Glucagon and its analogues are a intestinal stimulating insulin screened by the small intestinal L cells. It can smoothly penetrate the blood-brain barrier into the brain tissue and play a neuropro-tective role. Liraglutide and glucagon and its analogues have higher homology. After entering the brain tissue, it is able to bind with the related receptors and activates Nrf2/HO-1 signaling pathway and thus reducing the production of oxidative stress products, increases the glutathione, heme oxygen synthase, superoxide dismutase and other phase Ⅱ detoxification enzymes, promotes angiogenesis, and protects the nerve cells of diabetes combined with cerebral ischemia injury.

ObjectiveToinvestigatetheprotectiveeffectandmechanismofscutelarincombinedwith paeoniflorin after permanent cerebral ischemia in rats. Methods Forty-eight adult male SD rats w ere randomly divided into four groups: sham-operation, cerebral ischemia, scutelarin+ paeoniflorin, and cyclopamine (n=12 in each group). A model of permanent middle cerebral artery occlusion w as induced by suture method. The intraperitoneal injection of cyclopamine 6 mg/kg, a specific inhibitor of sonic hedgehog (SHH) pathw ay, at 15 min before ischemia in the cyclopamine group, w hile other groups w ere intraperitoneal y injected an equal volume of saline. At 0 hour and 3 hours after ischemia, the scutel arin+paeoniflorin group and cyclopamine group w ere intraperitoneal y injected scutel arin ( 20 mg/kg ) and paeoniflorin (30 mg/kg), while other groups were intraperitonealy injected an equal volume of saline. Neurological deficit scores w ere performed at 24 hours after ischemia, and then the rats w ere decapitated. The cerebral infarct volume w as measured by using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Real-time fluorescent quantitative polymerase chain reaction and Western blotting w ere used respectively to detect the expression levels of SHH, Patched-1, Gli-1 mRNAs and proteins in the ischemic cortex. Results The neurological deficit scores in the cerebral ischemia group, scutel arin+paeoniflorin group, and cyclopamine group w ere 3.33 ±0.52, 1.50 ±0.55, and 3.67 ±0.52, respectively. The neurological deficit score in the scutel arin+paeoniflorin group w as significantly low er than that in the cerebral ischemia group ( P<0.05), and the neurological deficit score in the cyclopamine group w as significantly higher than that in the scutelarin+paeoniflorin group ( P<0.05). The infarct volume percentage in the cerebral ischemia group, scutelarin+paeoniflorin group, and cyclopamine group were 31.77%±1.19%, 22.94%±2.65%, and 35.53%±0.20%, respectively. The infarct volume in the scutel arin+paeoniflorin group w as significantly less than that in the cerebral ischemia group ( P<0.05), and the infarct volume in the cyclopamine group was significantly larger than that of the scutelarin+paeoniflorin group (P<0.05). The expression levels of SHH, Patched-1, Gli-1 mRNAs and proteins in the cerebral ischemia group, scutelarin+paeoniflorin group, and cyclopamine group w ere significantly higher than those in the sham -operation group (al P<0.05). The expression levels of SHH, Patched-1, Gli-1 mRNAs and proteins in the scutelarin+paeoniflorin group were significantly higher than those in the in the cerebral ischemia group (al P<0.05), and the expression levels of Gli-1 mRNA and protein in the cyclopamine group were significantly lower than those in the scutelarin+paeoniflorin group ( al P<0.05 ). Conclusions The scutel arin combined w ith paeoniflorin has certain protective effect on focal cerebral ischemia injury in rats. Its mechanism is associated w ith the activation of SHH signaling pathw ay.

