy of atypical central neurocytomas (CNs) are still controversial largely, this study aimed to explore the optical treatment strategy and characteristics in transcriptomic profile. Methods This study retrospectively analyzed data from Sixty-one patients with CNs who underwent surgery in single institution. Whole-transcriptome analysis was used to investigate the differences between typical and atypical CNs. Results The five-year OS (P= 0.015) and PFS rates (P= 0.000002) were significantly higher in the complete resection group than in the incomplete resection group. Postoperative radiotherapy did not affect OS (P=0.255) or PFS (P=0.398) in the complete resection group. The five-year PFS rate (P=0.000038) among patients in the complete resection group who did not receive radiotherapy was significantly longer than that among patients in the incomplete resection group who received radiotherapy. The extent of surgical resection and operative approaches were irrelevant to perioperative complications and dsyfunctions at the last follow-up. Compared with caudate control, some of differentially expressed genes may involve cancer. Finally, the overexpression of ten genes (AMOTL1, PIK3R3, TGFBR1, SMO, COL4A6, MGP, SOX4, IGF2, Slit1 and CKS2) in atypical CNs may be associated with malignancy in atypical CNs. Conclusion Complete resection is relatively the best therapeutic modality for atypical CNs, radiotherapy is not necessary for patients after complete resection of the tumor. Although the previous definition of atypical CNs may not have significant prognostic value, the overexpression of ten genes may be involved in malignant behaviors and potential candidate hallmarks for differentiating the atypical CNs. Although the number of cases was relatively small, the findings could be helpful and instructive in the clinical treatment of this disease.

BACKGROUND: Uric acid was once considered an effective endogenous antioxidant, but now more and more evidence shows that it may play a significant role in the pathophysiology of cardiovascular diseases.OBJECTIVES: It has not been clear that UA is a sign of poor prognosis or a risk factor for CVD. Our aim is to figure out the exact relationship between CVD and uric acid. METHODS: We studied 3356 publications in the past 44 years through MEDLINE, EMBASE, and Cochrane library searches, and selected 22 studies that met our inclusion criteria. RESULTS: The meta-analysis showed that hyperuricemia was associated with an increased risk of death from CVD (RR=1.37; 95% CI:1.29-1.45; I2=31.4%, P=0.157). Sensitivity analysis reviewed several potential sources of heterogeneity between studies, such as average SUA level, study location, and outcome indicators.

Background Mutations in the ADAMTS13 gene can lead to an ADAMTS13 enzyme deficiency, which is related to Upshaw–Schulman syndrome (USS). USS is a common type of thrombotic thrombocytopenic purpura (TTP). Here we present a very rare case of TTP caused by 2 mutations in the ADAMTS13 gene. Besides, we reviewed and summarized previous pathogenic ADAMTS13 gene mutations associated with the TTP. Case presentation A 10-year-old female was admitted to the Third Xiangya Hospital of Central South University after experiencing discontinuous thrombocytopenia for 8 years, abnormal renal function for more than 2 years, cough for more than 10 days, and weakness of the left limb for 3 days. Gene sequencing shows the patient’s ADAMTS13 gene contains compound heterozygous nucleotide variations: c.1335delC (p. Phe445LeufsTer52) is a frameshift variation inherited from her father and c.2130C > G (p. Cys710Trp) is a missense variation inherited from her mother. The final diagnosis was USS. Conclusions Our study reports a very rare genetic TTP case caused by two compound heterozygous variants in the ADAMTS13 gene. The effect of these two mutations on the secretion of ADAMTS13 requires further in vitro experiments to confirm.

