L1 cell adhesion molecular is a type Ⅰ membrane glycoprotein of immunoglobulin superfamily. L1 is expressed mainly in nervous system and plays important roles in nervous system development, learning and memory. L1 cytoplasmic domain (L1CD) is important for L1 function by mediating signaling. To investigate the molecular mechanisms of signaling mediated by L1CD, yeast two-hybrid assay was carried out to screen the human brain cDNA library using L1CD as the bait. After sequence analysis and BLAST, several candidates were identified. One candidate is PAX6 transcription factor. L1CD and PAX6 cDNA were cloned in expression vectors and cotransfected into COS-7 cells. The interaction between L1CD and PAX6 was verified by co-immunoprecipitation assay. These preliminary results suggest that L1CD may be involved in transcription regulation.

Objective To explore the inhibition effect on angiogenesis and plaque growth of carotid atherosclerosis by transfection of endostatin gene using microbubbles combined with ultrasound exposure.Methods Twenty rabbit models of carotid atherosclerosis were randomly divided into 3 groups:group A,microbubble+ ultrasound; group B, control plasmid + microbubble + ultrsound; group C, ES plasmid +microbubble+ ultrasound. Two weeks after surgery, ultrasound/microbubble mediated gene transfer was performed,and it was performed once again three weeks after the first transfection. Ultrasonography and digital subtraction angiography(DSA) were performed at the time of 14 weeks. The carotid arteries were taken to detect the neointima and angiogenesis, and the expression of endostatin was detected using pathological means. Results The imagings of ultrasound showed that the intima in group A and B were thick significantly with larger plaques, and the lumen became stenosis with the peak systolic velocity increasing,however,in group C,the parameters mentioned above were significantly less than those of group A and B ( P＜0.05). Pathological results displayed that intima-media thickness (IMT), intima thickness (IT), intima thickness/media thickness (IT/MT), intima area (IA), intima area/media area (IA/MA) and neointimal stenosis rates were greater in group A and B, however, they were less in group C ( P＜0.05).The number of neovascularization and vascular endothelial growth factor(VEGF) expression in group A and B were more than those of group C. There was more endostatin positive expression in carotid arteries and anterior tibial muscles of group C, while there was nearly no expression in group A and B. Conclusions Under the conditioned ultrasonic irradiation, ultrasound/microbubble mediated endostatin gene transfection can inhibit the development of carotid atherosclerosis in rabbits, which might provide a safe and effective strategy for gene therapy of atherosclerotic disease in future.

ObjectiveTo investigate the effect of neuregulin1β (NRG1β) on the learning memory abilities and the neuronal apoptosis and the expressions of nuclear factor kappa B (NFκB) in experimental Alzheimer's disease model in rats induced with beta-amyloid protein1-40 (Aβ1-40) injection.To explore the mechanisms of NRG in improving the capabilities of learning and memory.MethodsThirty adult healthy male wistar rats were randomly divided into control group (n =10),model group (n =10) and treated group (n =10).Alzheimer's disease models were established by stereotactically injecting Aβ1-40 into the left lateral ventricle,and treated by injecting NRG1β(0.3 μg · kg-1 ) into the right lateral ventricle.The learning and memory abilities of rats were evaluated with Y-electric maze before the experiment and 7 days after making Alzheimer's disease models and 14 days after treatment.HE staining was used to observe the structure of hippocampal neurons.The neuronal apoptosis of hippocampus was investigated by TUNEL assay.The expressions of NFκB in hippocampal neurons were determined with immunohistochemistry technique.ResultsCompared with control group (57.50 ± 1.58,7.20 ±1.03 ),the model group rats ( 59.50 ± 2.79,7.50 ± 1.08 ) showed low cognitive ability ( t =20.36,5.28,P ＜0.05 ),the hippocampal pyramidal cells of rats in the model group were sparse and disturbed pyramidal cells,noticeable neuron loss.The number of neuronal apoptosis and the expressions of NFκB increased significantly than those in control group (P＜0.05).Compared with model group (79.10 ±4.12,4.40 ±0.69),NRG1β strikingly improved cognitive ability ( 67.70 ± 4.90,5.80 ± 0.63 ) and normal cell structure ( t =5.63,4.69,P ＜ 0.05 ).The expressions of NFκB (25.90 ± 6.67 ) reduced while the number of neuronal apoptosis ( 23.50 ± 3.89 ) decreased markablely than those ( 41.10 ±7.95,29.30 ± 7.24) in model group(t =4.63,2.23,P ＜ 0.05).ConclusionNRG1β might decrease the neuronal apoptosis by inhibiting NFκB expressions,so that to improve the learning and memory abilities of experimental dementia rats.

