Objective:To investigate the changes in plasma ET-1 and ANF in IDDM and its microvascular complication.Methods:The plasma levels of ET-1 and ANF were measured by radioimmunoassy in 31 patients with IDDM and 25 normal controls.Results:The plasma levels of ET-1 and ANF significantly increased in IDDM compared with the normal controls (P<0.01);and the levels were also markedly higher in diabetics with microangiopathy complications than in those withou the complications (P<0.01).The more kinds of microangiopathey complications,the higher level of the plasma ET-1 and ANF,which suggests that the elevation of plasma ET-1 and ANF may be concerned with the microangiopathy and ET-1 may reflect the degree of vascular endothelial cell damage.There were no significant correlation between plasma ET-1 or ANF and blood glucose,fructosamine and C-peptide,but the plasma levels of ET-1 and ANF both correlated with the duration of diabetes mellitus.And the plasma level of ET-1 positively correlated with ANF1 (P<0.01).Conclusion:The results of study suggest that ET-1 and ANF are both associated with the development,progress and severity of microvascular complications.

Objective To explore the role and possible mechanism of CD28/B7 molecules in T cell ab-normal activation by establishing a mouse model of the autoimmune aplastic anemia. Methods Unmanipulated B6D2F1 or CByB6F1 hybrid mice were infused with about 40 × 106 lymph node (LN) cells from their C57BL/6 (B6) parent. Distribution of the injected T cells was assayed by CFDA-SE fluorescent staining. Anti-D80 and anti-CD86 monoclonal antibodies were used to block CD28/B7 signal transduction pathways and to test the change of peripheral blood of F1 mice at different times. Damage was assessed by histological staining. Bone marrow (BM) cells and LN iymphocytes were cultured to observe the effect of different number of lymphocytes in the LN on BM cells' hematopoiesis by the count of hematopoietic colony-forming cells, and to test the effect of cyclosporine A of different concentration on BM cells' hematopoiesis. Results Infusion of about 40 × 106/mouse B6 LN cells led to the development of BM failure in the fifth day: anemia, neutropenia and thrombocytopenia. At 21st day recipients began to appear death. Frozen section revealed the injected lymph node major in myeloid tissue. Pathological sec-tion revealed obvious immune-induced marrow destruction and tissue destruction. There was similar performance of the above in the recipients infused with anti-D80 and anti-CD86 monoclonal antibodies. B6 LN five times the num-ber of lymphocytes in the blood cells F1, CFU-E and CFU-G colony formation of a blank group difference was not significant (P >0.05); When B6 LN 10 times the number of lymphocytes in the blood cells F1, CFU-E colony forming significantly reduce the number of (P < 0.05) ; When B6 LN lymphocytes 50 times in F1 hematopoietic cells, not observed CFU-E colony formation. CFU-E and CFU-G colony formation reducing the number of lympho-cytes showed a dose-dependent. Cyclosporine A can significantly increase the CFU-E and CFU-G colony forming rate. Conclusion This mouse model indicates that activated lymphocytes play important roles in marrow destruc-tion in lymphocyte infusion-induced BM failure. Only blocking the CD28/B7 signal transduction can not block the abnormal T-cells activated.

Objective To observe the expression and transcription of MART-1 in human uveal melanoma cell lines 92-1,92-2,Ocm3,Me1285,as well as the possible effect ofmethylation on its expression.Methods The cell lines 92-1,92-2,Ocm3 and Me1285 were cultured routinely and tested for MART-1 expression at protein and mRNA level by FACS analysis,Western blot and RT-PCR respectively.Methylation status of the MART-1 promoter region in all the cell lines were checked by Southern blots of DNA digested with methylation sensitive restriction enzymes.Results As observed in FACS analysis and Western blot,92-1,92-2 and Ocm3 were MART-1 positive cell lines while Me1285 was negative cell line.Consistent with protein analysis,92-1 and Ocm3 cell lines showed MART-1 specific PCR products and there was no product in Me1285 cell line in RT-PCR.The MART-1 positive cell lines,92-1,92-2,and Ocm3 show methylation at the MspⅠ/Hpa Ⅱ site,and the Nru Ⅰ sites of all positive cell lines are not methylated.The MART-1 negative cell line Me1285 shows hyperrnethylation at the Nru Ⅰ site and the Msp Ⅰ/Hpa Ⅱ site is not methylated.Conclusions MART-1 could be expressed in human uveal melanoma cell lines 92-1,92-2 and Ocm3.The change of methylation status of MART-1 promoter may correlate with the transcription of MART-1.

