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简介：AbstractBackground:Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.Methods:Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student’s t test.Results:Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).Conclusion:These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.

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简介：AbstractBackground:Endolymphatic sac tumor (ELST) is one of neuroectodermal tumor which arising from endolymphatic sac and duct. It is actually quite rare, with less than 200 cases reported. Although ELST presents benign appearance in histopathology, it can present aggressive destructive behavior in clinical. The cornerstone of treatment for ELST is complete surgical excision. However, it is almost impossible to completely resect the advanced stage tumor. There is still controversy about other treatments, such as radiotherapy and gamma knife surgery.Case presentation:A 47-year-old man was admitted in The First Affiliated Hospital of Fujian Medical University with a 7-year history of progressive hearing loss and near 6-month repeated attacks of headache. Preoperative CT revealed a massive intracranial lesion and associated hydrocephalus. MR scanning demonstrated a 7.2 cm × 4.6 cm × 4.2 cm bulky mass located in left-sided posterior cranial fossa and temporo-occipital region which showed hyperintensity on T1-weighted images and mixed signal intensity on T2-weighted images. There was no neither clinical manifestation nor family history of Von Hippel-Lindau syndrome (VHL).Due to the mass that was large and invading the bone of skull base, it was difficult to extirpate surgically, so the ventriculoperitoneal shunt combined with local biopsy was performed. The postoperative pathology and immunohistochemical findings confirmed the lesion was an endolymphatic sac tumor. After operation, the patient regularly received radiotherapy.Conclusion:The widely accepted management of ELST is complete surgical resection. However, it is difficult for surgeons to achieve radical resection with late-stage ELST. Currently, there is much dispute about the role of radiotherapy for the management of ELST in academic circles. In this case where the mass cannot be surgical removed, radiotherapy has the curative effect for ELST in terms of disease control and quality of life.

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简介：AbstractIntroduction:There is a known association between primary mediastinal germ cell tumor (PMGCT) and hematologic malignancy that is not linked to treatment. They are exceptionally rare entities with a low morbidity and a poor prognosis.Case presentation:An 11-year-old boy presented with an anterior mediastinal mass diagnosed as a malignant germ cell tumor on the basis of an excisional biopsy. He was found to have acute myeloid leukemia (AML) two years after the chemotherapy for his germ cell tumor. The clinical course was very aggressive with a survival time of only 1 week after diagnosis of AML associated with PMGCT.Conclusion:AML associated with PMGCT needs to be diagnosed correctly. Relevant examinations should be carried out in patients with PMGCTs during and after chemotherapy, and long-term follow-up is still necessary to reduce the risk of morbidity and mortality.

简介：AbstractObjective:To investigate the effects of vitrification on the expression of the imprinted gene Snrpn in neonatal placental tissue.Methods:Neonatal placental tissue was collected from women with natural pregnancy (control group) and from women in assisted reproductive technology (ART) pregnancy group, following fresh and vitrified embryo transfer (fresh group and vitrified group, respectively). Snrpn mRNA expression and SNRPN protein levels in placental tissue from these three groups were assessed by real-time reverse transcription polymerase chain reaction and Western blot, respectively. DNA methylation in the Snrpn promoter region was analyzed by bisulfite-pyrosequencing.Results:The expression of Snrpn mRNA and SNRPN protein was found to be higher in placental tissue from the fresh and vitrified ART groups, compared to the control group. There was no significant difference in SNRPN gene or protein expression between the fresh and vitrified groups. DNA methylation at the Snrpn promoter region was not significantly different between these three groups.Conclusions:Human ART may alter the transcriptional expression and protein levels of the imprinted gene Snrpn. However, compared to other ART methods, vitrification may not aggravate or reduce this effect. Moreover, the altered expression of Snrpn is likely not directly related to DNA methylation of the Snrpn promoter region.

