There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

In recent years, the subthreshold micropulse laser is a kind of laser mode which is characterized by long intermittence. It achieves effective therapeutic effect while minimizes the damage to tissues. At present, it has been used to treat diabetic macular edema. Early studies suggested that the laser selectively acts on retinal pigment epithelial cells to reduce macular edema by regulating the expression of inflammatory biomarkers, growth factors, heat shock proteins and other substances. In recent years, with the development of research, more and more emphasis has been placed on the role of retinal glial cells. Müller cells are also considered as one of the target cells affected by micropulse laser, but there is no evidence of direct or indirect effects of micropulse laser on Müller cells. In the near future, it is expected that we will have more clinical evidence to confirm the target cells of the micropulse laser, which may be further confirmed by in vitro experiments through Müller cells or Müller cells co-cultured with retina pigment epithelium cells, so as to make a more detailed statement on the mechanism of it.

Objective:To compare the sedative and anti-anxiety effects of levo-tetrahydropalmatine (L-THP) and diazepam on conditioned fear model rats.Methods:According to the random number table method, 32 adult male rats were divided into blank group, model group, diazepam group and L-THP group(with 8 rats in each group). The conditioned fear model was reproduced by the plantar electric shock method. Four days after the modeling, the rats in diazepam group and L-THP group were given diazepam (3.6 mg/kg) and L-THP (25 mg/kg) were respectively gavaged once a day for 10 days, the rats in blank group and model group were given the same volume of saline. After the administration, the elevated plus maze test and the open field test were used to measure the anxiety behavior of the rats, and the sleep energy monitoring system was used to detect changes in sleep and energy-related indicators. SPSS 23.0 and Graphpad Prism 7.0 softwares were used for data analysis, multiple samples between groups were compared by one-way ANOVA, and LSD test was used for pairwise comparison.Results:The results of the elevated plus maze experiment showed that compared with the model group, the percentage of open-arm entry times ((11.27±8.78)%, (30.11±14.59)%, P<0.05) and the percentage of open-arm residence time ((1.94±1.48)%, (17.53±8.21)%, P<0.05) in diazepam group were all significantly increased. Compared with the model group, the open arm residence time, the percentage of open arm residence time and the percentage of open arm entry times in L-THP group showed an upward trend, but there was no statistical significance (all P>0.05). The results of the open field experiment showed that compared with the model group, the time of entering the central grid ((2.99±1.83) s, (6.94±3.52) s, P<0.05) and the time of entering the peripheral field ((297.01±1.83) s, (293.30±3.52) s, P<0.05) in diazepam group both increased. Compared with the model group, there was no significant difference in the changes of various indexes in L-THP group (all P>0.05). The results of locomotor activities showed that the autonomic activity times of model group in nighttime was significantly lower than that of blank group((758.79±375.37)times/h, (1 101.93±525.96)times/h, P<0.05). Compared with the model group, the number of autonomous activities of rats in L-THP group in daytime ((820.57±364.60) times/min, (502.40±228.54)times/min, P<0.05) decreased, and the number of autonomous activities in the nighttime ((758.79±375.37) times/min, (1 146.85±309.69)times/min, P<0.05) increased, but there was no significant change in the number of autonomous activities in the whole day. Correlation analysis of energy metabolism related indexes and sleep time of rats in each group were analyzed. The experimental results showed that the daytime sleep time were negatively correlated with heat value ( r=-0.335, P<0.05), and the night sleep time was positively correlated with daytime heat value ( r=0.352, P<0.05). Conclusion:L-tetrahydropalmatine has no significant anti-anxiety effect in the concentration range used in this study, but its sedative and improving sleep activity rhythm are better than diazepam.