Objective To explore the effects of physiological deep-sea water(PDSW) on hyperthermal tolerance of Kunming (KM ) mice in the 45 .0 ℃ environment .Methods Deep-sea water from the south Chinese sea was processed ,and the metallic ele-ments dissolved in the DSW were analysed .The mice were randomly divided into 2 groups :the control group received tap water ;the experimental group treated with PDSW for 15 d .And then the mice were fed in the 45 .0 ℃ conditions .The survival time and histo-morphometric analyses of the brain ,lung ,heart ,liver and kidney were investigated .Results The survival time in PDSW-fed group was significantly longer than that of the control group (P< 0 .05) .Moreover ,histomorphometric analyses showed that PDSW could protect the brain ,lung ,heart ,liver and kidney of KM mice from the 45 .0 ℃ conditions .The results of western blot revealed that ex-pression of HSP72 of liver tissues for PDSW-fed group substantially increased ,when compared with the control mice(P< 0 .05) . Conclusion PDSW could improve hyperthermal tolerance of KM mice ,which maybe in the relation with expression of HSP72 pro-moted by PDSW .

Objective To investigate image quality and clinical value of dual-source dual energy virtual non-contrast (VNC) CT of the head. MethodsSixty-two patients suspected of cerebrovascular diseases underwent conventional non-contrast (CNC) CT and dual energy CTA examination of the head with dual-source CT. Virtual non-contrast images were reconstructed using dual energy software. The CT values of gray matter, white matter, cerebrospinal fluid, hyperdense hemorrhagic lesion and hypodense ischemic lesion were compared between CNC and VNC images. A four-score scale was used to assess image quality subjectively. Image noise, radiation dosage and detection rate were compared between CNC and VNC images. Paired t test, Wilcoxon signed ranks test and Chi-square test (McNemar test and Kappa test) were used. Results The CT value on CNC and VNC images, were (43. 3 ± 1.5) and (33. 2 ± 1.3) HU for gray matter (t = 46.98, P ＜ 0. 01), (32. 9 ± 1.3) and (28.8 ± 1.6) HU for white matter(t = 16. 28, P ＜0.01), (9.0 ± 1.4) and (5.3 ± 1.9) HU for cerebrospinal fluid (t=12.41, P＜0.01),(62.8 ±10.0) and (51.3 ± 11.5) HU for hyperdense lesion (Z = -4.37, P ＜ 0.01), (20.7 ±4.7) and (18.0 ±6. 9) HU for hypodense lesion (t = 3. 84, P ＜ 0. 01), respectively. VNC images[(1.63 ±0.34) HU]had more noise than CNC images[(0.99±0.18) HU](Z= -6.41, P＜0.01). VNC [(0. 53 ± 0. 08) mSv]had less effective dose than CNC[(1.37 ± 0. 23) mSy](Z= - 6. 45, P ＜ 0. 01).In subjective assessment, VNC images had more noise (2. 7 ± 0. 5 for VNC and 3.9 ± 0. 3 for CNC,Z = -6. 84, P ＜ 0. 01) and skull base-related artifacts (2. 4 ± 0. 9 for VNC and 3.7 ± 0. 5 for CNC,Z = -6. 15, P ＜0. 01) than CNC images. The gray/white matter contrast (1.3 ± 0. 5 for VNC and 3.3 ±0. 6 for CNC, Z = - 7. 01, P ＜ 0. 01), hyperdense lesion display (3.0 ± 0. 4 for VNC and 4. 0 ± 0. 0 for CNC,Z = -4. 52, P ＜ 0. 01) and hypodense lesion display (3.2 ± 0. 8 for VNC and 3.9 ± 0. 3 for CNC,Z= -3. 12, P ＜0. 01) on VNC images were lower than those on CNC images. In per-patient analysis,29 cases of hyperdense lesion (hemorrhage) were found on VNC images without misdiagnosis. The sensitivity, specificity, positive predictive value and negative predictive value were all 100. 0% (29/29,33/33, 29/29, 33/33). VNC images had the same detection rate of hyperdense lesions as CNC images (P ＞0. 05, Kappa = 1. 000) at per-patient level. Twenty-two patients with hypodense ischemic lesions were found on VNC images with one false positive case and two false negative cases. The sensitivity,specificity, positive predictive value and negative predictive value were 91.3% (21/23), 97.4%(38/39), 95.5% (21/22) and 95.0% (38/40) respectively. No statistical difference was found in detecting hypodense lesions between VNC and CNC images (χ2 = 0. 00, P ＞ 0. 05, Kappa = 0. 895). In per-lesion analysis, 53 hemorrhage lesions were found on VNC images with false negative results of four lesions and no false positive result. The sensitivity, specificity, positive predictive value and negative predictive value were 93.0% (53/57), 100. 0% (38/38), 100. 0% (53/53) and 90. 5% (38/42)respectively. There was no significant difference in detection rate of hyperdense lesion between VNC and CNC images (χ2 =2. 25, P ＞0. 05, Kappa =0. 914). Thirty-eight hypodense lesions were found on VNC images with 2 false positive lesions and 13 false negative lesions. The sensitivity, specificity, positive predictive value and negative predictive value were 73.5% (36/49), 96.4% (53/55), 94. 7% (36/38)and 80. 3% (53/66) respectively. The detection rate of hypodense lesion on VNC images was lower than that on CNC images (χ2 = 6. 67 ,P ＜ 0.01, Kappa = 0. 707). Conclusion Compared with CNC images,head VNC images have reduced image quality and radiation dosage. VNC images can replace CNC images potentially in detecting intracranial hemorrhage and provide information for ischemic cerebrovascular diseases to some extent.