简介：AbstractBackground:Applying ultrasonic imaging system during surgery requires the poring of saline, performing the measurement, and acquiring data from its display—which requires time and is highly "performer dependent," i.e., the measure is of a subjective nature. A new ultrasonic device was recently developed that overcomes most of these drawbacks and was successfully applied during tumor-in-brain neurosurgeries. The purpose of this study was to compare the two types of US devices and demonstrate their properties.Methods:The study was performed in the following stages: (i) an ex vivo experiment, where slices of the muscle and brain of a young porcine were laid one on top the other. Thicknesses and border depths were measured and compared, using the two types of US instruments. (ii) During human clinical neurosurgeries, tumor depth was compared by measuring it with both devices. (iii) Following the success of stages (i) and (ii), using solely the new US device, the tumor thickness was monitored while its resection. Correlation, Pearson’s coefficient, average, mean, and standard deviation were applied for statistical tests.Results:A high correlation was obtained for the distances of tissue borders and for their respective thicknesses. Applying these ultrasonic devices during neurosurgeries, tumor depths were monitored with high similarity (87%), which was also obtained by Pearson’s correlation coefficient (0.44). The new US device, thanks to its small footprint, its remote measurement, and the capability of monitoring intraoperatively and in real-time, provides the approach to tumor’s border before its complete resection.Conclusions:The new US device provides better accuracy than an ultrasonic imaging system; its data is objective; it enables to control the residual tumor thickness during its resection, and it is especially useful in restricted areas. These features were found of great help during a tumor-in-brain surgery and especially in the final stages of tumor’s resection.

简介：AbstractThe emergence of mobile Tigecycline-resistant tet(X3) and tet(X4) is believed to be a global threat to public health. Here, we investigated the prevalence of tet(X3) and tet(X4) in our metagenomic data of migratory birds. While tet (X4) was not identified in our samples, tet(X3) was found in two gut microbiomes of bird fecal samples, with 100% amino acid identity of sites 150–387. These results suggest that tet(X3) has been spreading into the environment for a long period of time and that there is an urgent need to control its further transmission.

简介：AbstractMolecular imaging is of great significance for early diagnosis and timely treatment of cancer and disease, as well as basic medical and biological research. As personalized cancer treatment has become increasingly popular, the demand for more advanced imaging technologies has also significantly increased. Taking advantage of differences between the tumor microenvironment and normal tissue cells, tumor microenvironment-responsive or "turn-on" contrast agents have a higher signal-to-noise ratio and lower background interference compared with "turn-off" probes, which can remarkably improve the performance of tumor diagnostics. Thus, tumor microenvironment-responsive contrast agents can not only detect changes in the tumor microenvironment, but also have important significance for tumor diagnosis, prediction of invasion potential, evaluation of treatment effectiveness, planning of therapeutic regimens, and tumor prognosis. Herein, this review focuses on recent research progress of tumor microenvironment-responsive intelligent probes, and highlights future research directions of tumor microenvironment-responsive contrast agents for precision diagnostics.

简介：AbstractObjective:It has recently been shown that the melanoma antigen gene (MAGE) family is expressed in various tumor cell lines but silent in normal tissues, except germ cell lines. Mageb4, a member of the MAGE family, is highly expressed in the testis and homologous in humans and mice. Whole-exome sequencing studies have identified Mageb4 as a possible X-linked cause of inherited male infertility. However, the function of Mageb4 protein remains largely unknown.Methods:Using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 technology, we generated a Mageb4 knockout mouse model (Mageb4-/Y) to explore the role of this gene in spermatogenesis.Results:First, immunostaining of testicular cells showed that Mageb4 is localized in the cytoplasm of spermatogonia. Second, Mageb4-/Y male mice displayed significant increases in apoptosis. However, Mageb4-/Y male mice showed normal fertility, including normal sperm concentration, sperm motility, and testicular and epididymal histology.Conclusions:These findings suggest that, despite testis-exclusive expression, Mageb4 is dispensable for mouse spermatogenesis. Future research should focus on the role of this gene in apoptosis, aiming to provide clinical guidance regarding male infertility.

简介：AbstractBackground:The hypocaloric diets improve glycemic status in obese individuals, but the response to hypocaloric diets in fat mass and obesity-associated gene (FTO)-rs9939609 gene variant is unknown. This systematic review and meta-analysis aimed to assess the gene-diet interaction of FTO-rs9939609 gene variant and hypocaloric diets on glycemic control in overweight and obese adults.Methods:Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science, Embase, Scopus, and Google scholar were searched up to December 2018, for relevant clinical trials. Mean changes in fasting blood sugar (FBS), serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were extracted.Results:The pooled analysis of nine studies showed that there was no significant difference between AA/AT and TT genotypes in FBS (weighted mean difference [WMD] = 0.01, 95% confidence interval [CI]: -1.08, 1.10, P = 0.984) and serum insulin (WMD = 0.20, 95% CI: -0.85, 1.26; P = 0.707) after intervention hypocaloric diets. The overweight/obese participants in AA/AT group showed the greatest reduction in HOMA-IR compared with TT genotype following intervention, and this difference was not statistically significant (WMD = -0.38, 95% CI: -0.94, 0.16, P = 0.167).Conclusion:This meta-analysis suggests that there was no significant difference between AA/AT and TT genotypes of FTO-rs9939609 on FBS, serum insulin level, and insulin resistance in response to hypocaloric diets.

