Sepsis-associated encephalopathy(SAE)is a common complication with high mortality in patients with sepsis, but its pathogenesis is not clear, and there is no recognized diagnostic criteria and specific treatment.Intestinal tract plays an engine-like role in the occurrence and development of sepsis.The destruction of intestinal barrier and the disorder of intestinal microorganisms can affect the outcome of sepsis, in which gut microbiome affect the pathophysiology of intestine and brain through " the microbiome-gut-brain axis" (MGBA), and "gut microbiome-mitochondrial crosstalk" explains its role at the organelle level.The gut microbiome disorder exists in SAE animal model, while fecal bacteria transplantation can improve the symptoms and prognosis, suggesting that the exploration of gut microbiome may be of certain significance to understand the mechanism of SAE and explore its treatment.Here we review from three aspects: the gut microbiome, MGBA and the role of gut microbiome in SAE.

ObjectiveTo observe protective effects of agmatine (AGM) on inflammatory response and spleen immune function in mice with trauma.Methods Forty-eight adult male C57BL/6 mice were randomly divided into three groups (n= 16 each), including control group, model group (bilateral femoral fracture and removal of 35% of the total blood volume), and AGM group (trauma/hemorrhage & AGM 200 mg/kg). Eight mice in each group were sacrificed at 3 hours and 24 hours, respectively, after modeling, and blood samples and tissue homogenate of spleen and liver were collected. The contents of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β) in serum and liver tissue were determined with enzyme linked immunosorbent assay (ELISA). Serum aspartate transaminase (AST), alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) were determined with automatic biochemistry analyzer. Spleen proliferation response stimulated with concanavalin A (ConA) was evaluated with methyl thiazolyl tetrazolium colourimetry (MTT).γ-interferon (IFN-γ) and IL-2 releases were determined with ELISA.Results Compared with control group, 3 hours after trauma/hemorrhage, the levels of serum TNF-α, IL-6, and IL-1β in model group were significantly elevated [TNF-α (ng/L): 145.38±31.50 vs. 23.06±11.14, IL-6 (ng/L): 496.94±50.76 vs. 47.13±17.47, IL-1β (ng/L): 321.31±43.02 vs. 29.25±16.24,allP< 0.01]. It was found that AGM treatment could alleviate the increase in serum pro-inflammatory mediators induced by trauma/hemorrhage, such as TNF-α (ng/L:111.56±25.47 vs. 145.38±31.50), IL-6 (ng/L: 412.56±44.33 vs. 496.94±50.76), IL-1β (ng/L: 273.38±45.25 vs. 321.31±43.02,P< 0.05 orP< 0.01). Twenty-four hours after trauma/hemorrhage, serum pro-inflammatory mediators were recovered to the levels in control group. There was no significant difference in TNF-α and IL-6 levels at 3 hours after trauma/hemorrhage among groups. Compared with control group, the expressions of liver TNF-α and IL-6 in model group were increased at 24 hours following trauma [TNF-α (ng/mg): 32.93±4.90 vs. 26.58±2.33, IL-6 (ng/mg): 11.20±1.66 vs. 8.38±0.89,bothP< 0.01]. However, AGM inhibited the level of TNF-α (ng/mg:28.92±3.16 vs. 32.93±4.90) and IL-6 (ng/mg: 9.03±1.28 vs. 11.20±1.66) in the liver as induced by trauma/hemorrhage (P< 0.05 andP< 0.01). At 24 hours after modeling, model group and AGM group had distinctly higher serum AST, ALT, LDH levels than those of control group [AST (U/L): 405.9±31.2, 245.7±22.1 vs. 128.2±15.9; ALT (U/L): 92.1±6.3, 51.6±5.0 vs. 30.1±3.2; LDH (U/L): 606.7±36.3, 478.7±25.3 vs. 384.0±16.6, allP< 0.01]. Nevertheless,the increase in serum AST, ALT and LDH was alleviated in AGM group (allP< 0.01). Meantime, trauma/hemorrhage produced a noticeable depression of proliferation of splenic cells and IFN-γ and IL-2 release stimulated with ConA compared with control group [proliferation rate: (40.97±4.13)% vs. (89.99±7.76)%, IFN-γ(ng/L): 91.6±12.3 vs. 353.2±21.5,IL-2 (ng/L): 53.4±6.4 vs. 91.0±12.2,allP< 0.01]. In contrast, AGM notably restored the capacity of proliferation response of splenic cells [proliferation rate: (74.86±5.75)% vs. (40.97±4.13)%, P< 0.01],enhanced the release of IFN-γ and IL-2 stimulated with ConA [IFN-γ (ng/L): 327.8±23.6 vs. 91.6±12.3, IL-2 (ng/L): 74.8±10.4 vs. 53.4±6.4, bothP< 0.01].Conclusion AGM can dramatically alleviate spleen immunosuppression, excessive inflammation and organ damage induced by trauma/hemorrhage.