Viral myocarditis is potentially fatal and lacking a specific treatment. Exosomes secreted by cardiac progenitor cells (CPCs) have emerged as a promising tool for cardioprotection and repair. In this study, we investigated whether CPCs-derived exosomes (CPCs-Ex) could utilize the mTOR signal pathway to reduce the apoptosis in viral myocarditis. In vitro, exosomes were, respectively, added to H9C2 cells after CVB3 infection to detect the anti-apoptosis effect of CPCs-Ex. Compared with the controls, the apoptosis rate was reduced, accompanied with the depressed expression of viral capsid protein 1 (VP1) and pro-apoptosis factors of Bim/caspase families. Meanwhile, the phosphorylation of Akt, mTOR, and p70S6K were promoted, but that of 4EBP1 was suppressed. In vivo, the results of apoptosis, expression of CVB3 and pro-apoptosis factors, and phosphorylation of Akt/mTOR factors of CVB3-infected cardiomyocytes were consistent with that of vitro. Following that, we use Rapamycin and MK-2206 to inhibit the Akt/mTOR signaling pathway, meanwhile, Rattus 4EBP1, p70S6K, Akt1 and Akt2 were transfected to H9C2 cells to establish the stably transfected cell lines. In the group with Rapamycin or MK-2206 pretreatment, CPCs-Ex also could decrease the apoptosis of H9C2 cells and expression of CVB3 mRNA, followed by decreased expression of apoptosis factors. In Akt2, p70S6K and 4EBP1 overexpression groups, CPCs-Ex promoted CVB3-induced apoptosis, VP1 expression and cleavage of caspase-3. Our results therefore identify CPCs-Ex exerts an anti-apoptosis effect in CVB3-infected cells by abrogating the proliferation of CVB3 and modulating the mTOR signaling pathways as well as the expression of Bcl-2 and caspase families. Viral myocarditis, mainly caused by CVB3 infection, is lacking a specific treatment. Our study identified an anti-apoptosis role of CPCs-Ex in CVB3-infected cells and rats, which shown that CPCs-Ex may be an effective tool to treat viral myocarditis. We believe that with more in-depth research on the functionality of CPCs-Ex, there will be a breakthrough in the treatment of viral myocarditis.

A case of SNX10 gene mutation in a patient with infantile malignant osteopetrosis (IMO) was admitted to Department of Pediatrics, Third Xiangya Hospital, Central South University. The patient had the symptom of anemia, hepatosplenomegaly and growth retardation. The X-ray examination suggested extensive increase of bone density throughout the body, which was clinically diagnosed as IMO. The homozygous mutation of SNX10 gene c.61CT was found via gene sequencing. We reviewed the relevant literatures and found that anemia, visual and hearing impairment, hepatosplenomegaly are the main clinical symptoms of IMO, SNX10 gene mutation is a rare cause of IMO, and hematopoietic stem cell transplantation is an effective treatment.中南大学湘雅三医院儿科收治1例SNX10基因突变致婴儿恶性石骨症(infantile malignant osteopetrosis，IMO)患儿。该患儿临床表现为贫血、肝脾肿大、生长发育迟缓，X线检查提示全身骨密度广泛增高，临床诊断为IMO。基因测序为SNX10基因c.61CT纯合突变。通过对国内外相关文献进行复习，发现贫血、视听力障碍、肝脾肿大是IMO的主要临床症状，SNX10基因突变是导致IMO的罕见原因，造血干细胞移植是其有效的治疗手段。.

BackgroundTemozolomide can be used in the treatment of pituitary adenoma. Its efficacy can be evaluated by the expression of 06-methylguanine-DNA methyltransferase (MGMT). However, the previous study population was mainly adult. This study was the first to evaluate the expression of MGMT in children and adolescents with pituitary adenomas.MethodsThe clinical features and biological characteristics of 38 cases of pituitary adenoma in children and adolescents were analyzed retrospectively. The expression of MGMT, Ki-67, p53 was marked by immunohistochemical staining.ResultsIn this cohort, the expression of MGMT protein is 16/38 (42.11%). The low expression rate of MGMT in children and adolescent somatotroph adenomas was only 11.11%, which was much lower than that of adults. Ki-67 expression range of 1% -10%（mean 4.24 ± 2.71%）. The positive rate of p53 was 22/38 (57.89%). The statistical analysis showed that the expression of MGMT was related to the diameter of the tumor (P=0.01), the diameter of the tumor was large, and the expression of MGMT was high. The expression of MGMT was not associated with age, sex, tumor type, invasiveness, texture, apoplexy, recurrence, and expression of p53 and Ki-67.ConclusionSomatotroph adenomas, large-diameter children and adolescent pituitary adenomas may be not suitable for temozolomide treatment. To determine whether temozolomide responds to salvage therapy in children and adolescents with pituitary adenomas, MGMT expression should be assessed in all pituitary adenomas, the time span between specimen collection and temozolomide treatment needs to be considered because of the instability of MGMT protein expression.

