Sonic Hedgehog (SHH) signaling pathway not only plays key roles in embryonic development,but also functions in postnatal development and maintenance of tissue/organ integrity and function.In recent years,it has been found that the SHH signaling pathway was abnormally activated in some lung diseases,which suggested that the SHH signaling pathway may play a part in the development of some lung diseases.This article reviewed the potential role of SHH signaling pathway on the embryonic lung development and lung diseases.

Objective: To determine human tear proteins using nanoliter liquid chromatography coupled to quadrupole orbitrap mass spectrometry (NanoLC-Q-Orbitrap-MS), and perform a bioinformatics analysis of main proteins. Methods: Human tear samples were collected with capillary, transferred to 3 kDa ultrafiltration tubes containing 400 μL of superpure water and centrifuged at 12 000×g for 15 min. Repeated extraction of tear proteins were performed four times, and following digestion with trypsin, the proteins were separated using the Waters NanoAcquity peptide BEH C18 column (1.7 μm, 100 μm×100 mm) and determined using NanoLC-Q-Orbitrap-MS with the mobile phase of 0.1% formic acid aqueous solution and acetonitrile (0.1% formic acid) in the full MS/dd-MS2 mode. The types of proteins were characterized in the Uniprot database using the software Proteome Discoverer version 2.1 and verified using bovine serum albumin. The tear proteins were subjected to gene annotation analysis using the String database. Results: A total of (387±160) human tear proteins were yielded, with a relative standard deviation (RSD) of 4.13%, and there were 25 types of proteins with a relative high abundance, including lipocalin 1, lysozyme and lactoferrin. The peptide sequence coverage of bovine serum albumin was (86.08±2.61)%, with a RSD of 3.03%. The 25 major tear proteins were involved in substance transduction among cells, homeostasis process, negative regulation of the endopeptidase activity, detection of chemical stimulants and humoral immune responses, and the 16 proteins had close interactions. Lacritin, lipocalin 1, lactoferrin, lysozyme and zinc-α 2-glycoprotein, which had a relative high abundance, had close biological connections. Conclusion NanoLC-Q-Orbitrap-MS is stable, reliable and feasible for detection of multiple proteins in tears.

Objective To understand the application and effect of problem based,case based and evidence based (PCE) combined teaching method in urology surgery clinical teaching.Methods A total of 50 clinical medicine students were selected.PCE combined teaching method was applied in urology surgery clinical teaching and the teaching effect was evaluated.Results The ratios of student who thought PCE combined teaching method could stimulate learning enthusiasm,improve learning efficiency and improve the abilities of logical thinking,inductive analysis,practical application,self-study,literature retrieval,innovation and team cooperation were 96％,94％,95％,94％,100％,88％,100％,96％ and 95％ respectively.All students thought this new teaching method could be extended in other subjects.Conclusions Application of PCE combined teaching method in urology surgery clinical teaching can achieve good teaching effect and it is worth recommending in clinical teaching.

Objective To explore the curative effect of clinical application of modified McBride's procedure on correcting mild-moderate hallux valgus.Methods We had retrospectively assessed 32 patients(52 feet)treated with the procedure of modified McBride's procedure.All patients were followed up,the follow -up period from 6 months to 6 years(3.1 years on average).There were 2 male(4 feet)patients and 30 female(48 feet)patients in this group.The average age at the time of surgery was 41.6 years old(from 21 to 59 years).Results According to the forefoot score of American Orthopedics Foot and Ankle Society(AOFAS),29 feet(55.8%)were excellent,17 feet (32.7%)were good,And the rate of excellent and good was 88.5%.The average correction of HVA and IMA was 13.68°and 3.24°respectively compared with the preoperative cases.Conclusion This procedure can not only effec-tively reduce the increased hallux valgus angle,but also narrow the angle between the 1st and 2nd metatarsal,relocate the sesamoid system,and effectively relieve patients'pain.This approach is of minor side effects to bone and joint structure,and of rapid recovery.It is a preferential choice to treat mild-to-moderate hallux valgus deformity.

Directive 2004/24/EC of the European Parliament and the Council entered into force on April 30th, 2004. After 7 years, there is no Chinese medicine to be registered successfully in European market as traditional herbal medicinal products. The thesis gives some ideas to tackle this problem. Procedure for the Preparation of Community Monographs for Traditional Herbal Medicinal Products (EMEA/HMPC/182320/2005) published by European Medicines Agency is an important guidance for traditional herbal products to enter European Community monographs. The thesis introduces and details the procedure as well as gives feasible suggestions about the procedure. It suggests that Chinese medicines enter European Community monographs first, and then apply the registration according to the directive 2004/24/EC. This is an easier access to European market.

Objective To analyze the relationship of cerebral microbleeds (CMBs)of different regions,especially mixed-CMBs,with cerebral amyloid angiopathy (CAA)detected using 18F-AV45 positron emission tomography(PET).Methods A total of 52 consecutive patients (68.17 ± 9.89 years old)with memory decline and CMBs found in susceptibility-weighted images(SWI)according to the inclusive and exclusive criteria were recruited.Patients were divided into three groups based on different regions of CMBs,the strictly lobar CMBs (SL-CMBs) group,the deep-CMBs (D-CMBs) group and the mixed-CMBs (M-CMBs)group.Patients in the three groups underwent 18F-AV45 PET detection and then were analyzed based on the results of 18F-AV45 PET.Results The positive rates of cerebral amyloid angiopathy in the SL-CMBs,M-CMBs and D-CMBs groups were 68.4 ％ (13/19),82.4 ％ (14/17) and 25.0 ％ (4/16),respectively,with statistical significance (P =0.002).There were significant differences in positive rates of cerebral amyloid angiopathy between the D-CMBs group and the M-CMBs group and between the D-CMBs group and the SL-CMBs group(P =0.001 and 0.010,respectively),while there was no difference between the M-CMBs and SL-CMBs groups in positive rates of cerebral amyloid angiopathy(P =0.335).Using the D-CMBs group as the reference group,multivariate logistic regression analysis showed that the odds ratios of positive CCA detected by PET in SL-CMBs and M-CMBs were 30.585(95％CI:2.492-375.360)and 8.107(95％CI:1.072-61.295),respectively.Conclusions Compared with D-CMBs,M-CMBs and SL-CMBs are more likely to be related to cerebral amyloid angiopathy.The presence of M-CMBs also indicates that patients have a high probability of CAA.