Objective To investigate the adrenal steroidogenic function in genotype-proven heterozygotes carrying mutations in CYP17A1 gene in vivo. Methods Eight patients and 14 family members from 5 families with 17-hydroxylase/17,20-lyase deficiency (17OHD) were recruited. The mutations of the CYP17A1 gene in these individuals were screened by direct sequencing of PCR products. The hormonal response to ACTH was evaluated in the 14 genotype-proven carriers and 45 age- and sex-matched normal subjects. Results Three mutations were found in 5 unrelated families. 14 carriers with CYP17A1 mutation were identified, including 7 heterozygotes with D487_F489del, 6 with Y329fs, and 1 for H373L. Compared to the normal subjects, the carriers exhibited lower basal and ACTH-stimulated cortisol levels, but higher ACTH-stimulated corticosterone level. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of normal individuals at baseline and following ACTH-stimulation. Similarly, progesterone level and ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than that of normal individuals before and after stimulation. No significant differences were observed in the hormone levels between two genotypes (D487_F489del vs Y329fs). Conclusions Genotype-proven carriers of 17OHD without apparent clinical symptoms exhibit decreased enzyme activity,analogous to mildly impaired adrenal 21-hydroxylase activity in the carriers of CYP21 A2 gene mutation.

An expert consensus about the clinical diagnosis and treatment of dry eye was documented in 2013 by a corneal expert group of Chinese Ophthalmological Society.However, due to the rapid development of diagnostic and therapeutic devices of dry eye, researoh on dry eye has made significont progress in China since then.Consequently, the existing expert consensus cannot meet the needs of clinical practice.It is therefore urgent to develop a series of standardized diagnosis and treatment protocols, and publish a new consensus of experts and an operating guideline.At the same time, basic, clinical, and translational research on dry eye should be promoted to provide better services to the patients with dry eyes.On January 12, 2019 many experts in the field of dry eye in China held a panel discussion of dry eye study in Guangzhou to analyze the current development status and trends in the field of dry eye in China and abroad.In that meeting, opinions and recommendations were put forward based on a new understanding of the definition of dry eye, new concepts of dysfunctional dry eye, advances its diagnosis and classification, refinement and standardization of dry eye treatment, and the future development of dry eye research.