Objective: Central neurocytomas (CNs) are rare, and this has resulted in a paucity of information and a lack of clarity regarding their optimal management. This study aimed to explore individual treatment strategies for CNs and the benefits of these strategies for patients. Methods: This single-center study retrospectively analyzed data from 67 patients with CNs who underwent surgery. Based on the extent of resection, patients were divided into complete and incomplete resection groups. The patients were followed, and overall survival (OS) and progression-free survival (PFS) were determined. Results: Of 55 patients (82.1%) who underwent complete resections, 24 received radiotherapy (24/55, 43.6%). Of 12 patients who underwent incomplete resections, 9 (9/12, 75.0%) received radiotherapy. The OS (p = 0.003) and PFS (p = 0.006) intervals were significantly longer in the complete resection group than in the incomplete resection group. Postoperative radiotherapy did not affect OS (p = 0.129) or PFS (p = 0.233) in the complete resection group. In the incomplete resection group, postoperative adjuvant radiotherapy prolonged patient survival significantly (p = 0.021). PFS was significantly longer among patients who underwent complete resection without radiotherapy than in those who underwent incomplete resection followed by radiotherapy (p = 0.034). Functional dependence on admission, which was defined as a Karnofsky Performance Status score

Background Kawasaki disease (KD) is an acute febrile illness of early childhood. The exact etiology of the disease remains unknown. At present, research on KD is mostly limited to susceptibility genes, infections, and immunity. However, research on the correlation between gut microbiota and KD is rare. Methods Children with a diagnosis of acute KD and children undergoing physical examination during the same period were included. At the time of admission, the subjects’ peripheral venous blood and feces were collected. Faecal samples were analyzed for bacterial taxonomic content via high-throughput sequencing. The abundance, diversity, composition, and characteristic differences of the gut microbiota in KD and healthy children were compared by alpha diversity, beta diversity, linear discriminant analysis and LDA effect size analysis. Blood samples were used for routine blood examination, biochemical analysis, and immunoglobulin quantitative detection. Results Compared with the control group, the community richness and structure of gut microbiota in the KD group was significantly reduced (Chao1 richness estimator, mean 215.85 in KD vs. mean 725.76 in control, p < 0.01; Shannon diversity index, mean 3.32 in KD vs. mean 5.69 in control, p < 0.05). LEfSe analysis identified two strains of bacteria significantly associated with KD: Bacteroidetes and Dorea. Bacteroidetes were enriched in healthy children (mean 0.16 in KD vs. mean 0.34 in control, p < 0.05). Dorea was also enriched in healthy children but rarely existed in children with KD (mean 0.002 in KD vs. mean 0.016 in control, p < 0.05). Compared with the control, IgA and IgG in the KD group decreased (IgA, median 0.68 g/L in KD vs. median 1.06 g/L in control, p < 0.001; IgG, median 6.67 g/L in KD vs. median 9.71 g/L in control, p < 0.001), and IgE and IgM levels were not significantly changed. Conclusions Dysbiosis of gut microbiota occurs in children with acute KD and may be related to the etiology or pathogenesis of KD. It is worth noting that for the first time, we found that Dorea, a hydrogen-producing bacterium, was significantly reduced in children with acute KD. Overall, our results provide a theoretical basis for the prevention or diagnosis of KD based on intestinal microecology.