Objective To investigate the effect of expressions of endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in the ischemic cortex on ischemic cerebral injury in rats with diabetes mellitus.Methods A total of 36 healthy male Sprague-Dawley rats were divided into 3 groups:a shamoperation group,a cerebral ischemic group,and a diabetic cerebral ischemic group according to the random number table method.A diabetes model was induced by injection of streptozocin,and then,a permanent focal cerebral ischemic model was induced by the suture method.At 24 h after ischemia,the neurological deficit scores were conducted.The triphenyl tetrazolium chloride staining was used to measure the infarct volume.TUNEL was used to detect the apoptotic cells.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of VEGF and VEGFR2 mRNAs.Western blot was used to detect the expression levels of VEGF and VEGFR2 proteins.Results In the sham operation group,there were no neurological deficit and infarcts,and there were only a few apoptotic cells and a few expressions of VEGF,VEGFR2 mRNAs and protein.The neurological function score (4.25 ±0.54 vs.2.86 ±0.73);t =5.303,P＜0.001),infarct volume (51.69 ±2.26 mm3 vs.30.15 ±2.08 mm3;t =23.166,P＜0.001),and the number of apoptotic cells (24.22 ± 1.34/HP vs.13.28 ±0.37/HP;t =27.261,P＜0.001) in the diabetic cerebral ischernia group were significantly increased than those in the cerebral ischemic group,while VEGF,VEGFR2 mRNA,and protein expression level were significantly decerased (VEGF mRNA:4.74 ± 0.54 vs.6.71 ± 0.91,P ＜ 0.001;VEGFR2 mRNA:4.06 ± 0.60 vs.6.16 ± 0.96,P ＜ 0.001,VEGF protein:0.99 ± 0.13 vs.1.55 ± 0.23,P ＜ 0.001;VEGFR2 protein:4.12 ± 0.74 vs.6.23 ± 0.76,P ＜ 0.001) compare with the cerebral ischemic group.Conclusions VEGF/VEGFR2 signal pathway participates in diabetes aggravating ischemic cerebral injury.The downregulating of VEGF/VEGFR2 may be one of the mechanisms of diabetes aggravating ischemic cerebral injury.

Nanotechnology is the technique that is used in manufacturing special function products with the studies of movement regularities and properties for electrons, atoms and molecules within 1-100 nm. It is penetrating into the fields of biology and medicine. Because nanoparticles possess quantum size effect, surface little size effect and grand quantum tunnel effect, they exhibit many characteristics such as great specific surface area, high surface activity, a lot of surface active centers, high catalytic efficiency and strong adsorbing ability. The development of biology and medicine will be speeded up with the progress of nanotechnology and the understanding of nanoparticles.
Biomedical Technology ; Humans ; Medicine ; trends ; Nanotechnology ; Nanotubes ; chemistry ; Particle Size

Objective:To study the change in serum fibroblast growth factor 21(FGF21)level and its correlation with liver functions in elderly patients with hepatitis B virus(HBV)-related cirrhosis.Methods:A total of 150 elderly patients with HBV infection admitted to Beijing Ditan Hospital and China-Japan Friendship Hospital from January 2019 to December 2020 were selected and divided into chronic hepatitis B(CHB)group(n=70)and HBV-related cirrhosis group(n=80). Healthy subjects were selected as the control group(n=50). Serum FGF21 was determined by ELISA method.Clinical data, clinical laboratory indicators and FGF21 as a core parameter of this study were collected and compared among control group, CHB group, HBV-related cirrhosis group.The correlations of FGF21 level with several liver function indexes were analyzed by Pearson correlation analysis.Results:The levels of total bilirubin(TBil)and total biliary acid(TBA)were significantly higher in HBV-related cirrhosis group than in CHB group.The levels of aspartate transaminase(AST), alanine transaminase(ALT), glutamyl transpeptadase(GGT), serum albumin, cholinesterase, FGF21 and HBV-DNA were significantly lower in HBV-related cirrhosis group than in CHB group(all P<0.05). The levels of serum FGF21 were(108.6 ± 7.3)ng/L, (92.5 ± 7.6)ng/L and(75.8 ± 6.3)ng/L in Child-Pugh A, B and C patients, respectively.The level of FGF21 was statistically significantly decreased with the increase of Child-Pugh grading( F=18.290, P=0.000). Serum FGF21 level was positively correlated with AST, ALT, TBil, cholin-esterase and albumin levels( r=0.652, 0.579, 0.609, 0.558, 0.613, all P<0.05). Conclusions:The level of serum FGF21 is significantly decreased in elderly patients with HBV-related cirrhosis, and is positively correlated with liver function indexes.

