This article reviews the proteins and transduction pat hw ay in endotoxic action. Lipopolysaccharide-binding protein(LBP) binds and trans ports the LPS to its receptors, which include CD14 and CD11/CD18. Toll-like rec eptors(TLRs) is closely associated with transducting the signals into cytoplasm. Scavenger receptors are related to hepatic clearance on endotoxin .The intracel lular signal transduction is involved in several paths which finally leads to t he release of cytokines.

To study the effects of forkhead transcription factor O1 (FoxO1) on the expression of type Ⅳ collagen and desmin in podocytes of diabetic rats.Streptozotocin-induced diabetic rats were divided into three groups:diabetic rats (DM group),rats transfected with blank lentiviral vectors (diabetes mellitus plus LV-pSC-GFP group,LV-NC group),and rats which were transfected with lentiviral vectors carrying constitutively active FoxO1 (diabetes mellitus plus LV-FoxO1-AAA group,LV-CA group).Rats which received an injection of diluent buffer served as normal control.At 2,4,and 8 weeks after transfection,the levels of urine albumin,blood glucose,blood urea nitrogen,and serum creatinine were measured.Realtime PCR and Western blotting were performed to measure the mRNA and protein levels of FoxO1,COL4A3,COL4A5,and desmin in the renal cortex.Moreover,light microscope and electron microscope were used to observe the structural changes in glomerulus and podocytes.Compared with LV-NC and DM group,in LV-CA group,there was a significant increase in the mRNA and protein levels of FoxO1,and a distinct decrease in the levels of urine albumin,blood urea nitrogen and serum creatinine of rats (except at the twoweek time point) (all P＜0.05),the mRNA and protein levels of COL4A3,COL4A5,and desmin were all decreased (all P＜0.05),and pathological changes in kidney were also improved.Upregulating the expression of FoxO1 by transfecting with constructed lentiviral vectors can definitely improve the abnormal expression of type Ⅳ collagen and desmin in podocytes of diabetic rats.

Objective To study the effect of 1,25-dihydroxyvitamin D3 on bone metabolism in diabetic rats and the related molecular mechanism.Methods A total of 45 healthy 6-8 weeks old male Sprague Dawley (SD) rats were treated with streptozotocin.The streptozotocin-induced diabetic rats were randomly assigned to diabetic group (DM),low dose vitamin D treated group(LD),and high dose vitamin D treated group(HD).Another 12 healthy SD rats were used as normol control group(NC).The rats in NC group and DM group were fed with 0.05 ml/d nut oil;those in the LD group and HD group were fed respectively with 0.03 and0.10 μg · kg-1 · d-1 1,25-dihydroxyvitamin D3 dissolved in 0.05 ml nut oil.12 weeks later,serum calcium,phosphorus,osteocalcin,type Ⅰ collagen cross-linked telopeptide (NTX),and 24 h urinary calcium were determined.Right femurs were harvested for pathohistological analysis by hematoxylin-eosin (HE) staining.Expressions of osteoprotegerin,receptor activator nuclear factor κB ligand (RANKL),core binding factor α1(Cbfa1) were detected by immunohistochemical staining.The osteoprotegerin,RANKL,Cbfa1,osteocalcin mRNA levels of bone tissue were performed by realtime quantitative reverse transcription polymerase chain reaction assay.Results (1) Compared with the NC group,serum calcium and 24 h urinary calcium in LD and HD groups were significantly higher (P＜0.05) ; 24 h urinary calcium in DM group was significantly higher than that in NC group (P ＜ 0.05).(2) Serum osteocalcin level in DM and LD groups was significantly lower than that in NC group (P＜0.05) ; there was no significant difference between the serum NTX levels of all groups (P＞0.05).(3) There was no significant difference in the mRNA expression of Cbfa1 in all groups (P＞0.05).The mRNA expression of osteocalcin in DM group was significantly lower than that in NC group (P ＜0.05).The mRNA expression of RANKL in DM group was significantly lower than that in NC group (P＜0.05) ; and that in LD and HD group was significantly higher than that in DM group (P＜0.05),and that in HD group was significantly higher than that in LD group (P＜0.05).The mRNA expression of osteoprotegerin in DM group was significantly lower than that in NC group (P＜0.05).The ratio of RANKL to osteoprotegerin in HD group was significantly higher than that in DM group (P＜0.05).Conclusions Vitamin D may promote bone metabolism in diabetic rats by up-regulating the expressions of osteocalcin and RANKL or in addition to other means.