To investigate the genetic association of miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C in patients with Kawasaki disease (KD) and coronary artery lesions (CAL). There were 120 patients with KD and 126 healthy subjects in this study. The genotype of loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C of miR-146a gene were detected by polymerase chain reaction-sequence-based typing. For miR-146a gene polymorphisms at loci rs2910164 G/C, rs57095329 A/G, and rs6864584 T/C, there were no significant difference of genotype frequencies and allele frequencies between KD group and healthy control group, or between the IVIG-resistant group and IVIG-sensitive group (P > 0.05). In KD with coronary artery lesions (KD-CAL) group, the genotype frequencies of GG were higher than that in KD without coronary artery lesion (KD-WO) group at locus rs2910164 G/C polymorphisms of miR-146a gene (χ2 = 6.660, P = 0.036), patients with KD carried genotype of GG were at 3.636 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 6.455, P = 0.018, OR = 3.636, 95%CI = 1.280–10.262). While there was no significant difference of allele frequency of G and C between KD-CAL group and KD-WO group (P > 0.05). In KD-CAL group, the allele frequency of A was higher than that in KD-WO group at locus rs57095329 A/G polymorphisms of miR-146a gene (χ2 = 4.745, P = 0.035), carriers with allele A were at 2.422 times higher risk of getting coronary artery lesions than those of non-carriers (χ2 = 4.745, P = 0.035, OR = 2.422, 95%CI = 1.073–5.465), while there was no significant difference of genotype frequency of AA, AG, and GG types between KD-CAL group and KD-WO group (P > 0.05). There was no significant difference of genotype frequencies of TT, TC, and CC types and allele frequencies of T and C types between KD-CAL group and KD-WO group at locus rs6864584 T/C polymorphisms of miR-146a gene (P > 0.05). The significant association has been found between the genotype and allele frequency of the miR-146a gene loci rs2910164 G/C and rs57095329 A/G, the genotype GG of rs2910164 G/C, and allele A of rs57095329 A/G were risk factors for getting coronary artery lesions.

Exosomes are cell‑derived vesicles released from a variety of mammalian cells that are involved in cell‑to‑cell signalling. It has been reported that cardiac progenitor cells (CPCs) derived from an adult heart are one of the most promising stem cell types for cardioprotection and repair. The mammalian target of rapamycin (mTOR) signalling pathway is a pivotal regulator in CPCs, therefore, CPC‑derived exosomes were used in the present study to investigate whether it can promote H9C2 cell growth through the protein kinase B (PKB, or Akt)/mTOR signalling pathway. The CPCs were isolated from Sprague‑Dawley hearts. Following treatment with a specific medium, the exosomes were purified and identified by electron micrograph and western blot assays, using CD63 and CD81 as markers. The methyl‑thiazolyl‑tetrazolium and 5‑ethynyl‑2'‑deoxyuridine methods were used to detect H9C2 cell growth. The expression of Akt and mTOR were detected by western blot analysis following treatment with 200 or 400 µg/ml of exosomes for 24 or 48 h, respectively. It was found that, compared with higher concentrations of exosomes, prolonging the duration of exposure promoted cell growth. Accordingly, CPC‑derived exosomes stimulated the expression of Akt to a marked degree; groups treated with exosomes for 48 h showed higher expression of Akt than those treated for 24 h at the same concentration. mTOR was also stimulated by CPC‑derived exosomes. The activation of mTOR increased in accordance with the treatment time at an exosome concentration of 200 µg/ml and decreased with treatment time at an exosome concentration of 400 µg/ml. In conclusion, the present study demonstrated that CPC‑derived exosomes promoted H9C2 cell growth via the activation of Akt/mTOR in a time‑dependent manner at a relatively low exosome concentration, which may provide a novel therapy for cardiovascular disease.

Tourette syndrome (TS) is a complex neuropsychiatric disorder with chronic motor and vocal tics. Though the etiology is elusive, strong evidence for a genetic contribution to TS has been established. To date, various chromosomal or genetic alterations have been implicated in its pathogenesis. Recently, the deletion in the arylacetamide deacetylase gene (AADAC) was reported to be associated with TS. To investigate the association between the AADAC gene variants and TS, we conducted genetic analysis of the AADAC gene in 200 Han Chinese patients and 300 ethnicity-matched normal controls. Two variants, including a heterozygous splice-site variant, c.361 + 1G > A (rs762169706), and a missense variant, c.744A > T (p.R248S, rs186388618), were identified in two unrelated patients. The c.361 + 1G > A variant, absent in 300 ethnicity-matched controls, led to the deletion of exon 2 in AADAC mRNA, probably associated with development of TS. The c.744A > T variant, predicted to be damaging, was identified in two normal controls. The findings indicate that the AADAC gene c.361 + 1G > A variant may be a potential candidate factor for TS development, though further investigations are warranted.

