Objective To observe the changes in the pathological diagnosis rate of Graves'disease(GD) and Hashimoto's thyroiditis(HT)in the past 28 years and to probe its relationship to the environmental factors. Methods Statistic analysis was performed on data of thyroid disease,GD,HT and the complications of HT in Department of Pathology(1978-2005)in General Hospital of Tianjin Medical University with Run test,Cox-stuart test,ANOVA,t or t'test and Chi-square test.Results In 28 years there were 243 403 biopsies(average 8 693/ year)including 6 771 cases of thyroid disease(27.8‰),216 cases of GD(0.89‰),352 cases of HT (1.45‰).The biopsy rate of thyroid disease and GD showed a descending tendency since 1982 but an ascending tendency from 1995,furthermore,with GD it showed a descending tendency from 2001 to 2005 once more.While the biopsy rate of HT and GD+HT showed a descending tendency from 1986 and an ascending tendency after 1996,being 1-4 years later than thyroid disease and GD.The biopsy rate of GD+HT and the proportion of HT showed a descending tendency in 2002-2005 and 2003-2005 respecitvely.The average age of total and female patients with GD showed a descending tendency from 1997.The average age of GD was 13.7 years younger than HT,the patients of GDⅠ-type andⅡ-type being younger thanⅢ-type.The average age of lymphoid type(L), oxyphilie epithelium type(O),pronounced epithelium destruction type(P)in HT increased sequentially.In 28 years,there were more female patients with GD and HT,especially with HT.There existed 7.95% hyperthyroidism,6.25% nodular goiter,2.27% carcinoma in HT(more in L-type)and 2.56% hypothyroidism in HT(more in P-type).Conclusion Within 28 years,according to the pathological diagnosis rate,GD,HT,and GD+HT showed phasic tendencies related to drinking low iodine water and the implement of universal salt iodization policies in 1994 and 2000.Therefore,on the levels of genetics and environment,the factors that influence autoimmunity of thyroid gland could not exclude the variations of iodine intake,infection,affection or emotional stress.The mechanism of the changes in the pathological diagnosis rate needs further study.

AIM:To study the direct reprogramming method of mouse embryonic fibroblasts (MEFs) conver-ted into induced neural stem cells (iNSCs).METHODS:Sox2-infected MEFs were cultured in NSCs culture medium for 10 d.Subsequently , repeated suspension and adherent culture were performed for 3 times for the purification of iNSCs .The iNSCs were cultured in suspension medium .Real-time PCR was used to detect the expression of neural stem cell marker genes and pluripotent marker gene .In vivo, iNSCs were microinjected into the mouse cerebral cortex .Immunofluorescence was performed to detect the expression of neural stem cell , neuron, oligodendrocyte and astrocyte markers in vitro and vivo. RESULTS:A variety of neural stem cell marker gene expression was significantly increased in iNSCs detected by real -time PCR.Immunofluorescence confirmed that iNSCs expressed nestin and differentiated into neurons , oligodendrocytes and as-trocytes in vitro and vivo.CONCLUSION:Sox2 is sufficient to trigger the direct reprogramming from MEFs to iNSCs .iN-SCs have the ability of self-renew and 3 differentiation potentials in vivo and vitro.iNSCs are the suitable seed cells of SCI .