简介：AbstractBackground:Interleukin-18 (IL18) gene polymorphisms are related to many inflammatory and autoimmune diseases. However, a correlation analysis between IL18-607C/A and -137G/C gene polymorphisms and Takayasu arteritis (TA) is lacking.Methods:This study enrolled 200 patients with TA as the case group and 334 region-, age-, and sex-matched healthy subjects as the control group. We genotyped alleles and genotypes at positions -607 and -137 of the IL18 gene and analyzed the distribution frequencies. Mann-Whitney U test, t test, Chi-squared test and Hardy-Weinberg equilibrium were performed.Results:After adjusting for risk factors, the adjusted odds ratios and 95% confidence intervals at position -607C/A were 0.533, 0.391 to 0.880 (P = 0.010); 0.266, 0.586 to 1.002 (P = 0.051); and 0.122, 0.552 to 1.420 (P = 0.613) under the dominant, additive, and recessive models, respectively. For the -137G/C polymorphism, the adjusted odds ratios and 95% confidence intervals were 1.571, 1.068 to 2.311 (P = 0.022); 1.467, 1.086 to 1.980 (P = 0.012); and 1.815, 0.901 to 3.656 (P = 0.095) under the dominant, additive, and recessive models, respectively. Moreover, regardless of the model used, we found no statistical difference in distribution frequency between the active and quiescent states of TA for the -607C/A (P = 0.355, 0.631, and 0.705, respectively) and -137G/C polymorphisms (P = 0.205, 0.385, and 0.208, respectively).Conclusions:The IL18-607C/A gene polymorphism may decrease the risk of TA, and thus is a protective factor, whereas -137G/C may increase the risk of TA, and thus is a risk factor. However, neither polymorphism was related to activity (active vs. quiescent) of TA.

简介：AbstractColistin is an old antimicrobial that has been revitalized as last-resort treatment against multidrug-resistant (MDR) gram-negative bacterial infections. However, colistin has been widely used in agricultural production and veterinary medicine for decades, and the recent global dissemination of mobilized colistin resistance (mcr) genes from animals to humans seriously threats the clinical use of colistin. Most of the mcr-harboring isolates have been Enterobacteriaceae, such as Escherichia coli and Salmonella enterica which are common to animals and humans. An understanding of the origin, dissemination and transmission of mcr genes in bacteria common to animals and humans will facilitate the management of colistin use and relevant interventions to prevent further spread of resistance. This review aims to provide a comprehensive assessment of the global prevalence and transmission of mcr genes of animal and human commensal/pathogenic bacteria.

简介：AbstractObjective:The purpose of this study was to examine the role of rare variants in the one-carbon metabolic pathway in the etiology of the cerebral folate deficiency (CFD) syndrome. The CFD syndrome is a neurometabolic syndrome identified by low concentrations of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF) in spite of near-normal peripheral folate levels resulting in neurodevelopmental disorders.Methods:The localized folate metabolism impairments in CFD are thought to be either the result of mutations in genes responsible for folate transport or folate turnover through degradation. Genes that have been previously implicated in the etiology of CFD include folate receptor alpha-1 (FOLR1), dihydrofolate reductase, proton-coupled folate transporter, and capicua. We performed whole-exome sequencing (WES) analysis of a CFD patient that revealed 99 novel missense mutations, of which 21 were classified as damaging mutations through the Poly-Phen2 prediction algorithm. In vitro functional studies were conducted by transient transfection of wild-type and mutant MTHFS into HEK293T cells to determine the impact of the variants on enzyme activity.Results:Of the damaging variants identified in the WES studies, we focused on the gene coding for the enzyme 5,10-methenyl-tetrahydrofolate synthetase (MTHFS). This enzyme catalyzes the production of methenyl THF which is subsequently converted to 5-MTHF. The CFD patient described within was found to carry a homozygous mutation, c.101G>T (p.R34L, rs200058464) in MTHFS, while the parents of the proband are heterozygotes for the MTHFS gene, and the healthy sibling is not a carrier.Conclusion:The mutant allele displayed a 50% reduction in luciferase activity (P < 0.05), suggesting that homozygous loss of the MTHFS gene may play a significant role in the development of CFD.