Recent studies have found that viral myocarditis (VMC) associated with coxsackievirus B3 (CVB3) causes autophagy activation after infection, but the specific mechanism is not clear. The present study demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway participates in CVB3-induced autophagy. We found that the light chain 3 (LC3)-II/LC3-I ratio was increased and p62 and p-mTOR were altered at different times during CVB3 infection. To further assess the effects of this signaling pathway on CVB3 infection and viral replication, we selected 24 h post-inoculation (h.p.i.) as our research time point to conduct our next study. We inhibited the function of PI3K, Akt1 and mTOR. The outcome showed that inhibition of PI3K with ZSTK474 alleviated autophagy and decreased CVB3 mRNA replication and VP1 expression. Inhibition of mTOR with rapamycin promoted autophagy and viral mRNA replication but did not impact VP1 expression. Inhibition of Akt with MK2206 aggravated autophagy induced by viral infection. In our research, p62 exhibited a decrease at the beginning of infection but then increased as infection time increased. This finding may serve as a clue to elucidate the function of autophagy at different times of infection. However, the details merit further study. In conclusion, our findings suggest that the PI3K/Akt/mTOR signaling pathway participates in the process of autophagy induced by CVB3 infection. This finding may provide a new perspective of CVB3-induced autophagy.

The present study aimed to compare the thickness of brain abscesses in the deep and the superficial brain and to investigate the factors that influence the capsule of brain abscesses. The thickness of the brain abscess wall was evaluated on imaging. Bacteriological examination was performed on the abscess pus and wall, and immunohistochemical staining was used to count the number of macrophages. Kaplan-Meier curves were used to analyze overall survival. The results indicated that the wall of deep-brain abscesses was thicker than that of superficial abscesses. There was a difference in the extent of macrophage infiltration of deep- and superficial-brain abscess walls, and differences in the extent of macrophage infiltration in the wall of brain abscesses caused by various microorganisms were statistically significant. Of note, among the brain abscesses caused by Staphylococcus, the extent of macrophage/microglia infiltration and the thickness of the wall of the deep-brain abscesses were greater than those of superficial-brain abscesses and there was a positive correlation between the number of macrophages and the thickness of the abscess wall. The overall survival (OS) of patients with deep-brain abscess was not significantly shorter than that of patients with superficial-brain abscess. Furthermore, OS was not significantly different among groups of patients receiving different types of treatment. In conclusion, the wall of deep-brain abscesses is thicker than that of superficial abscesses and the infiltration of macrophages is abundant. The thick wall of abscesses in the deep brain may be associated with macrophage infiltration.

