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BackgroundThe APLAID syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the PLCG2 gene. We present a 7-year-old APLAID patient who has recurrent blistering skin lesions, skin infections in the perineum, a rectal perineal fistula, and inflammatory bowel disease.MethodsTo determine the genetic cause of our patient, WES and bioinformatics analysis were performed. Flow cytometry was used for phenotyping immune cell populations in peripheral blood. Cytokines released into plasma were analyzed using protein chip technology. The PBMCs of patient and a healthy child were subjected to single-cell RNA-sequencing analysis.ResultsThe patient carried a novel de novo missense mutation c.2534T>C in exon 24 of the PLCG2 gene that causes a leucine to serine amino acid substitution (p.Leu845Ser). Bioinformatics analysis revealed that this mutation had a negative impact on the structure of the PLCγ2 protein, which is highly conserved in many other species. Immunophenotyping by flow cytometry revealed that in addition to the typical decrease in circulating memory B cells, the levels of myeloid dendritic cells (mDCs) in the children’s peripheral blood were significantly lower, as were the CD4+ effector T cells induced by their activation. Single-cell sequencing revealed that the proportion of different types of cells in the peripheral blood of the APLAID patient changed.ConclusionsWe present the first case of APLAID with severely reduced myeloid dendritic cells carrying a novel PLCG2 mutation, and conducted a comprehensive analysis of immunological features in the ALPAID patient, which has not been mentioned in previous reports. This study expands the spectrum of APLAID-associated immunophenotype and genotype. The detailed immune analyses in this patient may provide a basis for the development of targeted therapies for this severe autoinflammatory disease.

IntroductionHere, we report the case of an infant suffering from Alagille syndrome (ALGS), manifesting with the atypical clinical manifestations of prenatal oligohydramnios and renal lesions. To the best of our knowledge, this is the first case of ALGS presenting as prenatal oligohydramnios and renal lesions caused by a de novo variant of the NOTCH2 gene.Case presentationA 3-month-old male infant was hospitalized for severe malnutrition. He presented with prenatal oligohydramnios from 28+4 weeks of gestation. After birth, he failed to thrive and suffered from impaired motor development, thermoregulation disorders, congenital bilateral renal hypodysplasia, which initially manifested as stage 5 before improving to stage 3 chronic renal impairment, slightly elevated levels of transaminases, cholestasis, and dysmorphic facial features. We used a diagnostic screening panel of 4,047 pathogenic genes and whole exome sequencing (WES) to analyze the proband and his parents (who had normal kidneys). We found that the proband carried a de novo heterozygous splicing variant (c.5930-2A > G) in intron 33 of the NOTCH2 gene. Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping.ConclusionsOur case expands the spectrum of pathogenic variants of the NOTCH2 gene that are known to be associated with ALGS and characterized by prenatal oligohydramnios and renal lesions. It also reminds us of the necessity to monitor the liver and kidney function of the infant if a mother has oligohydramnios during pregnancy and we recommend ALGS as an additional differential diagnosis in prenatal renal abnormalities.

Purpose: To develop an oral vaccine against CVA16 (Coxsackievirus A16) by constructing a recombinant Lactococcus lactis that expresses VP1 from CVA16.Method: An oral CVA16 vaccine was prepared by expressing CVA16 VP1 protein with Lactococcus lactis. CVA16 VP1 gene was incorporated into a Lactobacillus expression vector, namely, pNZ8148, and then expressed in NZ9000, a food-grade lactic acid bacterium which serves as a carrier for oral vaccines.Results: There was statistically significant difference in CVA16-specific IgG antibody level between NZ9000-pNZ8148-CVA16-VP1 group (0.49 ± 0.05) and control group (0.05 ± 0.00) when the antiserum was diluted 1:10 (t = 19.84; p < 0.05). Furthermore, the level of CVA16-specific IgA antibody in NZ9000- pNZ8148-CVA16-VP1 group (0.17 ± 0.02) was significantly higher than in control group (0.05 ± 0.00) following antiserum dilution of 1:10 (t =12.08; p < 0.05).Conclusion: A CVA16 oral vaccine made from Lactobacillus elicits protective antibodies against CVA16. Thus, it is a potential as oral vaccine against CVA16 but further studies in vivo are required to ascertain its safety and effectiveness. Keywords: Coxsackievirus A16, Hand, foot and mouth disease, Lactococcus lactis, Oral vaccine, Enterovirus 71

