Objective To explore the effect of androgen on learning and memory ability and neurons in hippocampal CA1 region in senescence accelerated mouse prone strain/8(SAMP8).Methods Thirty 7-month-old male SAMP8 were randomly divided into sham-operation control group,castrated group and androgen replacement therapy after castration group.The dose of testosterone undecanoate(TU) was 37.4mg/(kg?15d).The capability of learning and memory was observed 45 days later through the Morris water maze(MWM) test and the change of neurons in hippocampal CA1 region was detected and analyzed by HE staining,immunohistochemal method and computer pathological image analysis system.Results 1.In the MWM test,the escape latency of castrated group were significantly prolonged(P0.05).2.With HE staining,neurons in hippocampal CA1 region of castrated group were found with diffused vacuolar degeneration,and sparse and disordered cellular arranpement.The cell nucleuses were karyochrome and karyopycnosis.The number and optical density of A? immune positive neurons were markedly higher than those of other groups(P

Objective To investigate the effect of cocaine-amphetamine-regulated transcript peptide (CART) on the content of 4-hydroxy-2-noneral (HNE) and infarct volume after cerebral ischemia/reperfusion in mice.Methods A total of 96 healthy male mice were randomly divided into four groups:ischemia/reperfusion (n =27),CART (n =27),normal saline control (n =27) and sham operation (n =15) groups.A middle cerebral artery occlusion (MCAO) model was induced.Two hours after MCAO,CART 55-102 and equivalent normal saline were injected respectively via the tail veins of mice in the CART group and the normal saline control group,and then they were injected every other 24 hour.The neurological scores,infarct volume and the HNE content of lipid metabolism of oxidative stress were performed and detected respectively at 12,24,48 and 72hours after reperfusion.Results CART could significantly improve the neurological deficit scores (all P ＜0.05) and reduce infarct volume (all P＜0.05) at different time points after ischemia/reperfusion.The content of HNE was upregulated (all P＜0.05) at different points after referfusion.CART could significantly down-regulate the increased HNE levd in brain after ischemia (all P＜0.05).Conclusions CART may protect ischemic brain injury in mice by inhibiting lipid peroxidation.

Objective To assess the safety of early subcutaneous injection of a low-dose low molecular weight heparin (LMWH) nadroparin for prevention of deep vein thrombosis (DVT) in patients with spontaneous intracerebral hemorrhage (sICH).Methods The patients with sICH who early using nadroparin or lower limb intermittent pneumatic compression (IPC) for prevention of DVT were enrolled.A nadroparin group continuously injected nadroparin 0.4 ml/d subcutaneously for 10 days at day 4 after admission and an IPC group used lower limb IPC.Head CT was reexamined and hematoma volume changes were evaluated at day 3,5,and 14 after admission.The hemorrhagic events during the course of treatment were documented,and the lower limb DVT was examined by color Doppler sonography.Results A total of 94 patients with acute sICH (n =41 in the nadroparin group,n =53 in the IPC group) who early use of nadroparin or IPC for prevention of DVT were enrolled.Fourteen patients had lower limb DVT,5 (12.2％) of them were in the nadroparin group and 9 (17.0％) of them were in the IPC group.However,there was no significant difference in the incidence of DVT between the two groups (x2 =0.418; P =0.518).During the treatment,no patient experienced increased intracranial hematoma and rebleeding.Conclusion Early subcutaneous injection of low-dose nadroparin for the prevention of DVT in patients with sICH is safe.