Objective:To explore the clinical features of acute diquat (DQ) poisoning, and further improve the awareness of acute DQ poisoning.Methods:A retrospective analysis was performed on the clinical data of patients with acute DQ poisoning diagnosed in the emergency department of the Second Hospital of Hebei Medical University from January 1, 2019 to December 31, 2021. The clinical data included age, gender, exposure routes, presence of pesticides (drugs) mixture poisoning, dosage of poison, the time from taking poisoning to admitting in the emergency department, clinical manifestations, laboratory data, treatment, hospital days, prognosis and survival days.Results:The number of cases who firstly complained of acute DQ poisoning in the past three years were 19 cases in 2019, 28 cases in 2020, and 51 cases in 2021. A total of 12 patients were excluded due to being diagnosed paraquat (PQ) poisoning by toxicology detection. Finally, 86 cases of acute DQ poisoning were included, including 80 cases of oral DQ poisoning, 1 case of intramuscular injection, 1 case of binocular contact and 4 cases of dermal exposure. In 80 cases of oral DQ poisoning, there were 70 cases of diquat poisoning alone (42 cases survived, 28 cases died) and 10 cases of pesticide mixture poisoning (6 cases survived, 4 cases died). The time from oral poisoning to admitting in the emergency department was 0.5-96.0 hours, with an average of (8.6±5.8) hours. The time of intramuscular injection poisoning to admitting in the emergency department was 3 hours. The time of dermal exposure to admitting in the emergency department was relatively long, with an average of 66.1 hours. The time from oral simple DQ poisoning to death was 12.0-108.0 hours, and the time from oral mixed DQ poisoning to death was 24.0-576.0 hours. A total of 70 patients with oral diquat poisoning alone presented various degrees of multiple organ injuries. All patients presented gastrointestinal symptoms such as nausea and vomiting. Renal injury and central nervous system injury were the most significant and closely related to the prognosis.Conclusions:Acute oral DQ poisoning can cause to multiple organ injuries, and the clinical manifestations are related to the dose of the poison. In severe cases, acute renal failure and refractory circulatory failure occur within 24 hours after poisoning, and severe central nervous system injury with disturbance of consciousness as the primary manifestation occurs within 36 hours, followed by multiple organ failure until death.

Objective To study the mechanism of paraquat (PQ)-induced renal injury in rats,the expression changes of ICAM-1 to assess the protective effect of Melatonin in PQ poisoning.Methods Ninety adult healthy Sprague-Dawley (SD) rats were divided into three groups at random.Control group:30 rats;Poisoned group:30 rats;Melatonin group:30 rats.Control group and Poisoned group were treated intragastrically with 1 ml of PQ (50 mg/kg) diluted with normal saline.Control groupwere treated with the same dose of normal saline as Poisoned group and Melatonin group.Melatonin group were given 1 ml of Melatonin at a dose of 10 mg/kg diluted with normal saline (once daily,intraperitoneally) Control and Poisoned group were treated with the same dose of normal saline (once daily,intraperitoneally) as Melatonin group.Pathology of renal tissue were oberserved by HE staining,and electron microscope.The histopathological changes and the expression of ICAM-1 were observed with mmunohistochemistry (IHC).Results (1) There were no obvious pathological changes in Control group.Poisoned group Renal glomerulus had hyperemia and distension.Renal tubule epithelial cell had edema and vacuolar degeneration and renal tubule lumina was narrowing on day 1,There were serious edema exudation and necrosis on day 5,which gradually lessened furthermore;Compared with Poisoned group,the aforementioned pathological lesion was more palliative in Melatonin group.(2) No obvious abnomal changes in ultrastructure of renal tissues in Control group.There were swelling of mitochondrion and rupture of renal tubule epithelial cell and endoplasmic reticulum had extension,lysosome was mult and had much phagocytosis in Poisoned group.(3)There was a very weak expression of ICAM-1 in Control group.while in Poisoned group,there was already a significant higher expression of ICAM-1 of renal tubule on day 1 after PQ poisoning,Immunohistochemistry score (IHS) of Poisoned group on day 1,3,5,7,14 were (0.1561 ±0.0295、0.2572±0.0259、0.3028±0.0153、0.2083 ±0.0227、0.9309 ±0.0059),compared with Control group (P＜0.01);Melatonin group were (0.1259±0.0061、0.2109±0.0280、0.2679±0.0233、0.1771 ±0.0186、0.0791 ±0.0135),compared with Control group (P＜0.01),compared with Poisoned group (P＜0.05);Conclusion ICAM-1 was involved in the procedures of renal injury;MT surely had a protective effect,which might be mediated by ICAM-1 in the paraquat-induced renal injury,but its regulation path still need a further exploration.

This paper analyzed the clinical data of a patient with acute oral emamectin·chlorfenapyr poisoning, and discussed the effect of blood purification therapy on chlorfenapyr poisoning. Chlorfenapyr was detected in the blood, urine, ultrafiltrate and plasma exchange fluid of the patient, and the concentrations of chlorfenapyr poison gradually decreased with time. Blood purification has a certain effect on chlorfenapyr, and early blood purification may be an effective measure to treat chlorfenapyr poisoning.