简介：AbstractBackground:Immune- and inflammation-related genes (IIRGs) play an important role in the pathogenesis of tuberculosis (TB). However, the relationship between IIRG polymorphisms and TB risk remains unknown. In this study, the gene polymorphisms and their association with tuberculosis were determined in a Chinese population.Methods:We performed a case-control study involving 1016 patients with TB and 507 healthy controls of Han Chinese origin. Sixty-four single-nucleotide polymorphisms (SNPs) belonging to 18 IIRGs were genotyped by the PCR-MassArray assay, and the obtained data was analyzed with χ2-test, Bonferroni correction, and unconditional logistic regression analysis.Results:We observed significant differences in the allele frequency of LTA rs2229094*C (P = 0.015), MBL2 rs2099902*C (P = 0.001), MBL2 rs930507*G (P = 0.004), MBL2 rs10824793*G (P = 0.004), and IL12RB1 rs2305740*G (P = 0.040) between the TB and healthy groups. Increased TB risk was identified in the rs930507 G/G genotype (Padjusted = 0.027) under a codominant genetic model as well as in the rs2099902 (C/T + C/C) vs T/T genotype (Padjusted = 0.020), rs930507 (C/G + G/G) vs C/C genotype (Padjusted = 0.027), and rs10824793 (G/A + G/G) vs A/A genotype (Padjusted = 0.017) under a dominant genetic model after Bonferroni correction in the analysis of the overall TB group rather than the TB subgroups. Furthermore, the rs10824793_rs7916582*GT and rs10824793_rs7916582*GC haplotypes were significantly associated with increased TB risk (P = 0.001, odds ratio [OR] = 1.421, 95% confidence interval [CI]: 1.152-1.753; and P = 0.018, OR = 1.364, 95% CI: 1.055-1.765, respectively). Moreover, the rs10824793_rs7916582*AT/AT or rs10824793_rs7916582*GT/GT diplotype showed a protective (P = 0.003, OR = 0.530, 95% CI: 0.349-0.805) or harmful (P = 0.009, OR = 1.396, 95% CI: 1.087-1.793) effect against the development of TB.Conclusions:This study indicated that MBL2 polymorphisms, haplotypes, and diplotypes were associated with TB susceptibility in the Han Chinese population. Additionally, larger sample size studies are needed to further confirm these findings in the future.

简介：AbstractPurpose:Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear.Methods:In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression.Results:Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing.Conclusion:Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

简介：AbstractBackground:Invasive sphenoid sinus aspergillosis is a rare but life-threatening condition usually found in immunocompromised patients. When involving cavernous sinus and surrounding structures, patients are frequently misdiagnosed with a neoplasm or sellar abscess. Timely diagnosis and intervention are crucial to patients’ outcomes. The objective of this study is to review cases of invasive sphenoid sinus aspergillosis to describe disease manifestations, imaging features, treatment, and outcome.Case presentation:We describe four patients with invasive sphenoid sinus aspergillosis misdiagnosed as sellar tumors preoperatively. The mass was completely removed in three patients and partially removed in one patient microscopically. Pathological examinations confirmed Aspergillus in all cases. All four patients received anti-fungal agents postoperatively. There was no recurrence at the time of each patient’s follow-up date. One patient with complete resection was lost to follow-up while the other three patients’ neurologic function improved. Additionally, we performed a systematic review regarding invasive sphenoid sinus aspergillosis of existing English literature.Conclusion:With regard to clinical symptoms, headache, vision impairment, and ophthalmoplegia were observed in over half of the patients in the literature. A sellar mass with bone destruction on CT and involvement of cavernous sinus is highly suggestive of invasive fungal sphenoid sinusitis. Immediate surgical removal of the lesion is recommended for invasive sphenoid sinus aspergillosis to preserve nerve function and increase the likelihood of survival.

简介：AbstractLung cancer is one of the leading causes of all cancer-related deaths. Circulating tumor DNA (ctDNA) is released from apoptotic and necrotic tumor cells. Several sensitive techniques have been invented and adapted to quantify ctDNA genomic alterations. Applications of ctDNA in lung cancer include early diagnosis and detection, prognosis prediction, detecting mutations and structural alterations, minimal residual disease, tumor mutational burden, and tumor evolution tracking. Compared to surgical biopsy and radiographic imaging, the advantages of ctDNA are that it is a non-invasive procedure, allows real-time monitoring, and has relatively high sensitivity and specificity. Given the massive research on non-small cell lung cancer, attention should be paid to small cell lung cancer.

简介：AbstractBackground:Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.Methods:CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.Results:Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.Conclusion:Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.