Inverse agonist is a new type of drug acting on receptors.Its research has experienced several stages, including discovery of ethylβ-carboline 3-carboxylate,activity study,proposal of the concept,two-state model,and constitutive activity theory in succession.Most G protein-coupled receptors possess constitutive activity,i.e.a proportion of receptors are in active state and can produce effects without any agonist.Inverse agonist has an affinity to receptors,but no intrinsic activity,so it cannot activate receptors.However,it can antagonize the constitutive activity of receptors,and produce an opposite effect on the corresponding agonist.Both agonist and inverse agonist can produce their effect alone with different mechanisms.Agonist activates its receptors,but inverse agonist antagonizes them.Both inverse agonist and antagonist can antagonize receptors.However,inverse agonist and antagonist antagonize the constitutive activity of receptor and the agonist’s effects,respectively.Inverse agonists can be used to treat diseases with enhanced constitutive activity,up-regulate and sensitize receptors with constitutive activity.Moreover,endogenous inverse agonists can maintain a specific physiological function.The study on inverse agonist has a theoretical significance in perfecting receptor theory as well as a clinical value in diagnosis and treatment of diseases with enhanced constitutive activity.

A model of s bacute senility state was established in mice by successive retrobulbar injectiou of 80 mg/kg D-galactose for 50 days. Concomitant oral administration of 4 g/kg and 8 g/kg gastrodia can effectively recovcr the decreased ability of the passive avoid ance reaction in the model animals.The activity of RBC SOD and the contents of hydroxyproline in the animals skin were markedly increased as well as the lipofuscin of myocardium. However, gastrodia was less effective to lower lipofuscin in liver and brain.

Objective To explore the diagnostic value of quantitative test of 14-3-3 protein content in cerebrospinal fluid(CSF)in sporadic Creutzfeldt-Jakob disease(sCJD).Methods The Capture Assay was used to detect the level of CSF 14-3-3 protein in 14 cases of sCJD(sCJD group),10 cases of other dementia(OD group),12 cases of non dementia(ND group).Results The media of 14-3-3 protein content was 40.00 ng/mg in sCJD group,2.65 ng/mg in OD group,and 3.10 ng/mg in ND group,respectively.It was significantly higher in sCJD group than that in groups OD and ND(all P

24 ng/ml,sensitivity and specificity were 90% and 92.9% respectively.Conclusions The diagnosis value of 14-3-3 protein in CSF is higher than that of NSE. The combination of CSF 14-3-3 protein and NSE can improve the sensitivity and specificity in diagnosis of CJD.

Objective To investigate the predictive values of hypoxia-induced factor(HIF)- 1α and vascular endothelial growth factor (VEGF) in patients with type 2 diabetic kidney disease, and its relationship between HIF-1α, VEGF and glomerular filtration rate (eGFR). Methods Seventy-six patients with type 2 diabetic kidney disease were divided into two groups:DKD1 group [eGFR>90 mL/(min·1.73 m2),n=48] and DKD2 group [60 mL/(min·1.73 m2)0.05). Serum levels of HIF-1α and VEGF were significantly higher in DKD2 group than those of DKD1 group (P<0.05). There were negative correlation between VEGF and HIF-1αlevels with eGFR level (r=-0.59, P<0.01;r=-0.55, P<0.01). ROC curve showed that serum VEGF and HIF-1αlevels were above the opportunity diagonal. The diagnostic sensitivities of HIF-1 to DKD1 and DKD2 were 92.1%and 87.4%. The diagnostic specificities of HIF-1 to DKD1 and DKD2 were 91.7%and 85.4%. The diagnostic sensitivities of VEGF to DKD1 and DKD2 were 96.1%and 86.2%, and specificities were 93.3%and 89.1%. Conclusion Serum levels of VEGF and HIF-1αchange with the severity of diabetic nephropathy are likely to be an early predictor for the progression of diabetic kidney disease.