Objective:To evaluate the safety and efficacy of metal clips combined with endoscopic histoacryl injection for gastric varices with spontaneous portosystemic shunts.Methods:The clinical data and complications of 32 patients who were treated with metal clips combined with endoscopic histoacryl injection at Beijing Ditan Hospital of Capital Medical University from May 2016 to October 2018 were collected and analyzed.Results:Hemostasis was achieved in all patients, and the median volume of histoacryl was 3.8 mL. Varices were eradicated or disappeared in 9 cases, and the degree of varices were lessened in 23 cases. No rebleeding was found at 72 h, 7 d, 14 d and 6 weeks after operation in any patient. No ectopic embolism occurred.Conclusion:Metal clips combined with endoscopic histoacryl injection is effective and safe to treat gastric varices with spontaneous portosystemic shunts.

Objective To evaluate the efficacy of 0. 3％ sodium hyaluronate ophthalmic solution in mild.to. moderate dry eye patients. Methods A prospective,multicenter,and self.controlled clinical trial was performed on 200 patients who were diagnosed as mild.to.moderate dry eye from January 2015 to June 2017 in Eye Institute of Xiamen University,Eye &ENT Hospital of Fudan University,Zhongshan Ophthalmic Center,Xiangya Hospital Central South University, Eye Hospital of Wenzhou Medical University, and Beijing Tongren Hospital, Capital Medical University. The study protocol was approved by the Ethics Committees of Eye Institute of Xiamen University,written informed consent was obtained from each patient prior to any medical examination. All patients were treated with 0. 3％ sodium hyaluronate ophthalmic solution 6 times per day ( one drop each time) for 28 days. Corneal fluorescein sodium staining,tear film break.up time (BUT),SchirmerⅠtest (SⅠt),degree of conjunctival hyperemia,eyelid margin,meibomian gland secretion,secretory capacity of meibomian gland and subjective symptoms were assessed at baseline,on the 14th day and 28th day after treatment. Bulbar impression cytology was evaluated at baseline and on the 28th day after treatment. Irritation of 0. 3％ sodium hyaluronate ophthalmic solution was estimated on the 14th day and 28th day after treatment. Results The total score of subjective symptoms,BUT,SⅠt,degree of conjunctival hyperemia were significantly different among different treatment time points( F=108. 969,27. 598,16. 838,36. 750;all at P<0. 01). Compared with before treatment,the total score of subjective symptoms was significantly decreased, the degree of conjunctival hyperemia and the total corneal fluorescein sodium staining point number were significant decreased on the 14th day and 28th day after treatment. The total score of subjective symptoms,degree of conjunctival hyperemia and total corneal fluorescein sodium staining point number on the 28th day after treatment were significant lower than those on the 14th day after treatment. Compared with before treatment,the BUT was significantly longer and the SⅠt scores were significantly increased on the 14th day and 28th day after treatment. The BUT on the 28th day after treatment was significantly longer than that on the 14th day after treatment;no significant difference in SⅠt was observed between the 28th day and the 14th day after treatment. The scores of palpebral margin change,meibomian gland secretory ability and secretion characteristics were not significantly different among different treatment time points(H=0. 255,2. 356,0. 294;all at P>0. 05). The impression cytology grade on the 28th day after treatment was 1. 08±0. 74,which was significantly lower than 1. 53±0. 76 before treatment (t=5. 979, P<0. 01). The number of goblet cells on the 28th day after treatment was significantly higher than that before treatment(U=1806. 500,P<0. 01). On the 14th day after treatment,70％ of the patients indicated that the drug was non.irritating,and no patient had intolerable irritation affecting daily lives. All patients had good tolerance to this drug. Conclusions The use of 0. 3％ sodium hyaluronate eye drops can improve the symptoms and signs of mild to moderate dry eye,which can be widely used for mild.to.moderate dry eye patients in clinic.