Objective:To investigate the efficiency and pharmacoeconomics of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for mobilization of peripheral blood stem cells (PBSCM) in patients with multiple myeloma (MM).Methods:The data of 91 patients with newly treated MM who were hospitalized in the First Hospital of Jilin University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2015 to October 2017 were retrospectively analyzed. According to the patient's wishes, a high-dose chemotherapy combined with subcutaneous injection of PEG-rhG-CSF or recombinant human granulocyte colony-stimulating factor (rhG-CSF) was used for stem cell mobilization in 42 and 49 patients, respectively. The number of mononuclear cells (MNC) and CD34 + cells collected after mobilization, the maximum absolute neutrophil count (mANC), the cost of mobilization, and the engraftment time of white blood cells and platelets after transplantation were compared between the two groups. Results:The median number of MNC collected after mobilization in the PEG-rhG-CSF group and rhG-CSF group were 5.86×10 8/kg [(1.08-24.54)×10 8/kg] and 6.61×10 8/kg [(0.83-33.80)×10 8/kg], and the difference was not statistically significant ( U = 883.00, P = 0.245); while the median number of CD34 + cells collected after mobilization in the PEG-rhG-CSF group was higher than that in the rhG-CSF group [5.56×10 6/kg (0.94-19.90)×10 6/kg and 4.82×10 6/kg (1.12-14.61)×10 6/kg], and the difference was statistically significant ( U = 732.00, P = 0.038). The median number of mANC during mobilization in the PEG-rhG-CSF group was lower than that in the rhG-CSF group [20.50×10 9/L (7.26-61.30)×10 9/L and 32.08×10 9/L (6.92-69.99)×10 9/L], and the difference was statistically significant ( U = 490.00, P = 0.001). After autologous stem cell transplantation (ASCT), the time-to-recovery of white blood cell count (WBC) to 1.0×10 9/L in the PEG-rhG-CSF group was shorter than that in the rhG-CSF group [(11.59±1.98) d vs. (12.93±2.83) d], and the difference was statistically significant ( t = -2.395, P = 0.019), and the time-to-recovery of platelet count (Plt) to 20.0×10 9/L in the PEG-rhG-CSF group was also shorter than that in the rhG-CSF group [(12.86±2.62) d vs. (14.80±5.47) d], but the difference was not statistically significant ( t = -1.749, P = 0.085). The total mobilization cost of the PEG-rhG-CSF group was not statistically different from that of the rhG-CSF group [(21 405.47±7 365.98) yuan vs. (22 976.83±10 264.34) yuan, t = -0.721, P = 0.474]. Conclusions:PEG-rhG-CSF combined with high-dose chemotherapy is an effective option for PBSCM in MM patients, and its mobilization cost is equivalent to rhG-CSF. Therefore, PEG-rhG-CSF may be a better choice for PBSCM in MM patients.

Hematopoietic stem cell transplantation(HSCT), as a technique to reconstruct normal hematopoietic and immune function, has become a treatment option for a variety of malignant and non-malignant diseases in children.With the development of medical technology, the long-term survival rate of children after HSCT is significantly improved.At the same time, there is more concern and awareness about the late effects of HSCT.As one of the endocrine complications with the highest incidence in children after HSCT, gonadal damage leads to sex hormone secretion disorder, adolescent dysplasia, and infertility in adulthood, which has a serious influence on children′s mental health and quality of life.Therefore, it is helpful to reduce the psychological and economic burden on children and their families by understanding its potential mechanism, evaluating risk factors, screening early warning and recovery markers of gonadal function as well as taking corresponding preventive and protective measures.

Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.
Anoikis ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Connective Tissue Growth Factor ; metabolism ; DNA Methylation ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasm Metastasis ; rho GTP-Binding Proteins ; metabolism ; rho-Associated Kinases ; metabolism

Objective To analyze the clinical characteristics and risk factors for post-traumatic seizures (PTS) in children,so as to provide a theoretical evidence for clinicians to prevent PTS.Methods From January 2010 to November 2016,the clinical data and auxiliary examination of 388 post-traumatic patients hospitalized at the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively.According to the presence of epileptic seizure,these patients were divided into PTS group and non post-traumatic seizures (nPTS)group.The risk factors associated PTS were investigated by univariate analysis.Results Among the 388 post-traumatic children,72 cases had seizures,which occurred almost predominantly less than 1 year.Fifty-six point nine percent (41/72 cases) were immediately PTS,and 31.9％ (23/72 cases) were early PTS,and 11.1％ (8/72 cases) were late PTS.Among the seizures types,generalized seizures accounted for 51.4％ (37/72 cases),and tonic-clonic seizures were in common;focal seizures accounted for 36.1％ (26/72 cases);focal combined generalized seizures accounted for 2.8％ (2/72 cases),and the remaining 9.7％ (7/72 cases) were ominous.Electroencephalogram showed the slow wave and spike wave most common.There were significant differences in factors statistically,included age,Glasgow Coma Scale (GCS) score,the severity of traumatic brain injury,cerebral contusion,subdural hematoma,therapy method between the patients with seizures group and the patients without seizures group (Z =4.717,x2 =13.079,17.852,5.664,17.457,5.496,all P ＜ 0.05).In single factor analysis and multi-factor regression analysis,age,GCS score,the severity of traumatic brain injury,subdural hematoma,therapy method were associated with the incidence of PTS (all P ＜ 0.05).Conclusions PTS is a severe complication of brain trauma in children.Small age,GCS ≤8 scores,severe brain injury,subdural hematoma,surgery are the risk factors of PTS.