Axin1 is a fundamental scaffolding protein of the destruction complex in the canonical Wnt signaling pathway, which plays a critical role in various biological processes. However, how Axin1 is regulated in the activation of the canonical Wnt signaling pathway remains elusive. Here, we report that Axin1 is constitutively acetylated in resting cells. Upon stimulation with Wnt, SIRT4 translocates from mitochondria to the cytoplasm and catalyzes Axin1 deacetylation, thus turning off the destruction complex. In this process, Lys147, a residue in the RGS domain of Axin1, plays a key role. We proved that the Axin1-K147R mutant impairs the assembly of β-TrCP to the destruction complex, which leads to β-catenin accumulation even without Wnt stimulation. In summary, our work proposes a new model for better understanding the initial stage of the canonical Wnt signaling pathway in which SIRT4 translocates from mitochondria into the cytoplasm to deacetylate Axin1-K147 after Wnt stimulation, which results in reduced assembly of β-TrCP to the destruction complex.

Background Renal cell carcinoma (RCC) is the most common renal malignant tumour. We evaluated the potential value and dose reduction of virtual non-contrast (VNC) images and virtual monoenergetic images (VMIs) from dual-layer spectral CT (DL-CT) in the diagnosis of RCC. Results Sixty-two patients with pathologically confirmed RCC who underwent contrast-enhanced DL-CT were retrospectively analysed. For the comparison between true non-contrast (TNC) and VNC images of the excretory phase, the attenuation, image noise, signal-to-noise ratio (SNR) and subjective image quality of tumours and different abdominal organs and tissues were evaluated. To compare corticomedullary phase images and low keV VMIs (40 to 100 keV) from the nephrographic phase, the attenuation, image noise, SNR and subjective lesion visibility of the tumours and renal arteries were evaluated. For the tumours, significant differences were not observed in attenuation, noise or SNR between TNC and VNC images (p > 0.05). For the abdominal organs and tissues, except for fat, the difference in attenuation was 100% within 15 HU and 96.78% within 10 HU. The subjective image quality of TNC and VNC images was equivalent (p > 0.05). The attenuation of lesions in 40 keV VMIs and renal arteries in 60 keV VMIs were similar to those in the corticomedullary images (p > 0.05). The subjective lesion visibility in low keV VMIs is slightly lower than that in the corticomedullary images (p Conclusion VNC images and VMIs acquired from DL-CT can maintain good image quality and decrease the radiation dose for diagnosis of RCC.

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a member of the CC chemokine family. CCL2 plays a crucial role in a wide range of biological processes. CCL2 mainly binds to its receptor CCR2 and recruits monocytes, macrophages and T lymphocytes. Many studies have shown that the CCL2-CCR2 axis promotes tumor cells growth and survival, angiogenesis, tumor invasion and metastasis. This review summarizes the role of CCL2-CCR2 axis in the development, progression and metastasis of prostate cancer, breast cancer and liver cancer, as well as the progress, prospects and challenges of clinical trials in targeting CCL2-CCR2 axis in tumor therapy.

A new type of discretized Lyapunov functional is introduced for stability and hybrid L2 × l2-gain analysis of linear impulsive delay systems. This functional consists of three parts. The first part is the conventional discretized functional for delay-independent stability analysis. The second part is the looped-functionals-like functional for exploiting the internal structure inside impulse intervals, in which the decision matrix functions are approximated by piecewise linear matrix functions. The third part is a discretized adjustive factor, which makes the proposed Lyapunov functional continuous along the system trajectories. Thanks to this continuity, the resultant criteria for exponential stability and finite hybrid L2 ×l2-gain are expressed in terms of a combination of the continuous and discrete parts of the system. It is shown through numerical examples that the accuracy of the stability test increases with the increase of the partition number on impulse intervals, and the convergence rate is faster than that of the previous discretized functionals-based approach.

Purpose To investigate the value of the iodine concentration (IC) measured by dual-layer detector spectral CT (DLDSCT) in evaluating the factors related to the treatment scheme and survival prognosis of patients with glioma. Methods From 2018 to 2019, we prospectively collected the data of 99 patients with glioma. The degree of CT enhancement and the IC of low grade gliomas (LGGs, II), high grade gliomas (HGGs, III and IV), grade II and III gliomas, were compared. The predictive performance of the degree of CT enhancement and IC was examined via receiver operating characteristic (ROC) analysis. The correlations between IC and Ki-67 labeling index, isocitrate dehydrogenase (IDH) mutation, chromosome 1p/19q deletion status of the tumor were examined. Results Both IC and the degree of CT enhancement of patients with HGG were significantly higher than those of patients with LGG (p Conclusions The DLDSCT technology can be used as a supplementary method to provide more information for preoperative grading of the gliomas and the prognosis assessment of the patients.