Objective:To observe the relationship between the response to anti-vascular endothelial growth factor (VEGF) drug treatment and single nucleotide polymorphism (SNP) genotype in patients with wet age-related macular degeneration (wAMD).Methods:A retrospective clinical study. From August 2019 to September 2020, 103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 59 males (57.28%, 59/103) and 44 females (42.72%, 44/103); the average age was 68.74±7.74 years. The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. Optical coherence tomography was used to detect the central retinal thickness (CRT) of the affected eye. At the same time, the patient's high-density lipoprotein cholesterol (HDL-C) was tested. All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months. Before the initial treatment, peripheral venous blood from the patient were collected. Interleukin-8 ( IL-8), complement C3 gene ( C3), complement factor H ( CFH), liver lipase ( LIPC), cholesterol ester transfer protein ( CETP), ATP binding cassette subfamily a member 1 ( ABCA1), lipoprotein lipase ( LPL), fatty acid desaturation gene cluster ( FADS1) SNP. According to gene frequency, genotypes are divided into wild type and mutant type were detected. Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test. Results:There were fewer CRT responders in IL-8 rs4073 mutant (TA+AA) patients than wild-type (TT) [odds ratio ( OR)=0.310, 95% confidence interval ( CI) 0.106-0.910, P<0.05). Among them, after the drug stratification test, the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders ( OR=0.179, 95% CI=0.034-0.960, P=0.033). Patients with LIPC rs2043085 mutant (CT+TT) with BCVA increased ≥0.2 logMAR are more likely than wild-type (CC) ( OR=3.031, 95% CI 1.036-8.867, P<0.05); HDL-C level was significantly lower Compared with wild type (CC), the difference was statistically significant ( t=2.448, P=0.016). There was no significant difference in logMAR BCVA and CRT between IL-8 rs4073, LIPC rs2043085 mutant and wild-type patients before treatment ( IL-8 rs4073: Z=-0.198, -1.651; P=0.843, 0.099; LIPC rs2043085: Z=-0.532, -0.152; P=0.595, 0.879). C3 rs 225066, CFH rs800292, CETP rs708272, ABCA1 rs1883025, FADS1 rs174547, LPL rs12678919 have no correlation with anti-VEGF drug treatment response. Conclusions:Patients with wAMD are treated with anti-VEGF drugs. Those with IL-8 rs4073 locus A genotype may be less responsive to CRT. LIPC rs2043085 locus T genotypes may be relatively more responsive to BCVA.

Objective:To explore the early warning of blood growth differentiation factor-15 (GDF15) as a new stress indicator.Methods:A total of 53 armed police soldiers selected to participate in high-intensity training, measuring the soldiers' serum GDF15, high-sensitivity C-reactive protein (S-CRP), and C-reactive protein (CRP) before and after the high-intensity training , Interleukin-6 (IL-6), Procalcitonin (PCT) levels, compare the coefficient of variation of each index; use SPSS 24 software for statistical analysis, measurement data are expressed as mean ± standard deviation (Mean±SD), The comparison of measurement data adopts group t test. Results:The GDF15 level of fighters after high-intensity training was (176.28±97.45) pg/mL, which was higher than (120.35±69.87) pg/mL before high-intensity training. The difference was very significant ( P <0.001). After high-intensity training, IL-6 and CRP levels were lower than before high-intensity training, the difference was statistically significant ( P<0.05); there was no statistically significant difference in S-CRP and PCT before and after high-intensity training ( P>0.05). The coefficient of variation of GDF15 index is smaller than S-CRP, CRP, IL-6, PCT. Conclusion:Blood growth differentiation factor-15 (GDF15) is of great significance in warning the stress state after high-intensity training. It has higher sensitivity than other conventional stress indicators like S-CRP, CRP, IL-6 and PCT.

Objective:To explore the value of growth differentiation factor 15 (GDF15) in the early diagnosis of acute chest pain.Methods:A total of 96 patients with acute chest pain admitted to the Emergency Department of Hainan Hospital of PLA General Hospital from January to November 2020 were retrospectively collected. The sex, age, troponin T, creatine kinase, creatine kinase isoenzyme, GDF15 and B-type natriuretic peptide of patients within 30 min after admission were recorded, and the differences of each index in different groups were compared. ROC curve was drawn to evaluate the diagnostic value of GDF15 and TNT/BNP in acute coronary syndrome (ACS). The Gensini score, left ventricular ejection fraction, length of stay in hospital and the number of stents were calculated, and the correlation between these indexes and GDF15 concentration was evaluated.Results:The general trend of acute chest pain was more male than female (72.92% vs. 27.08%) , the oldest group was the UA group (64.67 ± 13.87) years old , the youngest group was cardiac arrest group (47.29 ± 9.99) years old . There were higher rates of hypertension in the STEMI group, NSTEMI group and UA group, and none of the groups showed significant advantage in diabetes. The GDF15 concentration was higher in ACS related chest pain group [(2.360 ± 1.710) ng/mL vs. (1.380 ± 1.040) ng/mL, P<0.01]. The area under the Receiver Operating Characteristic Curve (AUC) of GDF15 combined with TNT was up to 0.863. GDF15 concentration was negatively correlated with ejection fraction, positively correlated with Gensini score, positively correlated with the number of stents implanted, and positively correlated with the length of hospital stay. Conclusions:GDF15 is valuable in the diagnosis and prognosis of acute chest pain. The combination of GDF15 and TNT can improve the diagnostic rate of ACS.