Objective To clarify the clinical features and genetic background of a kindred of primary pigmented nodular adrenocortical disease (PPNAD).Methods Detailed clinical characteristics and laboratory test results from a ten-year old girl diagnosed as PPNAD were collected.Seven members of her family were screened for Cushing syndrome and Carney complex,and their blood DNA was extracted and sequenced for PRKAR1A,PDE11A,PDE8B and CTNNB1 mutations with ABI3730.Results The girl presented with symptoms and signs of hypercortisolism,while no features of Carney complex were observed.Hypercortisolemia,suppressed corticotrophin and high urinary free cortisol level were revealed.Cortisol level could not be suppressed both in high and low dose dexamethasone suppression test.The diagnosis of adrenocorticotrophic hormone (ACTH)-independent Cushing syndrome was established.Image and pathology of adrenal glands were in accordance with PPNAD.Other family members showed no evidence of Cushing syndrome or Carney complex.DNA sequencing showed that the patient harbored a missense mutation,C18G.Her father and younger sister were proved to be carriers of this mutation.Conclusion A Chinese PPNAD family was identified clinically and genetically,and a novel missense mutation of PRKAR1A was found.

Objective To evaluate the diagnostic value of triptorelin stimulation test in disorders due to delayed puberty.Methods Triptorelin stimulation test was carried out in 128 teenagers with delayed puberty,due to idiopathic hypogonadotropic hypogonadism(IHH) in 77 cases and constitutional delayed puberty(CDP) in 51.Blood samples were obtained 15 min before and 0,30,60,and 120 min after tripotorelin administration,and the levels of LH and FSH were determined.An extended GnRH stimulation test was carried out in 3 patients with IHH.Results Peak LH,peak FSH,and LH increment were parameters with high diagnostic value.A cut-off point at 8.2 IU/L of peak LH showed a sensitivity of 87％ and a specificity of 80.4％ in the differential diagnosis of IHH and CDP.Conclusion Peak LH cut-off point at 8.2 IU/L of triptorelin stimulation test seems to be sufficient to confirm diagnosis of IHH and CDP.An extended GnRH stimulation test may distinguish hypothalamic from the pituitary hypogonadotropic hypogonadism.

Objective To study the effect and mechanism of forkhead transcriptionfactor O1( FoxO1) on proliferation of rat mesangial cells(MCs) cultured under high glucose conditions. Methods Constructing lentiviral vectors of LV-CA-FoxO1 and LV-siRNA-FoxO1 were used to upregulate or downregulate FoxO1. Moreover, negative control LV-NC-FoxO1 was also constructed. Rat MCs were separately cultured in normal glucose(5. 6 mmol/ L, NG group), only high glucose(30 mmol/ L, HG0 group), LV-NC-FoxO1 with HG(HG1 group),LV-CA-FoxO1 with HG (HG2 group), and LV-siRNA-FoxO1 with HG(HG3 group) for 72 h. MTT assay and flow cytometrywas were used to analyze cell proliferation and cell cycle distribution. The expression of FoxO1, cyclin-dependent kinase inhibitor (p27), cyclinD1, and cyclin-dependent kinase 4( CDK4) were detected by QRT-PCR and Western blot. Results The MCs proliferation rate in HG0 group was faster than that in NG group. Besides, there were no statistical differences in FoxO1 expression and proliferation rate of MCs between HG0 group and HG1 group. Nevertheless, LV-CA-FoxO1 promoted cell cycle arrest at the G1 phase and attenuated proliferation rate, along with upregulation of FoxO1 and p27 and downregulation of cyclin D1 and CDK4 in HG2 group ( all P < 0. 05). Moreover, degradation of FoxO1 by LV-siRNA-FoxO1 stimulated hyperproliferation of MCs, associating with decline of p27 and increase of cyclin D1 and CDK4 in HG3 group(all P<0. 05). Conclusion The proliferation of MCs induced by high glucose is regulated by utilizing transgenic technology targeted and regulated FoxO1 expression and consequently through FoxO1 / p27 signaling pathway. These findings indicate that FoxO1 seems to be a new therapeutic target for early diabetic nephropathy.

