Brown-Sequard Syndrome ; etiology ; Cervical Vertebrae ; Humans ; Intervertebral Disc Displacement ; complications ; surgery ; Male ; Middle Aged

Background: We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. Conclusion miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

To investigate the clinical efficacy, feasibility and safety of new "three tubes" method in the treatment of spontaneous esophageal rupture. A total of 22 patients with spontaneous esophageal rupture were retrospectively analyzed. Through the new "three tubes" method of treatment, patients achieved leak cured with reduced hospital stay, less medical expenses and early resumption of oral diet. The new "three tubes" method for spontaneous esophageal rupture has the advantages of easy handling, minimal invasion, few complication and exact curative effect.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

OBJECTIVE: To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD). METHODS: A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD. RESULTS: There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P<0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P<0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P<0.05). CONCLUSIONS The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.
Autism Spectrum Disorder ; Bacteria ; Child ; Feces ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S

OBJECTIVETo investigate the effectiveness of foscarnet sodium in the treatment of severe chronic hepatitis B.

METHODSTwo hundred and eight patients were enrolled in a multicenter, double-blind, controlled study. The patients received foscarnet sodium (foscarnet group) or saline (control group) injections for 4 weeks, and were then followed for 24 weeks.

RESULTSHBV DNA negative rate was 12.8% in the foscarnet group and 7.1% in the control group at the end of treatment; and it was 5.5% and 3.0% at the end of the follow-up period respectively (P > 0.05). The rate of HBV DNA decrease of more than 2 log copies/ml was 53.2% in the foscarnet group and 16.2% in the control group at the end of treatment, and 23.9% and 8.1% (P < 0.01) respectively at the end of the follow-up period. The rate of HBV DNA < 10(5) copies/ml was 64.2% and 30.3% at week 4 in the two groups respectively, and 40.4% and 22.2% (P < 0.01) at the end of the follow-up period. HBeAg negative rate was 17.3% and 5.8% at the end of the treatment, and 22% and 5.4% at the end of the follow-up period (P < 0.01). The rate of HBeAg seroconversion was 12.7% and 3.7% at week 4, and 16.7% and 1.5% at the end of the follow-up period. Response rate was 60.6% and 21.2% at the end of week 4 (P < 0.05).

CONCLUSIONFoscarnet sodium injection has a good effect on severe chronic hepatitis B patients and it is safe to use on them.

Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Foscarnet ; adverse effects ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Young Adult

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.
Animals ; Disease Models, Animal ; Leukemia, Biphenotypic, Acute ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Fusion ; genetics ; Retroviridae ; genetics ; Transfection

Objective To investigate the expression of signal transducer and activator of transcription 5 b (Stat5 b) and its phosphorylation (p-Stat5 b) in cervical lesions, its relationship with different degrees of cervical lesions, and its role in the pathogenesis and development of cervical lesions. Methods We obtained 80 specimens, including normal cervical tissues, low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cervical cancer tissues. To analyze the correlation between Stat5 b and the degree of cervical lesions, immunohistochemical staining was performed to detect Stat5 b and p-Stat5 b expression. Results Increased Stat5 b expression had a positive correlation with the development of cervical lesions. The percentages of Stat5 b expressed in normal tissues, LSIL, HSIL, and cervical cancer tissues were 15.0％, 0.0％, 50.0％, and 80.0％, respectively, with significant differences among the groups (P ＜ 0.05). Conversely, the expression of p-Stat5 b had a negative correlation with the development of cervical lesions.Expression of p-Stat5 b in normal tissues, LSIL, HSIL, and cervical cancer tissues was 80.0％, 45.0％, 5.0％, and 0.0％, respectively, with statistically significant differences among the groups (P ＜ 0.05). Conclusion The expression of Stat5 b is significantly different in different degrees of cervical lesions, suggesting that Stat5 b signaling molecules may be involved in the development of cervical lesions.

Objective To investigate the effects of camel milk on immune cells in lamina propria (LP) of intestinal mucosa in mice. Methods Six male C57BL/6 mice(6-8 weeks) were randomly divided into two groups as follows: camel milk treatment group and double distilled water (DDW) control group. Samples of cells in LP of intestinal mucosa were collected. Cell counts and percentages of immune cells in LP were analyzed by flow cytometry. Levels of IL-4,IL-10,IL-17 and IFN-γ in the supernatants of cell cul-ture were measured by ELISA. Results Compared with the DDW control group, the camel milk treatment group showed increased percentage and absolute number of CD4+T cells as well as IFN-γ-secreting CD4+T cells in LP of intestinal mucosa(P<0.05). Moreover,significantly enhanced expression of IFN-γ and sup-pressed secretion of IL-4 were found in the camel milk treatment group (P<0.05). Conclusion Camel milk can promote the proliferation of CD4+T cells and enhance the secretion of IFN-γ,indicating that camel milk regulates the proliferation and cytokine secretion of immune cells in LP of intestinal mucosa in healthy mice.

OBJECTIVE Tissue plasminogen activator (tPA) is the only approved pharmaco-logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans-formation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation. METHODS Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion, tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg-1).Mice were killed at 24 h post ischaemia, and their brains were evaluated for brain infarction, oedema, haemoglobin content, apoptosis, neuroinflammation, blood-brain barrier (BBB) permeability, the expression of tight junction proteins(TJPs)and the activity/expression of MMPs. RESULTS In the mice infused with tPA at 5 h post ischaemia, there were significant increases in mortality, brain infarction, brain oedema, brain haemoglobin level, neural apoptosis, Iba-1 staining (microglia activation) and myeloperoxidase staining (neutrophil infiltration). All these tPA-induced alterations were significantly prevented by NMN administration. Mechanistically, the delayed tPA treatment increased BBB permeability by down-regulating TJPs, including claudin-1, occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2. Similarly, NMN administration partly blocked these tPA-induced molecular changes. CONCLUSION Our results demonstrate that NMN ameliorates tPA-induced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.