Sweden faces increasing pressures on health funding. Total expenditure on health care currently accounts for about 10.92% of GDP, which suggests an increase of about twofold over the last five decades. This paper examines the short-run and long-run relationship between income and health care expenditure in Sweden during the period 1980–2017. The study focused on the differences between short- and long-term elasticities. Consistent with the conventional findings, the income elasticity for health care is found to be greater than one, suggesting that health care is a luxury good in Sweden. Additionally, the age structure variable is found to have a significant positive impact on health care expenditure. Finally, the importance of another non-income variable, relative price, is also confirmed, an increase in relative price is associated with lower quantity of health care expenditure.

The aim of this study was to test the impact of variants rs900400 (located near LEKR1 and CCNL1) and rs9883204 (located in ADCY5) on birth weight in a Chinese population. We conducted a case–control study including 156 low-birth- weight infants as the case group and 100 normal-birth-weight infants as the control group. The rs900400 and rs9883204 variants were analyzed by gene sequencing in all the participants. Our results revealed a significant difference in the genotype distribution (χ2 = 10.449, p = 0.005) and allele distribution (χ2 = 9.277, p = 0.002) of rs900400 between the case group and the control group. The C allele of rs900400 was associated with lower birth weight (OR 1.771 [95 % CI 1.237–2.535]) in the Chinese population. However, the rs9883204 polymorphism was not informative in the Chinese population. Our study shows that the “birth weight-lowering” variant rs900400 located near LEKR1 and CCNL1, which is strongly associated with birth weight in European cohorts, appears to have a similar association in Chinese cohorts. However, the rs9883204 variant located in ADCY5 does not appear to be correlated with low birth weight in the same population. Moreover, we found that the variant rs900400 may also be associated with premature birth, thereby supporting the need for further research in this area.

International audience; In the first part of this review, some behavioural and environmental risk factors playing important roles in the development of Kazakh's oesophageal squamous cell carcinoma (OSCC) were presented. Although all individuals have been exposed to the same environment and share the same behaviour, some of them will not develop OSCC. Thus, gene susceptibility and/or gene polymorphism are unavoidably involved. The molecular events underlying the initiation and progression of OSCC remain, however, poorly understood. In the second part of our review of OSCC in northwestern China, especially in the high-risk Kazakh population, some recent progress in the study of the molecular biology underlying oesophageal carcinogenesis, including chromosome deletions and loss of heterozygocity, polymorphisms of genes involved in xenobiotic metabolizing and DNA repair, and genetic alterations of transcriptional factors and apoptosis genes are presented. Results obtained in this high-risk population are compared with those obtained in other areas that are also known to be at high risk for OSCC, and whenever possible, with those studies performed in European, American or Australian low-risk areas. Recent advances in the investigation of the proteomics and microRNA biomarkers potentially useful for an earlier diagnosis and/or prognosis of OSCC are also discussed.

An improve method of the block wise non-local means (BNL - means) is proposed for removing noise in the digital image. This method consists of the spectral decomposition of the Gaussian weighted matrix, the pseudo filter constructions, computations of the pseudo weighted coefficients and image denoising using the weighted sum of Gaussian. Experimental results show that this method is simpler, more efficient than the traditional NL-means algorithm and the denoising results are promising for the natural and textural image over the additive Gaussian white noise.

Objective To evaluate the protection of Danshen (Radix Salviae Miltiorrhizae) (SM) injection in myocardial infarction (MI) induced renal damage. Methods Forty male C57 mice were divided into control group, MI group and SM group. In MI group, the left coronary artery was occluded for 8 weeks; the same procedure was used for the SM group, with the additional step of SM (0.2 mL) administered intraperitoneally for 56 days. Before surgery and 8 weeks later, transthoracic echocardiography was performed and urine protein and albumin was measured. At the end of the time, all mice were killed and kidneys removed for reactive oxygen species (ROS) and fibrosis analysis, plasma was collected for blood urea nitrogen and serum creatinine determination. Results MI slightly decreased renal function and increased production of ROS, accompanied with renal fibrosis. Administration of SM reduced production of ROS and increased renal function, it also reduced renal fibrosis. Conclusion MI plays a causal role in renal injury and SM exerts renal-protective effects, probably by its antioxidant activities.