Objective To investigate the effect of cocaine and amphetamine-regulated transcript (CART ) peptides on cortical synaptic plasticity in ischemia-reperfusion (I/R ) injury mice. Methods A total of 288 healthy male specific pathogen free(SPF)grade Kunming mice aged 0 to 12 weeks were selected. They were divided into four groups:I/R group (n =81 ),I/R +CART group (n =81),sham operation group (n=63),and sham operation+CART group (n=63)according to the random number table method. A model of middle cerebral artery occlusion (MCAO)for 2 h and reperfusion was induced. Before reperfusion,the mice of the I/R+CART group were injected CART via tail vein (0. 5μg, 200μl)and the those of the sham operation+CART group were injected equal CART;repeated administration once every 24 hours. 2,3,5-Triphenyl tetrazolium chloride assay was used to detect cerebral infarction volume of the I/R group and the I/R+CART group at different time points (24 h,72 h,and day 7 )after achieving reperfusion. The transmission electron microscope was used to observe the ultrastructural changes of synapses at different time points,and the synaptic morphological parameters were analyzed quantitatively. Western blot was used to observe the expression level of postsynaptic density 95 (PSD-95)proteins in the surrounding area of cortical infarct at 72 h after reperfusion. Results (1 )Compared with the sham operation group,the number of synapses was significantly decreased in the cortical slices in the I/R group (3. 37 ± 0. 38μm2 vs. 7. 04 ± 0. 55μm2 ,2. 89 ± 0. 22μm2 vs. 6. 89 ± 0. 04μm2 ,3. 25 ± 0. 18μm2 vs. 6. 78 ± 0. 42μm2;all P<0. 05). The density of PSD was significantly decreased (24. 4 ± 2. 8 nm vs. 47. 3 ± 6. 1 nm,23. 8 ± 3. 7 nm vs. 46. 5 ± 7. 5 nm,24. 6 ± 2. 2 nm vs. 48. 1 ± 5. 1 nm;all P <0. 05). The width of synaptic cleft was increased (25. 2 ± 2. 1 nm vs. 21. 5 ± 1. 6 nm,25. 2 ± 1. 4 nm vs. 21. 3 ± 1. 0 nm,23. 7 ± 2. 6 nm vs. 21. 6 ± 1. 6 nm;all P<0. 05). The expression level of PSD-95 protein was decreased at 72 h after reperfusion (P<0. 05). (2)Compared with the I/R group,the infarction volume of the I/R+CART group was significantly reduced at 24 h,72 h,and day 7 after reperfusion (29. 0 ± 1. 9% vs. 36. 3 ± 1. 4%,38. 1 ± 1. 4% vs. 47. 6 ± 2. 7%,and 36. 0 ± 2. 8% vs. 42. 5 ± 2. 0%,respectively;all P<0. 05). The number of synapses was significantly increased (4. 32 ± 0. 35 μm2 )and the expression level of PSD-95 protein was increased at 72 h after reperfusion (P<0. 05). The PSD density (33. 8 ± 3. 4,34. 2 ± 4. 6,38. 2 ± 4. 0 nm)was thickened at 24 h,72 h,and day 7 after reperfusion (all P <0. 05),and there were no significant differences in the width of synaptic cleft at each time point(allP>0.05).Conclusion CART can reduce cerebral infarct volume of I/R in mice and improve synaptic plasticity of cortical neurons in mice after ischemic injury.

To study the effect of Gegen Qinlian decoction and its major effective components on five hepatic microsomal CYP450 isozymes in rats. The in vitro hepatic microsomal incubation technique was used to co-culture Gegen Qinlian decoction and its major effective components together with each probe substrate. HPLC-MS/MS was used to establish the analytical method for metabolites of the five isoform probe substrates of CYP450 isozymes, detect the linearity among micoromal protein concentration, incubation time and metabolite formation amount. And HPLC-MS/MS was applied to determine the formation rate (V) of corresponding metabolites (acetaminophen, 4-OH-chlorzoxazone, dextrophan, 6-OH-chlorzoxazone and 6β-hydroxytestosterone) specific probe substrates of the five isoform probe substrates of CYP450 isozymes (phenacetin, polbutamide, dextromethorphan, chlorzoxazone, testosterone), in order to determine the activity of each isozyme. The result showed good linearity among acetaminophen, 4-OH-tolbutamide, dextrophan, 6-OH-chlorzoxazone and 6β-hydroxytestosterone, satisfactory precision, stability and average recovery, suggesting the method was feasible. The optimized in vitro microsomal incubation conditions conformed to the requirements in the guideline of drug-drug interaction. Gegen Qinlian decoction showed different degrees of inhibitor effect on 5 CYP450 isoforms (CYP1A2, CYP2C11, CYP2D2, CYP2E1, CYP3A1/2). Its major effective component berberine could inhibit each CYP450 isoform at high concentrations (except for CYP1A2, CYP3A1/2).
Animals ; Chromatography, High Pressure Liquid ; methods ; Cytochrome P-450 Enzyme Inhibitors ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Isoenzymes ; antagonists & inhibitors ; Liver ; enzymology ; Rats ; Tandem Mass Spectrometry ; methods