Objective:To conduct a glucagon like peptide-1(GLP-1)controllability model rat by chemical genetics, and observe the impact of GLP-1 neuron excitability on appetite.Methods:Fifteen rats were evenly divided into Green fluorescent protein(GFP)group, HM3D group, and HM4D group. Various combinations of adeno-associated virus(rAAV)were injected into the nucleus tractus solitarius(NTS). rAAV-GLP-1-cre and rAAV-GFP-dio were administered in rats of GFP group. The rats of HM3D group were injected with rAAV-GLP-1-cre and rAAV-HM3D-mCherry-dio while rAAV-GLP-1-cre and rAAV-HM4D-mCherry-dio were injected in rats of HM4D group . The optimal dose of clozapine N-oxide(CNO)was selected based on feeding behavior and body weight changes of rats after intraperitoneal injection of different doses of CNO. The controllability of GLP-1 neurons was confirmed by comparing with intraperitoneal injection of saline. The number of activated GLP-1 neurons in the NTS area and the expression of POMC neurons in the hypothalamus were detected 30 minutes after CNO injection.Results:GLP-1 neurons in the NTS area of rats were successfully labeled. The rat of HM3D group revealed a decrease in food intake( P=0.021)while the rat of HM4D group showed an increase( P=0.002), when given 1 mg/kg of CNO, no changes at the dose of 0.5 mg/kg and 3.0 mg/kg. Immunofluorescence showed that the activity of GLP-1 neurons in NTS of GFP group was lower than that of HM3D group( P=0.022), and higher compared with that of the HM4D group( P=0.049). The expression of GLP-1 neurons in NTS and POMC neurons in the hypothalamus of the HM3D group after intraperitoneal injection of CNO was also higher than that in the HM4D group( P=0.003). Conclusion:Using chemical genetics technology, GLP-1 controllability model rat could be successfully established via injecting varying combinations of rAAV into the NTS area of rat. Injection of 1 mg/kg CNO can effectively activate or inhibit the neuron to regulate appetite.

Objective:To analyze the characteristics of the apolipoprotein E(Apo E)genotype and cognitive impairment in patients with cerebral microbleeds(CMBs)and positive β-amyloid(Aβ)by using [18F]-AV45 positron emission tomography(PET).Methods:From September 2015 to May 2018, 152 patients with cognitive impairment and CMBs on the susceptibility-weighted imaging(SWI)sequence of head MRI at the neurology department of our hospital, assessed by mini-mental status examination(MMSE)score ≤26 and Montreal cognitive assessment(MoCA)≤25, were consecutively recruited in this retrospective study.After assessment with the inclusion and exclusion criteria, 69 patients aged 68.8±9.3 years were considered eligible for further analysis.Patients were divided into the Aβ-positive group(Aβ + Group, n=37)and the Aβ-negative group(Aβ -Group, n=32)after cognitive assessment, ApoE genotyping and [18F]-AV45 PET examination.Twenty-one healthy elderly controls(HC Group)who took health examination during the same period were enrolled.The results of cognitive assessment and Apo E genotyping were compared between the three groups. Results:The positive rate of the ApoE ε4 allele was 35.6%(32/90), 56.8%(21/37), 18.8%(6/32), and 23.9%(5/21)in the Aβ + , Aβ -and HC groups, respectively, with statistical significant differences between the groups( χ2=12.467, P<0.01). There were significant differences in the positive rate of the ApoE ε4 allele between the Aβ + and HC groups and between the Aβ + and Aβ -groups( χ2=5.880 and 10.407, P<0.05 and P<0.01). The percentage of patients with deep cerebral microbleeds was higher(56.3% or 18/32 vs.8.1% or 3/37, χ2=18.784, P<0.01)and of patients with lobar hemorrhage was lower(12.5% or 4/32 vs.45.9% or 17/37, χ2=9.066, P<0.01)in the Aβ -group than in the Aβ + group, while there was no significant difference in the percentage of patients with mixed cerebral microbleeds between the Aβ -and Aβ + groups( χ2=1.556, P>0.05). There were significant differences in cognitive function between the Aβ + and HC groups, in memory, executive function, visuospatial ability and language between the Aβ + and Aβ -groups, and in executive function, visuospatial ability and attention between the Aβ -and HC groups. Conclusions:Cognitive impairment is more extensive and severe in CMBs patients with Aβ deposition and is associated with positive ApoE ε4.

Clinical decision support system is a system that utilizes models or knowledge bases to assist clinical decision-making through human-computer interaction for semi-structured or unstructured clinical problems, with the aim of reducing decision-making errors among medical staff and improving the quality of medical and nursing services. In recent years, clinical decision support system has attracted wide attention in the field of clinical nursing of Traditional Chinese Medicine. This paper will review the development status, application advantages and existing problems of clinical decision support system in the field of clinical nursing of Traditional Chinese Medicine, aiming to provide reference for the development of a more specialized and systematic clinical decision support system for clinical nursing of Traditional Chinese Medicine.