Agouti Signaling Protein ; Animals ; Central Nervous System ; abnormalities ; metabolism ; pathology ; Energy Metabolism ; Hair Color ; genetics ; physiology ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Membrane Proteins ; genetics ; metabolism ; physiology ; Mutation ; Obesity ; genetics ; metabolism

Autosomal recessive cutis laxa is a common type of hereditary cutis laxa. Its pathogenesis is not completely clear, but involved genes and their corresponding functions and signaling pathways have gradually become the research focus. According to the latest research, the related genes and their responding signaling pathways not only provide a solid foundation for the pathogenesis of cutis laxa, but also indicate a direction for instructing healthy pregnancy and scientific nurture. This paper aims to review the recent advances in pathogenic genes and potential signaling pathways in autosomal recessive cutis laxa.

【Objective】 To identify and analyze a case of ABO discrepancy between forward and reverse blood grouping, and to provide reference for the identification of ambiguous blood group in clinical. 【Methods】 ABO and Rh blood group typing, absorption and elution test, and gene sequencing were performed to confirm the ambiguous blood group. 【Results】 The sample was identified by absorption and elution test and molecular biological method to be Ael subtype, and was named ABO^*AEL.05/ABO^*O.01.01 by ISBT. After family investigation, the proband and her second son share the same characteristic mutation site, and was named ABO^*AEL.05/ABO^*B.01.01 by ISBT. 【Conclusion】 Multiple blood group serological tests and molecular biology tests help to identify ABO subtypes, thus assuring the safety, scientificity and rationality of clinical blood transfusion.

Objective To investigate the effect of microRNA (miR)-138 regulation of Wnt signaling pathway on the biological behavior of human glioma cells in vitro. Methods Glioma cell lines U-87MG and U251 were selected and randomly divided into blank group, miR-NC group, miR-138 mimics group and miR-138 inhibitor group. Real-time PCR was used to detect the miR-138 expression in each group; MTT, flow cytometry, Transwell assay and scratch assay were used to detect proliferation, apoptosis, invasion and migration ability of each group respectively, and Western blotting was used to detect Wnt pathway-related protein expression in each group. Results The miR-138 expression level was higher in the miR-138 mimics group compared with the remaining 3 groups, and that in the miR-138 inhibitor group was lower than that in the blank group and the miR-NC group (P<0. 05) ; Compared with the blank group, the cell proliferation rate was lower in the miR-138 mimics group and higher in the miR-138 inhibitor group, and was time-dependent (P<0. 05) ; The apoptosis rate in the miR-138 mimics group was higher than that in the blank group, miR-NC group, and miR-138 inhibitor group, while the apoptosis rate in the miR-138 inhibitor group was lower than that in the rest other groups (P<0. 05) ; The number of cell-invading cells in the miR-138 mimics group was lower than that in the blank group, miR-NC group, and miR-138 inhibitor group, while all miR-138 inhibitor group were higher than the remaining three groups (P<0. 05) ; The cell migration rate of miR-138 mimics group was lower than that of blank group, miR-NC group and miR-138 inhibitor group, while all miR-138 inhibitor group were higher than the remaining three groups (P<0. 05) ; Wnt3a, Wntl, glycogen synthase kinase 3(3(GSK-3(3) and (3-catenin protein expression in the miR-138 mimics group was lower than that in the blank group, miR-NC group, and miR-138 inhibitor group; While miR-138 inhibitor groups were higher than the remaining three groups(P<0. 05). Conclusion MiR-138 overexpression effectively inhibite the proliferation, invasion and migration of glioma cells and promote their apoptosis, probably achieved by pathway inhibition of the Wnt signaling pathway.

Objective : To research the feasibility and preliminary clinical effect of an implant-supported fixed bridge based on interactions with the posterior interocclusal space deficiency. Methods: Four patients with multiple implant-supported fixed-bridge restorations for interocclusal space deficiency in posterior teeth were included in this study. The 8 total implant sites had an average interocclusal space size of 3.3 mm. Two abutments with an undercut area were performed, the fixed bridge was placed by rotating it without a common path of insertion, and the abutment screw was then tightened. In the production process, the interaction retention concept and methods were fully communicated to the technician. The abutments and bridges on the implants were placed, and the clinical effect was observed. Results: The prosthesis was fixed well and presented appropriate functioning. At the 3-month and 18-month follow-up examination, the prosthesis and abutments were not loose, and the abutments did not release or break. No swelling or tenderness was observed in the margin of the implants. Conclusion The interaction retention is a good method of resolving the problem of interocclusal space deficiencies in the posterior teeth.