To investigate association between the single nucleotide polymorphisms of endothelial protein C receptor (EPCR) gene and the risk of Kawasaki disease (KD) in a Chinese children. Methods: A total of 103 KD patients including 23 patients with coronary artery lesions (CAL) and 158 controls were recruited. Seven tagging SNPs (rs6088738, rs2069940, rs2069945, rs2069952, rs867186, rs9574, and rs1415774) of EPCR gene were selected for TaqMan allelic discrimination assay. The plasma soluble EPCR (sEPCR) levels of 53 KD and 52 healthy children were detected by ELISA. Results: We found a significant association between rs2069952, rs9574 or rs1415774 and higher probability for the occurrence of KD but not CAL formation. Interestingly, males with these 3 SNPs and rs2069945 SNPs bore a much greater risk of KD than females. The level of plasma sEPCR in children with KD didnot predict the formation of CAL. However, the allele G of rs867186 in EPCR was associated with the increased level of plasma sEPCR in KD patients. Conclusion: The SNPs of EPCR are associated with KD susceptibility in a Chinese Han children.目的：调查中国儿童人群内皮细胞蛋白C受体(endothelial protein C receptor，EPCR)基因的单核苷酸多态性是否与川崎病(Kawasaki disease，KD)相关。方法：招募103名KD患者(其中23名患者出现冠状动脉病变)和158名对照组。选择EPCR基因的7个标记单核苷酸多态性(rs6088738，rs2069940，rs2069945，rs2069952，rs867186，rs9574和rs1415774)进行TaqMan等位基因鉴别分析。采用酶联免疫吸附试验(ELISA)检测53名KD和52名健康儿童血浆可溶性EPCR(soluble EPCR，sEPCR)水平。结果：rs2069952，rs9574，rs1415774与KD的发生显著相关，但与冠状动脉病变的发生无关。具有rs2069952，rs9574，rs1415774和rs2069945单核苷酸多态性的男性比女性具有更大的KD风险。KD患儿血浆sEPCR水平不能预测冠状动脉病变的形成，而KD患者rs867186等位基因G与血浆sEPCR水平升高有关。结论：中国汉族儿童EPCR的单核苷酸多态性与KD易感性有关。.

The aim of the present study was to explore the clinical characteristics of repeated hemorrhages of meningioma and analyze the causes of hemorrhage. Meningiomas are mostly benign tumors that rarely manifest hemorrhagic strokes. In the present study, a case of sphenoid ridge meningioma with repeated hemorrhages is reported. Internal hemorrhage was first observed, which, on further aggravation, formed a hematoma in the brain parenchyma and finally led to the development of a hernia. No neurological deficit was present after surgery and rehabilitation. A postoperative pathological examination showed increased levels of Ki-67, abnormal blood vessels in the tumors and the presence of progesterone, which indicate possible causes of the hemorrhage. A review of associated previous studies revealed that hemorrhages originate mainly from inside the meningioma. Two cases of meningiomas with repeated hemorrhages have been reported; one in the foramen magnum region and the other in the pineal gland area. The foramen magnum tumor had an interval of 1.33 months between two hemorrhagic episodes. Collecting relevant data from the latter case was not possible. In the present case report, the interval between two bleeding episodes was 3 days. The literature review also revealed that the average age of onset of meningioma is relatively young at only 28.00±6.24 years. In conclusion, repeated hemorrhages in meningiomas are extremely rare and the causes have not yet been identified. Increased Ki-67 and abnormally proliferating blood vessels may be potential causes of hemorrhage. Early diagnosis and rapid surgical intervention are essential to prevent further episodes of bleeding, which may otherwise have fatal consequences for the patients.

Familial renal glucosuria (FRG) is a rare condition that involves isolated glucosuria despite normal blood glucose levels. Mutations in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium-glucose cotransporter 2 (SGLT2), have been reported to be responsible for the disease. Genetic testing of the SLC5A2 gene was conducted in a Chinese family with FRG. A number of online tools were used to predict the potential effect of the identified mutations on SGLT2 function. Additionally, the SLC5A2 mutations previously reported in PubMed were summarized. A novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene in a Chinese child with FRG was identified. In total, 86 mutations of the SLC5A2 gene have been reported to be associated with FRG. The novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene may be responsible for the onset of FRG. The present study provides a starting point for further investigation of the molecular pathogenesis of the SLC5A2 gene mutation in patients with FRG.