Objective_ To investigate the effect of resting heart rate on the progression to diabetes in impaired glucose regulation patients. Methods A total of 638 patients with impaired glucose regulation, from January 2011 to December 2012 in our endocrinology clinic, were selected for the study. According to the resting heart rate, patients were divided into four groups:<66 beat/min group, 66 to 69 beat/min group, 70 to 75 beat/min group, and>75 beat/min groups. All patients'baseline data were collected. The incidences of diabetes in different resting heart rate groups were compared, and the relationship between resting heart rate and the progression to diabetes was estimated using multiple regression analysis. Results In 704 patients with impaired glucose regulation, 636 patients have been completed 2 years follow-up, or reached the end of follow-up ( diagnosed as diabetes ) , the follow-up rate was 90. 34%. During two years follow-up, the incidence of diabetes of<66 beat/min group, 66 to 69 beat/min group, 70 to 75 beat/min group, and>75 beat/min group were 16. 2%, 19. 4%, 25. 0%, and 33. 0%, respectivlely. And the Cochran Armitage trend test showed that χ2 =11. 109, P=0. 001, the difference was statistically significant ( P<0. 05). According to blood glucose monitoring, the 636 patients with impaired glucose regulation were divided into impaired fasting glucose group, impaired glucose tolerance group and impaired fasting glucose combined with impaired glucose tolerance group:the Cochran Armitage trend test showed that, with the resting heart rate accelerating, the incidence of diabetes increased. The incidence of diabetes in impaired fasting glucose combined with impaired glucose tolerance group was higher than that of impaired fasting glucose group and impaired glucose tolerance group ( P=0. 062, 0. 113). The average resting heart rate in 68 impaired glucose regulation patients progressed to diabetes was (79.8±8.3)beat/min,andin568non-diabetescases,itwas(74.5±7.2)beat/min(t=-5.043,P<0.01). With the use of patients progressing to diabetes as the dependent variable, different resting heart rate group as independent variables, and resting heart rate<66 beat/min group as a reference, the logistic regression analysis showed that the risk of the progression to diabetes increased with the resting heart rate levels. Conclusion Higher resting heart rate is linked to higher risk of diabetes in patients with impaired glucose regulation.

Objective To investigate the clinical effect of uterine artery embolization chemotherapy in the treatment of special site pregnancy .Methods 36 patients with special site pregnacy were randomly divided into the observation group and control group .The control group received uterine curettage after uterine artery embolization treatment,the observation group received bilateral uterine artery perfusion of methotrexate combined with uterine cu -rettage after embolization therapy .Time of-HCG returned to normal ,intraoperative blood loss ,hospitalization time and incidence rate of complications were compared between the two groups .Results After treatment,the time of -HCG returned to normal,intraoperative blood loss and hospitalization time in the observation group were (27.3 ±3.2)h, (120.5 ±18.3) mL,(85.6 ±8.4) h,which were significantly less than (76.4 ±8.2) h,(375.1 ±68.4) ml and (147.1 ±10.5)h in the control group (t=6.75,4.54,4.43,all P<0.05).The incidence rate of complication in the observation group was 16.8%,which was significantly lower than 50.1% in the control group (χ2 =4.49,P <0.05).Conclusion The uterine artery chemotherapy and embolization in the treatment of special parts of pregnancy can significantly shorten the hospitalization time and time of -HCG returned to normal ,reduce the intraoperative blood loss,the clinical effect is good ,it can be used as an effective method for the treatment of special site pregnancy .

Objective To evaluate the outcomes of distal leg and foot-ankle reconstruction with rotated single pedicel reverse sural neurocutaneous island flaps. Methods From June 2011 to January 2016, seventeen distal leg and foot-ankle defects cases repaired with rotated single pedicel reverse sural neurocutaneous island flap were analyzed retrospectively. In this study, 13 cases were male, and 4 cases were female. Age ranged from 25 to 65 years old, with an average age of 42.0 ± 8.3 years. Seven cases were distal leg defects, 3 cases were ankle defects, 3 cases were heel defects, and 4 cases were acrotarsium defects; all cases had bone and tendon exposure. The defects ranged from 5.0 cm × 7.0 cm-6.0 cm × 12.0 cm. The flap size ranged from 5.0 cm × 7.0 cm-8.0 cm × 15.0 cm. Results All 17 cases survived completely, without thanatosis, blisters and vascular crisis. The follow-up period was 12-48 months, and the mean was (20.0 ± 11.1) months. The color and elasticity of the flaps was excellent, with satisfactory appearances. Function and appearance of donor sites was not affected. Conclusions The rotated single pedicel reverse sural neurocutaneous island flaps have no injury on main nerves and arteries. The flaps have wide rotation angle and less invalid fold in the pedicel. The simple operation has satisfactory effects and high survival rate. It is a relatively easy procedure that can be applied toward repairing of distal leg and foot-ankle soft tissue defect.