Objective: To evaluate the role of intestinal flora disturbance in perioperative neurocognitive disorders in aged mice. Methods: Sixty SPF healthy male C57BL/6J mice, aged 18 months, were divided into 4 groups (n=15 each) by a random number table method: control group (group C), operation group (group O), operation plus lactobacillus rhamnosus group (group OL) and operation plus fecal microbiota transplantation group (group OF). Exploratory laparotomy was performed in O, OL and OF groups.In group PL, lactobacillus rhamnosus 200 μl (1×10⁹ CFU/ml, 200 μl/day) was given by gavage once a day for 10 days starting from the end of surgery, and mice received about 0.2×10⁹ CFU probiotics per day.In group OF, broad-spectrum antibiotic mixture (ampicillin and sulbactam 1.5 g/L, vancomycin 500 mg/L, ciprofloxacin 200 mg/L, imipenem cilastatin 250 mg/L and metronidazole 1 g/L) was added to the drinking water at 7 weeks prior to operation and replaced with sterile tap water at 72 h before operation, and fecal filtrates 200 μl was given by gavage once a day for 10 days starting the end of operation.Five mice were sacrificed at day 10 after operation in each group, and Evans blue extravasation test was used to measure the vascular permeability of jejunum and ileum.Five mice were sacrificed at day 10 after operation in each group, and the small intestinal and hippocampal tissues and orbital venous blood samples were obtained for determination of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), IL-4 and IL-10 levels by enzyme-linked immunosorbent assay.Five mice were selected at day 10 after operation in each group, and the Morris water maze test was used to assess the cognitive function. Results: Compared with group C, the vascular permeability of jejunum and ileum was significantly increased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus were increased, the levels of IL-4 and IL-10 were decreased, the swimming distance and escape latency were prolonged, and the time spent in the target quadrant was shortened in group O (P<0.05 or 0.01), and no significant change was found in the parameters mentioned above in OL and OF groups (P>0.05). Compared with group O, the vascular permeability of jejunum and ileum was significantly decreased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus were decreased, the levels of IL-4 and IL-10 were increased, the swimming distance and escape latency were shortened, and the time spent in the target quadrant was prolonged in OL and OF groups (P<0.05). Conclusion Intestinal flora disturbance can mediate inflammatory responses in the hippocampus and cause perioperative neurocognitive disorders in aged mice.

Objective: To establish a nanometer magnetic particle chemiluminescence methodfor the detection of specific IgE antibodies to Tyrophagus putrefaciens allergen. Methods: According to the routine operation steps of chemiluminescence, chemiluminescence reaction system and suitable immune reaction conditions for detection of specific IgE of Tyrophagus putrescentiae allergen are established. Considering the performance of the chemiluminescence method established in this paper, the American Somerfly Phadia method wasused as the gold standard to evaluate the test performance of the established chemiluminescence method. Results: In thechemiluminescence reaction system, Luminol concentration in luminescent substrate A solution is 0.4 mg/ml, Urea hydrogen peroxidein luminescent substrate B solutionis 0.2 mg/ml.The sensitivity of this luminescent reaction system to horseradish peroxidase (HRP) is very high, the minimum detectable HRP is 0.01 ng/ml.In the immune response, the room temperature light-shielding reaction was detected for 5 min after the addition of substrates A and B, and the detection values were effective within 5-30 min. 37 ℃ is optimum luminescence reaction temperature. Choose the range of 0.35-100 IU/ml as the standard curve. According to the results of 120 clinical trials, using Phadia (immunofluorescence method) as the gold standard, the chemiluminescence method established in this study has significant significance for the detection of Tyrophagus putrescentiae allergen. Conclusion A nanometer magnetic particle chemiluminescence method was successfully established for the detection of specific IgE antibodies to Tyrophagus putrescentiae allergen.

Objective: To observe the influence of transcranial direct current stimulation (tDCS) on rapid eye movement sleep disorders among Parkinson′s disease (PD) patients. Methods: Fifty-four PD patients were randomly divided into a treatment group (n=28) and a control group (n=26). Both groups were given routine drug treatment and nursing, while the treatment group was additionally provided with tDCS therapy. Both groups were evaluated using polysomnography (PSG), the Hamilton depression scale (HAMD), the pediatric daytime sleepiness scale (PDSS), the Epworth sleeping scale (ESS) and PD quality of life questionnaire-39 (PDQ-39) before and after four months of treatment. Results: There were no significant differences between the two groups before the treatment. After the treatment, significant improvement was observed in the total sleep time (TST), sleep latency (SL), sleep efficiency (SE), rapid eye movement sleep (REMS), arousal index (AI), and in the HAMD, ESS, PDSS and PDQ-39 scores among the treatment group. In the control group only the average TST and HAMD score improved significantly. After the treatment, all of the treatment group′s average results were significantly better than the control group′s averages. Conclusion tDCS can significantly improve the sleep quality of patients with PD and relieve any depression, bettering their life quality.

Objective: To analyze the causes and management plan of pediatric spontaneous tonsillar haemorrhage(STH). Methods: According to the criteria of STH difined by Griffies, patients with STH from December 2013 to January 2016 were included in this retrospective study. Results: A total of 11 patients were reviewed. The etiological diagnosis included 3 pediatric Epstein-Barr virus associated infectious mononucleosis(EBV-IM), 3 suspected pediatric EBV-IM to 3 acute suppurative tonsillitis, 1 acute viral tonsillitis and 1 hemophilia A. The management strategies included antiviral, antibacteria, transfusion, surgical examination followed with bipolar coagulation hemostasis under general anesthesia. No patient treated with tosillectomy. Conclusions STH is now a rare condition, the causes of which in child are more or less different from adult.This emergency can be treated in time if a detailed management plan for pediatric STH is formulated.

There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.