Nesfatin-1 was identified as a satiety factor involved in the regulation of metabolism. Altered levels of circulating nesfatin-1 had been observed in a variety of diseases characterized by energy imbalance. However, there was no published data about nesfatin-1 levels in acromegaly. We evaluated serum nesfatin-1 levels in 13 patients with acromegaly at baseline and postoperatively, and in 21 age- and body mass index (BMI)-matched healthy subjects. Compared with the healthy subjects, patients with acromegaly had significantly increased levels of serum insulin, high-density lipoprotein cholesterol, triglyceride, and growth hormone (GH). Moreover, the acromegaly group had nesfatin-1 levels higher than controls (1.96 ± 0.56 ng/mL vs 0.61 ± 0.10 ng/mL, P = .004). There was a positive correlation of serum nesfatin-1 levels with diastolic blood pressure (r = 0.579, P = .038) and homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.598, P = .031) in patients with acromegaly. While a successful surgery decreased serum GH levels, the serum nesfatin-1 levels did not change in acromegaly (P = .965). At last, we compared serum GH/nesfatin-1 levels with predictive markers for aggressive behaviors in pituitary adenomas. There was no relationship between serum nesfatin-1 levels and tumor's size, Ki-67 index, mutant p53, or MGMT proteins. However, increased serum GH levels were positively correlated with tumors’ size (P = .023) and mutant p53 proteins expression (P = .028). Circulating nesfatin-1 was increased in acromegaly, which was involved in metabolism regulation.

Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects children, and it can result in coronary artery lesions. Cyclooxygenase-2 (COX-2) is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of several prostaglandins. The aim of this study was to examine the association between COX-2 gene polymorphisms and susceptibility to KD.A total of 276 subjects (136 KD and 140 controls) were recruited. The analysis of two single nucleotide polymorphisms rs689466 (-1195G/A) and rs20417 (-765G/C) was respectively detected with polymerase chain reaction sequence-based typing methods.Polymorphisms of rs689466 were significantly different between the normal controls and KD patients (χThis study provides the first evidence supporting an association between COX-2 gene polymorphisms and susceptibility of KD. The AA genotype and A allele of rs689466 confer predisposing factors to KD.

Coxsackievirus B3 (CVB3) infection has been shown to stimulate autophagy. We have demonstrated that the inhibition of phosphoinositide 3‑kinase (PI3K)/protein kinase B/mammalian target of rapamycin complex (mTORC) signaling pathway could affect the autophagic reaction induced by CVB3 infection in our previous study. However, the processes associating autophagy and CVB3 replication remain to be determined. In the present study, CVB3‑induced autophagy and its impact on viral replication were investigated. Rapamycin (inhibitor of mTOR) and ZSTK474 (inhibitor of PI3K) were used to change the autophagic reaction caused by CVB3 in Hela cells at different post‑infection (p.i.) time points (6, 9, 12 and 24 h p.i.), meanwhile, we detected the CVB3 mRNA replication and CVB3 capsid protein VP1 expression following the change of autophagy. Here, it was showed that ZSTK474 and Rapamycin promoted CVB3‑induced autophagy, as well as decreasing CVB3 mRNA replication and CVB3 capsid protein VP1 expression at 6 and 9 h p.i. ZSTK474 also alleviated CVB3‑induced autophagy, and decreased CVB3 mRNA replication and VP1 expression at 12 and 24 h p.i. However, Rapamycin continued to promote CVB3‑induced autophagy and increase CVB3 mRNA replication at 12 and 24 h p.i, as well as increase VP1 expression at 12 h, but not at 24 h, p.i. In the present study, we found Rapamycin and ZSTK474 have differential effects at different p.i. time‑points regarding CVB3 replication and CVB3‑induced autophagy. This indicates that the association between CVB3‑induced autophagy and viral replication depends on the infection time. During the early course of infection, autophagy may help host cells clear the virus, thereby providing protection, whereas when the infection time increases, autophagy may be exploited for viral replication.

Background/Aims: Hereditary spherocytosis (HS) is a common pediatric hemolytic anemia caused by congenital red blood cell defects. HS due to ankyrin 1 (ANK1) mutations is the most common type. We explored an ANK1 mutation from an HS patient and reviewed the literature. Methods: We detected the mutation in a Chinese family in which 2 members were diagnosed with HS by next-generation sequencing. The proband was diagnosed with HS in the newborn period, based on clinical manifestations, laboratory data, and family history. The mutation spectrum of the ANK1 gene was summarized based on 85 patients diagnosed with HS carrying ANK1 mutations, and the ANK1 mutation spectrum was summarized and analyzed. Results: We identified a novel mutation affecting ANK1 gene splicing (a splicing mutation) in both the patient and her mother, which is a substitution of T>G 2 nt after exon 25 in intron 26. The study expands our knowledge of the ANK1 gene mutation spectrum, providing a molecular basis for HS. Conclusion: A novel ANK1 mutation (NM_000037.3, c.2960+2T>G, intron 26) that is potentially associated with HS was identified. To date, 80 ANK1 mutations have been reported to be associated with HS in humans.

Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects children and can result in coronary artery lesions (CALs). Thrombomodulin (TM) is a critical cofactor in the protein C anticoagulant system. The TM C1418T (rs1042579) polymorphism is associated with a high risk of cardiac-cerebral vascular diseases. But the association of the TM C1418T polymorphism with susceptibility to KD, CAL formation, and intravenous immunoglobulin (IVIG) resistance is still unclear. In our study, we examined the TM C1418T polymorphism in 122 children with KD and 126 healthy children and revealed the correlation between the TM C1418T polymorphism and KD, CAL formation, and IVIG resistance.

Coxsackievirus B3 (CVB3) is an important human pathogen linked to cardiac arrhythmias and acute heart failure. CVB3 infection has been reported to induce the formation of autophagosomes that support the viral replication in host cells. Interestingly, our study shows that the accumulation of autophagosomes during CVB3 infection is caused by a blockage of autophagosome–lysosome fusion rather than the induction of autophagosome biogenesis. Moreover, CVB3 decreases the transcription and translation of syntaxin 17 (STX17), a SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) protein involved in autophagosome–lysosome fusion. Overexpression of STX17 restored the autophagic flux, alleviated the virus-induced lysosomal dysfunction, and decreased the apoptosis induced by CVB3 infection in HeLa cells. Taken together, our results suggest that CVB3 infection impairs the autophagic flux by blocking autophagosome–lysosome fusion. These findings thus point to potential new therapeutic strategies targeting STX17 or autophagosome–lysosome fusion for treating CVB3-associated diseases.

Kawasaki disease (KD) is an autoimmune disorder that can induce coronary artery aneurysms, particularly in the case of delayed diagnosis and/or treatment. Early diagnosis is important for treatment and reduces the risk of heart injury. The aim of the present study was to identify differentially expressed genes by comparing the levels of gene expression in human umbilical vein endothelial cells following treatment with plasma from healthy individuals and patients with acute or convalescent KD. Following comparison of the control and acute KD groups, 385 up-regulated and 537 down-regulated genes were identified in the acute KD group. In the convalescent group, 505 and 879 genes were up-regulated and down-regulated, respectively, relative to the control group. Genes involved in the immune system and cell growth factors were up-regulated, while genes functioning in methylation were down-regulated, following treatment with KD plasma. In addition, five potential candidate molecular markers of KD, C-X-C motif chemokine ligand 2 (CXCL2), interleukin (IL) 8, tripartite motif containing 58 (TRIM58), immunoglobulin superfamily member 3 (IGSF3) and runt related transcription factor 1 (RUNX1) were identified by microarray analysis and verified using quantitative polymerase chain reaction. A significant positive correlation was identified between the neutrophil polys and expression levels of four of these candidate genes, including CXCL2, IL8, TRIM58, and IGSF3 (all P

Exosome, a nano-grade biological membrane structure, is secreted by multiple cells, widely distributing in saliva, plasma, milk and other body fluid. It can directly and indirectly take part in the biological information transcription between the receptor cells and their micro-environment. Recent studies have demonstrated that exosomes play pivotal roles in the occurrence and development of viral infectious diseases, tumors and other cell apoptosis related diseases via regulating the apoptosis in various ways.外源性外泌体是一种纳米级的生物膜结构，由多种细胞分泌，广泛分布于唾液、血浆、乳汁等体液中，可直接或间接参与受体细胞及其微环境的生物信息转录。它可通过多种方式高效参与细胞凋亡的发生、发展，在病毒感染性疾病、肿瘤的发生和发展等生物进程中发挥着重要的作用。.