Objective To evaluate the efficacy of 0.3％ sodium hyaluronate ophthalmic solution in mild-to-moderate dry eye patients.Metbods A prospective,multicenter,and self-controlled clinical trial was performed on 200 patients who were diagnosed as mild-to-moderate dry eye from January 2015 to June 2017 in Eye Institute of Xiamen University,Eye & ENT Hospital of Fudan University,Zhongshan Ophthalmic Center,Xiangya Hospital Central South University,Eye Hospital of Wenzhou Medical University,and Beijing Tongren Hospital,Capital Medical University.The study protocol was approved by the Ethics Committees of Eye Institute of Xiamen University,written informed consent was obtained from each patient prior to any medical examination.All patients were treated with 0.3％ sodium hyaluronate ophthalmic solution 6 times per day (one drop each time) for 28 days.Corneal fluorescein sodium staining,tear film break-up time (BUT),Schirmer Ⅰ test (S Ⅰ t),degree of conjunctival hyperemia,eyelid margin,meibomian gland secretion,secretory capacity of meibomian gland and subjective symptoms were assessed at baseline,on the 14th day and 28th day after treatment.Bulbar impression cytology was evaluated at baseline and on the 28th day after treatment.Irritation of 0.3％ sodium hyaluronate ophthalmic solution was estimated on the 14th day and 28th day after treatment.Results The total score of subjective symptoms,BUT,S Ⅰ t,degree of conjunctival hyperemia were significantly different among different treatment time points (F =108.969,27.598,16.838,36.750;all at P＜0.01).Compared with before treatment,the total score of subjective symptoms was significantly decreased,the degree of conjunctival hyperemia and the total corneal fluorescein sodium staining point number were significant decreased on the 14th day and 28th day after treatment.The total score of subjective symptoms,degree of conjunctival hyperemia and total corneal fluorescein sodium staining point number on the 28th day after treatment were significant lower than those on the 14th day after treatment.Compared with before treatment,the BUT was significantly longer and the S Ⅰ t scores were significantly increased on the 14th day and 28th day after treatment.The BUT on the 28th day after treatment was significantly longer than that on the 14th day after treatment;no significant difference in S Ⅰ t was observed between the 28th day and the 14th day after treatment.The scores of palpebral margin change,meibomian gland secretory ability and secretion characteristics were not significantly different among different treatment time points(H=0.255,2.356,0.294;all at P＞0.05).The impression cytology grade on the 28th day after treatment was 1.08±0.74,which was significantly lower than 1.53±0.76 before treatment (t =5.979,P＜0.01).The number of goblet cells on the 28th day after treatment was significantly higher than that before treatment (U =1 806.500,P＜ 0.01).On the 14th day after treatment,70％ of the patients indicated that the drug was non-irritating,and no patient had intolerable irritation affecting daily lives.All patients had good tolerance to this drug.Conclusions The use of 0.3％ sodium hyaluronate eye drops can improve the symptoms and signs of mild to moderate dry eye,which can be widely used for mild-to-moderate dry eye patients in clinic.

Objective:To analyze the clinical manifestations and signs of the first diagnosed dry eye patients, and to explore the concordance between the Chinese dry eye diagnostic criteria and the Asian dry eye diagnostic criteria.Methods:A cross-sectional multicenter study was conducted.One hundred and forty-one eyes of 141 patients who were diagnosed as dry eye for the first time were included in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Putuo District Center Hospital from December 2016 to May 2018.All patients completed the Chinese Dry Eye Questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) to evaluate the symptoms of dry eye.Tear film breakup time (BUT), keratoconjunctival fluorescein staining, meibomian gland morphology and function examination, and Schirmer Ⅰ test were performed to evaluate dry eye signs and the association between dry eye symptoms and signs.The eyes were divided into corneal staining positive and negative group according to the presence or absence of corneal fluorescein staining, and the dry eye symptoms of the two groups were assessed by the three questionnaires.The eyes were divided into tear-deficient dry eye, evaporative dry eye, mixed dry eye and abnormal tear dynamics dry eye to compare the difference of dry eye signs among the groups.This study adhered to the Declaration of Helsinki.The study protocol complied with Chinese regulations and rules on clinical trial research and was approved by Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Putuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from patients before entering the cohort.Results:The total score of Chinese Dry Eye Questionnaire, OSDI questionnaire and DEQS questionnaire was 12.00(7.00, 16.00), 25.00(17.50, 36.93) and 32.02(15.77, 52.34), respectively.It was found that 130 eyes (92.2%) had dryness, and 109 eyes (77.3%) had ocular fatigue and 108 eyes (76.6%) had foreign body sensation.Dryness, foreign body sensation, photophobia and poor vision were weakly positively correlated with corneal staining ( r=0.177、0.297、0.172, all at P<0.05). Pain, photophobia and poor vision were negatively correlated with tear secretion ( r=-0.178, -0.197, -0.174; all at P<0.05). It was found that 43.3% of dry eye patients had used visual display terminals.Among the 141 eyes, 75 eyes (53.2%) were with over evaporation dry eye, 43 eyes (30.5%) with mixed dry eye, 18 eyes (12.8%) with aqueous-deficient dry eye and 3 eyes (2.1%) with abnormal tear dynamics dry eyes. Conclusions:Initial diagnosis of dry eye patients is mainly mild to moderate.Dry eye signs and symptoms are correlated.Over evaporation dry eye is the most common type of dry eye.The concordance between the Chinese dry eye diagnostic criteria and the Asian Dry Eye Society diagnostic criteria reaches 97.2%.