Objective: To investigate the household eye hygiene among students at grades 3 to 5 in primary schools in Jinshan District, Shanghai Municipality, so as to provide insights into the management of myopia among children and adolescents. Methods: Students at grades 3 to 5 in primary schools were sampled in Jinshan District using a stratified cluster sampling method from December 2021 to January 2022. The household reading environments were observed, including the height of the learning desk and chair, desk surface color and strength. The duration of reading and writing, duration of watching TV and videos, duration of outdoor activities, duration of sleep and eye use behaviors and habits after school and at weekends were investigated using questionnaires. Results: A total of 330 primary school students were surveyed, including 179 boys (54.24%) and 151 girls (45.76%), and there were 36.36% grade 3 primary school students, 36.36% grade 4 students and 27.27% grade 5 students. There were 94.24% of primary school students that used the desk and chair with heights mismatched to students' heights, 25.45% that used desks with dark surface, 26.67% that used desks with light reflection, and 48.48% that used desk lamps with an illumination intensity of <300 lx. There were 56.36% of students with reading and writing duration of 1 h and longer, 15.76% with watching duration of 0.5 h and longer, 86.97% with outdoor activity duration of <1 h and 88.48% with sleep duration of <10 h after school, and 42.42% with reading and writing duration of 2 h and longer, 29.70% with watching duration of 1 hour and longer, 65.45% with outdoor activity duration of <2 h and 55.76% with sleep duration of <10 h at weekends. There were 30.91% of primary school students with 10 cm distance from chest to desk, 26.36% with 33 cm distance from eyes to books and 35.15% with 3 cm distance from fingers to pen points when reading and writing, and 35.45% with >3 m distance from TV, 40.91% with >50 cm distance from computers, and 22.73% with >40 cm distance from cell phones when watching TV or videos. Conclusions The household eye use environments remain to be improved, and there are poor eye use behaviors among primary school students at grades 3 to 5 in Jinshan District, Shanghai Municipality; notably, mismatch between the desk and chair height and students' body height and inadequate sleep are common.

Objective To investigate the dynamic changes and prognosis of thyroid function in the patients with chronic hepatitis C (CHC)after antiviral treatment,and to clarify the influence of baseline factors in the changes of thyroid function.Methods 243 CHC patients with normal baseline thyroid function were enrolled. All patients were treated with IFN-alpha-2b(IFN-α2b)combined with ribavirin for 48 weeks.The thyroid function and serum HCV RNA level were assessed at 12,24,36,48,60 and 72 weeks.According to the changes in thyroid function after treatment,the patients were divided into continued normal,subclinical hypothyroidism,hypothyroidism and hyperthyroidism groups.The regularity of the changes of thyroid function of the patients in various groups were observed.Results Among 243 CHC patients,82(33.7%)patients had thyroid dysfunction.The prevalence of subclinical hypothyroidism,hypothyroidism and hyperthyroidism were 20.9%(51/243),5.3%(13/243)and 7.4%(18/243),respectively. At the end of 72 weeks,there were 32 (39.0%)patients suffering from subclinical hypothyroidism,12 (14.6%) patients with hypothyroidism and 7 (8.5%) patients with hyperthyroidism rehabilitated.6(7.3%)patients suffering from hypothyroidism turned to subclinical hypothyroidism,and 3(3.7%) patients suffering from hyperthyroidism turned to subclinical hypothyroidism.19(23.2%)patients had no significant change,they performed for continued subclinical hypothyroidism (1,1.2%),hypothyroidism (13,15.9%)and hyperthyroidism (5 , 6.1%).In addition, 3 (3.7%)patients with hyperthyroidism turned to hypothyroidism.An increased risk for hypothyroidism was found in female patients compared with males (P<0.05);the average age of the patients with hyperthyroidism was lower than those of the patients with hypothyroidism, subclinical hypothyroidism and continued normal (P<0.05);the baseline levels of GGT in the patients with hyperthyroidism and hypothyroidism were lower than those of the patients with subclinical hypothyroidism and continued normal(P<0.05).The ratio of the patients with HCV 2a to the patients with hypertyroidism was higher than those of the patients with hypothyroidism,subclinical hypothyroidism and continued normal(P<0.05).Conclusion Thyroid function in the CHC patients can be affected by antiviral treatment. Gender, age, liver function, genotype of HCV are influencing factors for the changes of thyroid function.