Objective:To investigate the current situation of the implementation of breastfeeding in the state of mother infant separation in 75 hospitals in China, based on the evidence-based guidelines for breastfeeding of hospitalized newborns (hereinafter referred to as the guidelines).Methods:Totally 75 hospitals in China were selected using the convenience sampling method to distribute questionnaires to compare the implementation of breastfeeding after separation of mother and infant.Results:All the hospitals selected in this survey were not satisfied with the overall implementation of the guide, but the general hospital's interpretation and learning of the guide was better than that of the specialized hospital, with a statistically significant difference ( χ2 value was 5.616, P <0.05); the breastfeeding rate was lower after the separation of mother and infant, and only 18.7% (14/75) of the units with the feeding rate ≥ 75%; they provided support related to breast milk collection, kangaroo nursing and professional professionals in the aspect of quality management, specialized hospital was better than general hospital, the difference was statistically significant ( χ2 values were 9.450, 10.516, 6.436, P<0.05); 62.1% (18/29) of the specialized hospitals have multi-disciplinary cooperation teams to promote the separation of mother and infant breastfeeding, while only 34.8% (16/46) of the comprehensive hospitals have multi-disciplinary cooperation teams , the difference was statistically significant ( χ2 value was 7.254, P<0.05). Conclusion:The evidence-based guidelines for breastfeeding of hospitalized newborns in China mostly refer to the relevant international standards. There are some difficulties in the implementation of the guidelines due to the large differences in the economy and policies of various regions in China. In order to improve the success rate of breastfeeding separation between mother and infant, China should establish a national standard that is in line with the national conditions, so as to facilitate the reference implementation of hospitals at all levels.

Objective:With the help of computed tomographic angiography and three dimensional technique, to explore to clinical application of the free scapular flap.Methods:From January 2013 to June 2018, 21 cases of deep post-burn wounds of limbs were repaired with free scapular flaps. 3D-CTA examinations were performed before operation, and the personalized reconstructions were designed according to different shape and size of the defects in the recipient sites. The outcome, color, texture, scar contracture and dysfunction of the flaps were observed.Results:The 3D-CTA technique was able to define the anatomical structure of the donor and recipient area before the operation. During the operation, it was found that the course and distribution of blood vessels were basically consistent with the design before the operation. 21 flaps survived after the operation. During the follow-up of half a year to one year, the color, texture, and appearance of the flap recovered satisfactorily, the function of the affected limb activity recovered, no obvious scar hyperplasia was found in the dorsal donor area, and the function of the shoulder joint was normal.Conclusions:The free scapular flap is one of the ideal methods to repair the deep burn wounds of limbs, which has reliable blood supply, wide range of incision, convenient operation, no damage to the main blood vessels and concealed donor areas. 3D-CTA examination before operation guided the design and implementation of operation scheme, which improved the accuracy of intraoperative vascular anastomosis.

Objective:With the help of computed tomographic angiography and three dimensional technique, to explore to clinical application of the free scapular flap.Methods:From January 2013 to June 2018, 21 cases of deep post-burn wounds of limbs were repaired with free scapular flaps. 3D-CTA examinations were performed before operation, and the personalized reconstructions were designed according to different shape and size of the defects in the recipient sites. The outcome, color, texture, scar contracture and dysfunction of the flaps were observed.Results:The 3D-CTA technique was able to define the anatomical structure of the donor and recipient area before the operation. During the operation, it was found that the course and distribution of blood vessels were basically consistent with the design before the operation. 21 flaps survived after the operation. During the follow-up of half a year to one year, the color, texture, and appearance of the flap recovered satisfactorily, the function of the affected limb activity recovered, no obvious scar hyperplasia was found in the dorsal donor area, and the function of the shoulder joint was normal.Conclusions:The free scapular flap is one of the ideal methods to repair the deep burn wounds of limbs, which has reliable blood supply, wide range of incision, convenient operation, no damage to the main blood vessels and concealed donor areas. 3D-CTA examination before operation guided the design and implementation of operation scheme, which improved the accuracy of intraoperative vascular anastomosis.

AIM To investigate the effects of ethyl acetate extract from Huangqi Injection (HQIEACE) on leucopenia mice.METHODS An experimental mouse model of leucopenia was induced by cyclophosphamide.NMR based metabolomic profiling technique coupled with multivariate statistical method was used for performing metabolomic analysis.RESULTS HQIEACE could elevate the levels of white blood cell,monocytes,neutrophils and lymphocyte in modeled mice.The levels of ten potential endogenous metabolites (lipid,leucine,3-D-hydroxybutyrate,lactate,alanine,pyruvate,creatine,scyllo-inositol,betaine and glucose) were reversed.CONCLUSION The metabolic pathways related to the pharmacological effects of HQIEACE on leucopenia are probably involved in body energy metabolism,amino acid metabolism,oxidative stress and choline metabolism.