Objective To investigate the efficacy and safety of aminophylline,caffeine citrate and aminophylline combined with naloxone in prevention of apnea of prematurity(AOP).Methods Ninety-four infants with a birth weight ＜ 1 500 g and gestational age ＜ 34 weeks admitted to Department of Pediatrics,Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan.2010 and Jan.2012 were randomly divided into 3 groups.(1) Aminophylline group (n =30):30 infants received a loading dose of 4-5 mg/kg of aminophylline and then maintained by a dose of 2 mg/kg,with intravenous drip q12 h.(2) Caffeine citrate group(n =32):a loading dose of 20 mg/kg of caffeine citrate was followed by a daily maintained dose of 5 mg/kg,with intravenous drip per day.(3) Aminophylline combined naloxone group (observation group,n =32):32 infants were treated with Aminophylline combined with naloxone.After 6 hours of the first dose of aminophylline,a dose of 0.1 mg/kg naloxone was injected,q12 h.Then the two drugs were used alternately.The mortality and incidence of AOP,bronchopulmonary dysplasia(BPD),retinopathy of prematurity (ROP) and brain injury were evaluated,and drug-related side effects were recorded.Results 1.There was no significant difference in gender,gestational age,birth weight,maternal antenatal glucocorticoid application,pregnancy (including multiple pregnancy) and delivery,5 min Apgar score,oxygen therapy,and the application of positive airway pressure as well as pulmonary surfactant among the 3 groups(all P ＞0.05).2.Compared with aminophylline group,the incidence of apnea of caffeine group and observation group were significantly lower (F =6.704,P ＜ 0.05),but there was no significant difference between caffeine group and observation group (P ＞0.05).3.There was no statistically significant difference in mortality,duration of oxygen therapy,the incidence of ROP,brain injury and hearing loss,postmenstrual age,body weight at discharge,the duration and cost of hospitalization among the 3 groups(all P ＞0.05).4.The BPD incidence in caffeine group[9.4％ (3/32 cases)] and observation group [12.5％ (4/32 cases)] were lower than that in Aminophylline group [20.0％ (6/30 cases)],but there was no statistical significance among the 3 groups(P ＞ 0.05).5.No drug-related side effects were recorded in the 3 groups.Conclusions It is safe and effective to use aminophylline combined with naloxone in prevention of AOP,and its efficiency is similar to caffeine citrate.

To investigate role of Notch1 - 3 in hyperoxia-induced lung injury in newborn rat exposed to 85% O2, SD rat litters born on the 22th day were randomly divided into two groups: room air group and hyperoxia group. The animals were sacrificed 1, 4, 7, 10, 14 and 21 days after continued exposure to oxygen (n = 40, oxygen > 0.85) or room air (n = 40). 6 rats each group were used to assess lung histological changes by HE staining and expression of Notch in lungs by immunohistochemistry. Total RNA was extracted by Trizol reagent from frozen lung tissues. Notch mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). Our results showed that 7, 14 and 21 days after O2 exposure, hyperoxia group showed lung injury characterized by pulmonary edema, hemorrhage and lung development arrest. Positive staining for Notch1, Notch 2 in hyperoxia group was much lower than those in room air group at all time points (P < 0. 01, P < 0.05), but compared with the controls, the hyperoxia group showed higher expression of Notch3 (P > 0.05). Immunostained cells were typically airways epithelia, alveolar epithelial and inflammatory cells, and fibroblasts in hyperoxia group (P < 0.01). Notch mRNA levels showed similar change as protein level (P < 0.01). It is concluded that the prolonged exposure to 85% O2 resulted in abnormal expression of Notch receptors, which might contribute to the pathogenesis of hyperoxia-induced lung injury in newborn rats. The decreased inhibition of Notch1 might be one of the protective reaction and major mechanisms for proliferation/differentiation of type II alveolar epithelial cells. The up-regulation of Notch3 activity might result in the lung development arrest of the newborn rats.
Aerobiosis ; Animals, Newborn ; Lung/*pathology ; Lung Diseases/etiology ; Lung Diseases/*metabolism ; Lung Diseases/pathology ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Random Allocation ; Rats, Sprague-Dawley ; Receptors, Notch/*biosynthesis ; Receptors, Notch/genetics

This study examined the effects of retinoic acid (RA), PD98059, SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-2 (TIMP-2) in premature rat lung fibroblasts (LFs). LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 (ERK1/2), SP600125 (JNK1/2) and SB203580 (p38) respectively. The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 activity was measured by zymography. The amount of p-ERK1/2, REK1/2, p-JNK1/2, JNK1/2, p-p38 and p38 was determined by Western blotting. The results showed that: (1) PD98059, SP600125 and SB203580 significantly inhibited p-ERK1/2, p-JNK1/2 and p-p38 respectively in LFs; (2) The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA, SP600125 and SB203580 respectively (P<0.01 or 0.05), but did not change after treatment with PD98059 (P>0.05). Meanwhile, RA, PD98059, SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia (P>0.05); (3) The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air (P>0.05), but decreased remarkably after hyperoxia (P<0.01 or 0.05). SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia (P<0.01). PD98059 exerted no effect on the expression of pro- and active MMP-2 (P<0.05). It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia.