OBJECTIVE： To provi de reference for relevant departments to formulate innovation subsidy policies for pharmaceutical enterprises and enterprises to make their own business strategy decisions. METHODS ：The listed enterprises in China ’s pharmaceutical industry listed before 2012 were selected as the sample enterprises. The annual reports of listed enterprises in pharmaceutical industry and related panel data in CSMAR database during 2012-2019 were colected. Referring to related literatures ， multivariate regression model and threshold model were established to investigate the effects of technology innovation investment ability of sample enterprises ，so as to put forward relevant suggestions. RESULTS & CONCLUSIONS ：A total of 57 sample enterprises were included. The panel data of sample enterprises showed that the technology innovation investment of Chinese pharmaceutical enterprises was basically increasing year by year ，but compared with international standards ，the technology innovation investment of Chinese pharmaceutical enterprises still needed to be improved. The results of multiple regression model showed that the technology innovation investment of pharmaceutical enterprises had no significant impact on their current financial performance and the financial performance of the first and second lags （P＞0.05）. The results of threshold model showed that there was a significant single threshold effect between technology innovation investment and financial performance when enterprise size was taken as the threshold variable （P＜0.05）. When the enterprise size was less than the threshold value of 20.986，the enterprise ’s technology innovation investment had a negative impact on its financial performance （P＜0.05）；when the enterprise size was greater than the threshold value of 20.986，the correlation between the enterprise ’s technology innovation investment and financial performance was not significant （P＜0.05）. It is suggested that China ’s pharmaceutical enterprises should carry out technology innovation activities according to their own strength ，and enterprise managers should formulate different innovation development strategies according to the ac tual situation ，enable enterprises to maintain a reasonable capital structure by broadening financing channels ，identify innovation points according to their own ability ，reduce costs and risks ，and innovate R&D modes，so as to promote the transformation and effective utilization of R&D achievements. Government departments should give full play to the guiding role ，encourage pharmaceutical enterprises to maintain the vitality of R&D and innovation and guide the sustainable innovation and healthy development of the pharmaceutical industry.

A 13-year and 6-month-old girl attended the Hunan Children's Hospital due to delayed menarche. The laboratory test results indicated increased follicle-stimulating hormone and luteinizing hormone, decreased anti-Mullerian hormone, and pelvic ultrasound showed a cord-like uterus and absence of bilateral ovaries. Her 11-year and 5-month-old younger sister had the same laboratory and imaging findings, and both girls were diagnosed with primary ovarian insufficiency. Whole exome sequencing and Sanger sequencing confirmed that the proband and her sister carried heterozygous variants of HROB gene c.718C>T (p.Arg240*) and c.1351C>T (p.Arg451*), which were inherited from their parents respectively and consistent with autosomal recessive inheritance. Oral estradiol valerate at an initial dose of 0.125 mg/d was given to the proband, and the secondary sexual characteristics began to develop after 6 months.
Humans ; Female ; Child ; Infant ; Primary Ovarian Insufficiency/genetics* ; Luteinizing Hormone ; Estradiol

Objective: Conebeam CT (CBCT) was used to measure the palatine between the maxillary first and second molars. The proximal and distal palatal widths of the maxillary first and second molar and the palatal mucosal thickness and bone tissue thickness when microscrew implant anchorage nail were implanted at different angles provided a reference for the clinical selection of microscrew implant placement. Methods: The image data of 90 adult patients were selected as the research object, and the jaw bone was reconstructed by scanning. In maxillary palatine, selection of distances at 12 mm, 14 mm, 16 mm, and 18 mm from the palatal apex of maxillary first molar between the maxillary first and second molar were used as measurement, measured the proximal and distal palatal widths of maxillary first and second molar and the palatal mucosal thickness and bone tissue thickness when microscrew implant anchorage nails were implanted at 30 °, 45 °, 60 °, and 90 °. SPSS 26.0 software was used for one-way ANOVA and LSD pair comparison. Results: The larger the angle of the microscrew implant anchorage nail was, the smaller the proximal and distal medial widths between the maxillary first and second molar, and the difference was statistically significant (P < 0.05). Compared with the 90° direction, the proximal and distal medial widths of the microscrew implant anchorage nail were larger in the 60° direction. The greater the angle of implantation, the smaller the mucosal thickness and the greater the bone tissue thickness, and the results showed a significant difference (P < 0.001). Compared with the direction of 30° and 45°, the mucosal thickness at the direction of 60° was smaller, and the bone tissue thickness was larger. The higher the position of the microscrew implant anchorage nail, the greater the width of the proximal and distal medial, and the difference was statistically significant (P < 0.05). Compared with the positions 12 and 14 mm from the palatal tip, the proximal and distal medial widths of the microscrew implant anchorage nail were larger. The higher the implant position was, the greater the mucosal thickness and the smaller the bone tissue thickness. The results showed a significant difference (P < 0.001). Compared with the position of 18 mm from the palatal tip of the maxillary first molar, the mucosal thickness was smaller and the bone tissue thickness was larger. Conclusion It is most appropriate to implant microscrew implant anchorage nail at least 10 mm in length in the direction of 60° at the palatal apex 16 mm from the maxillary first molar in palatine between the first and second molar.

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.