Objective:To investigate the expressions of MUC1, MUC4, MUC5AC and MUC16 in patients with first diagnosis of dry eye and their correlation with dry eye symptoms and signs.Methods:A cross-sectional study was conducted.Sixty-nine dry eye patients (69 eyes) as dry eye group and 40 normal volunteers (40 eyes) as normal control group were recruited in Xiamen Eye Center of Xiamen University, Beijing Tongren Hospital, West China Hospital of Sichuan University and Shanghai Puotuo District Center Hospital from December 2016 to May 2018.Symptoms were evaluated by Chinese dry eye questionnaire, Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality-of-Life Score Questionnaire (DEQS). Signs were assessed by tear film breakup time (TBUT), keratoconjunctival fluorescein sodium staining, and Schirmer I test.Conjunctival cells were collected by conjunctival impression cytology.The expression levels of MUC1, MUC4, MUC5AC and MUC16 mRNA in the two groups were determined by real-time fluorescence quantitative PCR.The correlation between the mRNA levels of conjunctival mucins and dry eye symptoms and signs were analyzed by Spearman correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Xiamen Eye Center of Xiamen University (No.2017003), Beijing Tongren Hospital, Capital Medical University (No.TREC2016-29), West China Hospital of Sichuan University (No.2016310) and Shanghai Puotuo District Center Hospital (No.PTEC-A-2016-18-1). Written informed consent was obtained from each subject before any medical examination.Results:The expression levels of MUC1 and MUC16 mRNA in dry eye patients were 3.277(0.568, 5.790) and 1.815(1.048, 3.694), which were higher than 1.055(0.550, 2.010) and 1.024(0.541, 1.965) in normal control group (Z=819.00, P=0.008; Z=861.00, P=0.002). According to OSDI scores, MUC1 was mainly increased to 3.277(1.161, 6.226) in mild to moderate (12-32 points) dry eye patients (Z=9.04, P=0.029), and MUC16 was mainly increased to 1.968(1.074, 3.726) in severe (>32 points) dry eye patients (Z=12.24, P=0.007). MUC1 expression was positively correlated with TBUT, and was negatively correlated with corneal staining scoring and keratoconjunctival staining scoring ( r s=0.270, P=0.025; r s=-0.331, P=0.006; r s=-0.325, P=0.007). MUC16 expression was positively correlated with TBUT, and was negatively correlated with blurred vision scoring, symptom exacerbation scoring during reading, impact scoring of driving at night, impact scoring of computer and impact scoring of TV use ( r s=0.249, P=0.039; r s=-0.359, P=0.047; r s=-0.370, P=0.034; r s=-0.558, P=0.016; r s=-0.498, P=0.006; rs=-0.515, P=0.002). Conclusions:The gene expressions of MUC1 and MUC16 are higher in conjunctiva of dry eye patients.MUC1 mRNA expression is related to patients' signs.MUC16 mRNA expression is related to the quality of life of patients.