Objective Toinvestigatetheclinicalsignificanceofplasmamatrixmetalloproteinase9 (MMP-9)intheformationofdelayedcerebraledemaafterintracerebralhemorrhage.Methods The clinical data of 107 patients with spontaneous intracerebral hemorrhage treated with conservative medical treatment were analyzed retrospectively. According to the clinical features and imaging changes,they were divided into either a delayed cerebral edema group (case group n=39)or a non-delayed cerebral edema group (control group n =68 ). The plasma MMP-9 level was detected with enzyme-linked immunosorbent assay within 24 h after onset. The patients performed head CT scan again at day 7 and 14 after admission. The changes of hematoma and edema volume were detected. All the possible factors associated with the formation of delayed cerebral edema were firstly analyzed by the univariate analysis. Univariate analysis showed that the variables with significant differences were enrolled into multiple logistic regression analysis. Results TheplasmaMMP-9levelofthedelayedbrainedemagroupwassignificantlyhigherthanthatof the control group,they were 189 ± 51 and 118 ± 27 mg/L respectively (P<0. 01). The result of univariate analysis showed that age,history of smoking,blood glucose level,baseline hematoma volume,and National Institute of Health stroke scale (NIHSS )score on admission might be associated with the formation of delayed cerebral edema after intracerebral hemorrhage. Logistic regression analysis showed that MMP-9 level (OR,9. 745,95%CI 6. 754-15. 466,P<0. 01),baseline hematoma volume (OR,2. 411,95%CI 1. 190-2. 728,P =0. 018),blood glucose level on admission (OR,1. 327,95%CI 1. 133 -1. 850,P =0.004),and NIHSS score (OR,1. 867,95%CI 1. 272-2. 364,P=0. 020)were the independent risk factorsfortheformationofdelayedcerebraledemaafterintracerebralhemorrhage.Conclusion Theamount of bleeding,NIHSS score,and hyperglycemia are the risk factors for the formation of delayed cerebral edema in patients with spontaneous intracerebral hemorrhage,while high MMP-9 level on admission indicated that the risk of the formation of delayed cerebral edema is high.

Objective:To investigate the predictive value of matrix metalloproteinase-9 (MMP-9) and neutrophil to lymphocyte ratio (NLR) in delayed perihematomal edema (dPHE) after spontaneous intracerebral hemorrhage (sICH).Methods:Patients with sICH admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School within 24 h of onset from January 2018 to June 2020 were enrolled retrospectively. Serum MMP-9 levels and peripheral blood cell counts were detected, and NLR were calculated within 24 h of onset. dPHE was defined as an increase of 3 ml in absolute edema volume at 10-21 d after onset of sICH compared with that at 5-9 d. The demographic and baseline clinical and imaging data of the dPHE group and the non-dPHE group were compared. Multivariate logistic regression analysis was used to identify the independent predictors of dPHE. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values of MMP-9 and NLR for dPHE. Results:A total of 195 patients with sICH (61.88±10.60 years old) were enrolled in the study. One hundred and forty-eight patients were males (75.9%). There were 53 patients (27.2%) in the dPHE group and 142 (72.8%) in the non-dPHE group. Univariate analysis showed that age, baseline hematoma volume, baseline National Institutes of Health Stroke Scale score, fasting blood glucose, high-sensitivity C-reactive protein, MMP-9, neutrophil count, NLR and the proportion of irregular hematoma in the dPHE group were significantly higher than those in the non-dPHE group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, higher MMP-9 (odds ratio [ OR] 4.291, 95% confidence interval [ CI] 2.041-6.590; P=0.007) and higher NLR ( OR 2.530, 95% CI 1.157-4.022; P=0.011) were all the independent predictors of dPHE. ROC curve analysis showed that the area under the curve of MMP-9 for predicting dPHE was 0.819 (95% CI 0.756-0.884; P<0.001), the optimal cut-off value was 164.0 μg/L, and the sensitivity and specificity were 86.79% and 66.90% respectively. The area under the curve of NLR for predicting dPHE was 0.788 (95% CI 0.719-0.856; P<0.001), the optimal cut-off value was 5.683, and the corresponding sensitivity and specificity were 77.36% and 71.13% respectively. Conclusions:sICH patients with higher baseline MMP-9 and NLR are more likely to develop dPHE. Early detection of MMP-9 and NLR in peripheral blood after admission can predict dPHE.