Objective To study the role and molecular mechanism of forkhead transcription factor O1 (FoxO1) on proliferation of mesangial cells( MCs) in diabetic rats. Methods Empty lentiviral vector( LV-pSC-GFP) and the constitutively active FoxO1 lentiviral vector(LV-CA-FoxO1) were constructed. Diabetic rat model was established and rats were divided into diabetes group(DM group), diabetes with LV-pSC-GFP group(NC group), and diabetes with LV-CA-FoxO1 group(CA group). The normal SD rats of the same age were considered as the normal control group(NG group). The lentiviral vector was injected into the renal cortex of diabetic rats in corresponding groups. Body weight, blood glucose, 24 h urinary protein, urine albumin, serum creatinine, and blood urea nitrogen was detected at the end of 2 weeks, 4 weeks, and 8 weeks. The ratio of kidney weight/ body weight was counted and the renal cortex was reserved for light microscopy, electron microscopy and frozen section after rats were sacrificed in different groups. The mRNA level of FoxO1 and p27Kip1 were detected by real-time PCR. The protein expressions of FoxO1, p-FoxO1, and p27Kip1 were tested by Western blotting. Results The renal pathological changes were obviously ameliorated in CA group. Compared with DM group, the mRNA and protein expression of FoxO1 and p27Kip1 were significantly increased in CA group (P<0. 05), whereas there was no difference in the expression of p-FoxO1 protein(P > 0. 05). The p-FoxO1 / FoxO1 ratio was decreased ( P < 0. 05). All indexes had not reached statistical difference between NC group and DM group(P>0. 05). Conclusion Overexpression of FoxO1 in kidneys of diabetic rats can inhibit the proliferation of mesangial cells, and may through up-regulating the expression of p27Kip1 delay the progression of diabetic nephropathy.

Objective? To investigate the effect of intervention theory based on timing theory on self-management behavior and medication compliance of patients with percutaneous coronary intervention (PCI). Methods? A total of 126 patients who underwent PCI in People＇s Hospital of He＇nan Province in 2018 were enrolled, including 67 who had PCI from April to June in 2018 in the experimental group and 59 who had PCI from January to March in 2018 in the control group. Patients in the control group received routine nursing intervention. The patients in the experimental group were treated with an intervention program based on timing theory. The Coronary Heart Disease Self-Management Scale and the Morisky Medication Adherence Questionnaire were used to compare the effects of the intervention. Results? After intervention, the scores of "daily life management(17.11±3.62)", "bad habit management(16.33±4.36)", "disease knowledge management(17.11±3.68)", "symptom management(14.25±4.15)", "first aid management(13.55±4.27)","treatment compliance management(11.13±3.62)" and "emotional cognitive management(15.69±4.25)" in the experimental group were higher than the control group with(14.57±3.69),(14.17±3.88),(14.36±3.56), (12.34±4.46),(10.41±3.89),(7.69±4.14),(13.23±4.32)respectively, and the differences were statistically significant (t=3.895, 2.921, 4.250, 2.489, 4.293, 4.976,3.217;P＜0.05). After the intervention, the scores of the medication adherence questionnaire in the experimental group was (6.35±1.12), and the control group was (5.92±1.17). The difference between the two groups was statistically significant (t=2.106, P=0.037). Conclusions? Timing theory can improve the self-management behavior and medication compliance of PCI patients, and can be applied in clinical practice.

Objective:To explore the risk factors of venous leg ulcers (VLU) in patients with deep venous thrombosis (DVT) of central type.Methods:Using the convenient sampling, 268 patients with lower limb DVT of central type who were treated in the Vascular Surgery of Henan Provincial People's Hospital from January 2020 to January 2021 were selected for analysis. Patients were divided into a case group ( n=56) and a control group ( n=212) based on whether VLU occurred. Clinical factors were compared between the two groups. The risk factors for VLU in patients with lower limb DVT of central type were determined using univariate analysis and multivariate Logistic regression. A prediction model was constructed. The performance of the prediction model was evaluated using the Hosmer-Lemeshow test of goodness of fit and the area under the receiver operating characteristic (ROC) curve. Results:Univariate analysis showed that there were statistical differences between the two groups in terms of age, body mass index, smoking, alcohol consumption, work style, hypertension, deep venous reflux of the lower limbs, history of lower limb DVT, fracture history, Morisky Medication Adherence Scale scores, post-thrombotic syndrome, family history of lower limb varicose veins and family history of lower limb DVT ( P<0.05) . Multivariate Logistic regression analysis showed that age>60 years old, smoking cigarettes every day, post-thrombotic syndrome, hypertension and deep venous reflux were independent risk factors for VLU in patients with lower limb DVT ( P<0.05) . The area under the ROC curve of the risk prediction model for VLU in patients with lower limb DVT of central type was 0.972 (95% confidence interval was 0.945 to 0.988) . Conclusions:Age>60 years old, smoking cigarettes every day, post-thrombotic syndrome, hypertension, and deep venous reflux are independent risk factors for VLU in patients with lower limb DVT of central type. Nurses should provide prevention and treatment measures for the risk factors of VLU in patients with lower limb DVT of central type so as to reduce the incidence of VLU.