Objective To investigate the diagnosis,treatment and prognosis of neonates with severe acute respiratory distress syndrome (ARDS) according to Berlin definition.Methods A retrospective study was carried to analyze the clinical features about diagnosis,treatment,chest X-ray findings,mortality,complications and ventilator parameters in 86 neonates with severe ARDS admitted in the NICU from January 2005 to December 2013.Results (1)Among the 86 cases,55 were cured,and 31 died with 36.0％ mortality.(2) Chest X-ray showed there was decreased lucency of bilateral lungs with ground-glass appearance,lung texture with thick chaos or dot flakes or patchy shadows in 36 neonates; diffuse infiltrates and extensive confluent consolidation shadows in bilateral lungs along with peripheral air brornchograms in 26 cases; heart shadow and diaphragmatic surface disappeared like a white lung change in 24 cases.(3) Persistent pulmonary hypertension of newborn as a complication occurred in 68 cases with 79.1％ incidence.(4) Eighty-six cases were categorized into survival group and death group.The results showed compared with the survival group,the neonates in death group required higher FiO2,and PaO2,and lower PaO2/FiO2 before mechanical ventilation (P ＜ 0.01),but needed higher initial PIP of mechanical ventilation (P ＜ 0.01).Conclusions Neonatal ARDS is still a kind of critical condition with high mortality and lack of evidence-based diagnostic criteria so far.The therapeutic strategy for neonatal ARDS should be a comprehensive measures in addition to appropriate respiratory support.

Novel oneogene with kinase-domain (NOK) can activate multiple mitogenic signaling pathways including the janus kinases(JAK) and signal transducer and activator of transcription proteins (STAT). It was showed that NOK specifically and physicallyinteracted with STAT3 in human embryo kidney 293T (HEK293T) cells. In addition, NOK could directly interact with most of the STAT3 subdomains except coiled-coil and C-terminal domains. Removing ectodomain and transmembrane domain of NOK markedly enhanced its intermolecular interaction with STAT3. Also, NOK could co-immtmoprecipitate with JAK2. in vivo. Importantly, co-expression of NOK and JAK2 produced a synergistic effect on NOK-mediated STAT3 activation, while inactivating the kinase domain of JAK2 completely prevented this synergistic effect. Overall, the results indicated that NOK might complex with both STAT3 and JAK2 and activate STAT3 signaling by a JAK2-dependent mechanism.

Objective To determine the dynamic changes in adenosine monophosphate-activated protein kinase (AMPK) in neurons of neonatal rats suffering from hypoxic ischemic brain injury.Methods Twenty-four-hour old and seven-day old neonatal rats were used in this study.A classic primary cortical neuron oxygen glucose deprivation (OGD) model and neonatal rat hypoxic ischemic encephalopathy (HIE) model were employed.Lactic dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were used to evaluate neuron viability and damage.The expression of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK),phosphorylated activated protein kinase (P-Akt) and Cleaved Caspase-3 in neurons and brain tissue was measured by Western blot at different time points after OGD or HIE.The Student-t test was used for statistical analysis.Results (1) Compared with the control group,LDH levels at 2,4,8 and 24 h after OGD were higher (all P＜0.05) and optical absorption levels of MTT were lower (all P＜0.05).(2) Levels of P-AMPK in the OGD group were higher than those in the control group,and showed a time-dependent increase at 30 min and 2,4,8 and 24 h (all P＜0.05).The expression levels of P-AMPK in the HIE group were higher than those in the control group (0.345 ± 0.038,0.387 ± 0.112 and 0.618 ± 0.075 at 1,3 and 7 days after HIE,and 0.132±0.032 in the control group,all P＜0.05).(3) The levels of P-Akt increased above the control levels at 30 min (0.991 ±0.134 vs 0.304±0.050),reached a maximum level at 2 h (1.183± 0.107),and then gradually declined,whereas the levels of Cleaved Caspase-3 started to increase at 30 min,and remained elevated at 24 h (all P＜0.05).Conclusion Following hypoxic ischemic brain damage,the expression of P-AMPK is significantly increased in both in vivo and in vitro studies in a time-dependent manner.