Objective To explore the relationship between folic acid levels of cord blood and birth weight, hyaline membrane disease in newborns. Methods Eighty-seven newborns were divided into premature infant group(42 cases) and term infant group(45 cases),intrauterine growth retardation group( 28cases) and control group (59 cases), hyaline membrane disease of premature infant group ( 13 cases) and premature infant control group(15 cases) according to the gestational age, birth weight, clinical manifestation and chest X-ray, respectively. Folic acid levels of cord blood were measured. Results The folic acid level of cord blood in premature infant group was lower than that in term infant group [(10.87 ±4.31) nmol/L vs.( 13.56 ± 5.07) nmol/L,P ＜0.05 ]. The folic acid level of cord blood in intrauterine growth retardation group was lower than that in control group [(11.01±4.29)nmol/L vs.( 14.87 ± 5.14)nmol/L,P＜0.05]. The folic acid level of cord blood in hyaline membrane disease of premature infant group was lower than that in premature infant control group [(9.15 ±4.02) nmol/L vs.(12.91±4.51) nmol/L,P＜0.05]. The positively correlation was found between the folic acid level of cord blood and birth weight in newborns (r =0.1825).Conclusion The folic acid level of cord blood is correlated with the occurrence of premature infants,intrauterine growth retardation and hyaline membrane disease in newborns.

Objective: To explore the risk factors of bronchial asthma in children with allergic rhinitis, and to provide evidence for the early diagnosis, treatment and prevention of asthma in children with allergic rhinitis. Methods: Children with allergic rhinitis and children with allergic rhinitis and asthma, who attended the Allergy Clinic of the Capital Institute of Pediatrics from November 2019 to October 2020, were recruited for the study. Medical history, clinical characteristics, allergen types and risk factors were collected and analyzed. Results: A total of 117 children with allergic rhinitis and 111 children with allergic rhinitis that subsequently developed into asthma were included. The results of the univariate analysis showed that the occurrence of asthma in children with allergic rhinitis was associated with the course of rhinitis, severity of rhinitis, type of rhinitis, seasonal onset, history of pet contact, family history of allergic diseases, mold, ragweed, dermatophagoides culinae and dust mite sensitization( χ 2=6.15, 8.79, 3.99, 9.44, 5.17, 4.43, 8.48, 10.38, 6.18, 5.31, P <0.05). The Logistic regression analysis showed that rhinitis severity( OR = 7.03 ), family history of allergic diseases( OR =8.24), mold( OR =5.19), and household dust mite sensitization ( OR =25.25) were positively correlated with the occurrence of asthma in children with allergic rhinitis( P <0.05), and dust mite sensitization was the strongest risk factor. Conclusion The development of asthma in children with allergic rhinitis is affected by many factors, among which the severity of rhinitis, family history of allergic diseases and dust mite sensitization are the most important factors.

Objective To investigate the effects of mercury on T lymphocytes and serum immune indexes of workers with Methods occupational mercury exposure. A total of 45 workers with occupational mercury exposure were selected as the ， mercury exposure group and 47 workers without occupational mercury exposure were selected as the control group using the judgment sampling method. Cold atomic absorption spectrometry was used to detect the urinary mercury level of the two groups. （ ） +， + +， + + - + Flow cytometry was used to detect the proportion of cluster of differentiation CD 3 CD3CD4 CD3CD8 and CD3CD19 ， - （ - ） - （ - ） cells in peripheral blood and the levels of tumor necrosis factor α TNF α and interleukin 8 IL 8 in serum. The levels of （ ） ， Results immunoglobulin Ig A IgG and IgM in serum were measured by immune nephelometry. The urinary mercury level of （ ： vs ，P ） individuals in the mercury exposed group was higher than that of the control group median 92.7 13.2 μg/g Cr <0.01 . The +， + +， - + proportion of CD3 CD3CD4 CD3CD19 cells in peripheral blood and serum IgG level in the mercury exposed group （ P ）， - - （ P ） decreased all <0.05 and the serum TNF α and IL 8 levels increased all <0.01 compared with the control group. Urinary - + mercury level was negatively correlated with the proportion of CD3CD19 cells in peripheral blood and serum IgG level in the ［ （r） ， ， P ］， study subjects Spearman correlation coefficient S were −0.21 and −0.31 respectively all <0.05 and positively - - （r ， ， P ） ， correlated with serum TNF α and IL 8 levels S were 0.36 and 0.39 respectively all <0.05 . However the urinary mercury （ P ）， +， + +， level was neither correlated with IgA and IgM levels in serum all >0.05 nor with the proportion of CD3 CD3CD4 + + （ P ） Conclusion CD3CD8 cells in peripheral blood all >0.05 . Occupational exposure to mercury can lead to abnormal ， changes in peripheral blood T lymphocyte subsets B lymphocytes and serum immune factors in workers. The mercury load of occupational mercury exposure workers may impact their immune function.