Testicular adrenal rest tumor (TART) is frequently complicated by congenital adrenal hyperplasia, which is a benign tumor of the testes frequently found in adolescents and adults.Palpation and scrotal ultrasound are the main diagnostic methods for TART.Poorly managed TART often results in testicular dysfunction or even infertility due to tumor compression.This article reviews the pathogenesis, epidemiology, clinical features, diagnosis, differential diagnosis and treatment of TART, thus improving the understanding of the disease to achieve early diagnosis, early treatment, and improved prognosis.

Objective:To explore the clinical significance of serum nuclear factor κ B, interleukin(IL)-4, IL-10, IL-12, interferon(IFN)- γ expression in subclinical hypothyroidism with gestational diabetes mellitus.Methods:Thirty pregnant women with subclinical hypothyroidism combined with gestational diabetes mellitus in Tangshan Maternal and Child Health Hospital from January 2017 to October 2018 were retrospectively analyzed as group A. Thirty three pregnant women with subclinical hypothyroidism were selected as group B, 35 pregnant women with gestational diabetes mellitus as group C and 40 healthy pregnant women as control group.ELISA was used to detect NF-κB, IL-4, IL-10, IL-12 and IFN-γ, and the results were analyzed and compared.Results:The serum levels of NF-κB were (15.91±5.68), (13.22±5.23), (12.97±5.11), (9.74±3.85) μg/L, IL-12 were (28.91±6.84), (21.64±5.72), (22.23±5.91), (13.68±3.76) ng/L, and serum IFN-γ levels were (23.74±5.55), (18.26±4.63), (17.85±4.31), (12.69±3.85) ng/L in A, B, C and the control group respectively.There were statistically significant differences in the three indicators between groups ( F=5.118, 6.821, 7.133, all P<0.05), and group A was higher than group B, C and control, the differences were statistically significant (all P<0.05); the levels of serum IL-4 in group A, B, C and control group were (8.91±3.99), (10.84±4.47), (11.27±4.62), (13.68±5.46) ng/L, respectively.The levels of serum IL-10 were (10.91±3.86), (13.05±4.58), (12.83±4.69), (15.82±5.33) ng/L, respectively.The differences of serum IL-4 and IL-10 between groups were statistically significant ( F=5.075, 5.616, all P<0.05), and serum IL-4 and IL-10 in group A were lower than those in group B, group C and control group.The levels of serum IL-4 and IL-10 in group B and C were lower than those in control group (all P<0.05). Conclusion:The activation of NF-kB signaling pathway and its related cytokines may be the influencing factors for the development of subclinical hypothyroidism with gestational diabetes mellitus.

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with split hand/split foot malformation (SHFM). METHODS: The patients were screened for genome-wide copy number variations with single nucleotide polymorphism (SNP) microarray. Copy number variations were verified by real-time fluorescence quantitative PCR. RESULTS: There were 3 SHFM patients from three generations, which conformed to an autosomal dominant inheritance. SNP microarray assay revealed that all patients have carried a 0.34 Mb duplication in 10q24.31-q24.32 (102 993 649-103 333 271) encompassing the BTRC and DPCD genes. The result was verified by real-time fluorescence quantitative PCR, confirming that the duplication has co-segregated with the SHFM phenotype in the pedigree. CONCLUSION The 10q24.31-q24.32 duplication probably underlies the pathogenesis of SHFM in this pedigree. Tiny copy number variations can result in diseases featuring autosomal dominant inheritance.
Asian Continental Ancestry Group ; China ; Chromosome Duplication ; Chromosomes, Human, Pair 10 ; genetics ; DNA Copy Number Variations ; Foot Deformities, Congenital ; genetics ; Hand Deformities, Congenital ; genetics ; Humans ; Mutation ; Pedigree ; Polymorphism, Single Nucleotide

Antiporters/genetics* ; Carcinoma, Papillary/pathology* ; Humans ; Neoplasm Metastasis/genetics* ; Sulfate Transporters/genetics* ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*