Objective: By taking the holism and differentiation concepts of traditional Chinese medicine (TCM) as the guidance, physical, mental and workplace factors were recruited in the observation of depression in employees, and were systematically classified to establish a workplace-related Liver Meridian-depression scale, for providing an evaluation index for depression in employees. Methods: NVIVO 11 software was adopted to assort ancient TCM classics. Based on the holism and differentiation concepts of TCM and well-developed scales, the item pool was determined via brain storm and screened by Delphi method after classified; a Wechat questionnaire was handed out 240 times via the online system 'Wen Juan Xing', and the results were statistically analyzed by the SPSS 17.0 version software. Results: Five dimensions consisting of 80 items were obtained after classification, and 60 items were selected by Delphi method; a total of 216 questionnaires were returned and the return rate was 90%. Of which, 215 questionnaires were valid ones, and the valid rate was 99%. By exploratory factor analysis (EFA), 44 items were obtained, and the aggregate split-half reliability coefficient was 0.922. The Cronbach's alpha coefficient for the five dimensions, i.e. Liver Meridian, relevant meridians, basic psychological activities, work cognition and emotional reactions, was respectively 0.841, 0.842, 0.914, 0.836 and 0.839, indicating a content internal consistency. The score of each item was highly correlated with the corresponding dimension, and the intercommunity was between 0.474 and 0.801. Nine factors were generated, 2 in the dimension of Liver Meridian, 3 in the dimension of relevant meridians, 2 in the dimension of basic psychological activities, 1 in the dimension of work cognition, and 1 in the dimension of emotional reactions, and the load of each factor was between 0.438 and 0.859. The reliability and validity of the scale were well examined. Conclusion: The scale can be applied to evaluate the qi activities of Liver Meridian and depression symptoms related to workplace.

Objective To explore the value of virtual touch tissue imaging (VTI) of acoustic radiation force impulse (ARFI) elastography in the differential diagnosis of benign and malignant thyroid nodules.Methods VTI features of 77 histologically proven thyroid nodules in 74 patients were analyzed and the VTI features were divided into 6 grades.The higher grade represented higher tissue stiffness.Differences in VTI grade between benign and malignant lesions were analyzed by receiver operator characteristic (ROC) curve,and the sensitivity,specificity and accuracy were calculated.Results 77 pathologically proven thyroid nodules included 61 benign and 16 malignant lesions.VTI images classification included 0 in grade Ⅰ,1 ingrade Ⅱ,1 in grade Ⅲ,9 in grade Ⅳ,3 in grade Ⅴ and 2 in grade Ⅵ for malignant diseases ; and included 18 in grade Ⅰ,28 in grade Ⅱ,10 in grade Ⅲ,1 in grade Ⅳ,2 in grade Ⅴ and 2 in grade Ⅵ for benign diseases.The best diagnostic point of VTI-grade was grade Ⅳ.When VTI-grade Ⅳ or greater was used as the diagnostic criterium for malignancy,the sensitivity,specificity and accuracy rate in differentiation between benign and malignant thyroid nodules were 87.50％,91.80％ and 90.9(％ respectively.Conclusions VTI is useful in the differential diagnosis between benign and malignant thyroid nodules.