Expression characterization of MANF during course of rat adjuvant arthritis and its relationship with inflammation / 中国药理学通报

Aim To observe the expression of mesen-cephalic astrocyte-derived neurotrophic factor(MANF) in synovial membrane and serum of rats with adjuvant arthritis (AA) and to analyse the relationship between MANF expression and arthritis. Methods AA models were prepared by injecting Freund complete adjuvant (FCA) into SD rats. The swelling of the secondary joint was measured by foot volume measurement. The severity of AA was recorded by arthritis index (AI). Synovial pathological changes were observed by HE staining. The protein and mRNA levels of MANF,BiP and CHOP extracted from synovial tissues in different periods of AA rats were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The levels of MANF, C-reactive protein (CRP), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in serum were detected by enzyme-linked immunosorbent assay (ELISA) and then the relationship between MANF level and inflam-matory factors were explored. Results AA rat model was established successfully. The expression of BiP significantly increased in synovial tissue on d 2 after CFA injection,and decreased until d 28. The expres-sion of MANF slightly increased on d 2,then remained stable,and significantly increased on d 14, and then decreased gradually. The expression of CHOP kept to rise slowly at a low level. The level of MANF in serum markedly increased on d 14,then gradually decreased, but it was still higher than the normal level on d 28. The level of CRP exhibited similar trend with MANF. Correlation analysis showed that MANF had a negative correlation with arthritis symptoms, IL-1β and TNF-α in the secondary inflammatory period of AA rats. Con-clusions Arthritis induces the expression and secre-tion of MANF,and the level of MANF is closely relat-ed to the progression and severity of arthritis.

An online survey on iodine deficient disorders knowledge and its control in urban doctors and nurses / 中华地方病学杂志

Objective To understand the awareness level of iodine deficiency (ID) impairments and the attitude on edible iodized salt,and its consumption among doctors and nurses in cities,in order to provide scientific evidence for health education on iodine deficient disorders (IDD) in the future.Methods The questionnaire was self-designed,and spread through the web page of Wenjuanxing,an online server company,from May 6 to June 6,2017.At the end of the survey,a total of 481 valid questionnaires were reclaimed,in which ratio of gender was female 63.8％ (307/481),male 36.2％ (174/481).The data were analyzed by SPSS 22.0,including logistic regression analysis with backward according to the statistical significant level of P ＜ 0.05.Results Among doctors and nurses,90.4％ (435/481) knew ID impairments;72.8％ (350/481) answered intelligent disability as the most serious problem of ID;55.5％ (267/481)misunderstood that the areas in which they lived were not ID areas,although all cities surveyed were ID areas;41.0％ (197/481) of doctors and nurses misunderstood that coastal residents did not need to consume iodized salt.About the evaluation of iodine nutrition status of current population,15.6％ (75/481) of respondents judged as iodine excess.About consuming edible salt,76.3％ (367/481) selected iodized,9.6％ (46/481)non-iodized,and 14.1％ (68/481) both iodized and non-iodized.The results of logistic regression analysis showed the factors that prevents health care workers from choosing iodized salt were:"living in coastal areas","think him or her as iodine adequate","know that iodine deficiency can affect the development of children but still adhere to the consumption of non-iodized salt";the factors that promoted the choice of iodized salt for medical staff were "insist on buying iodized salt,and do not choose non-iodized salt",and 75.8％ (238/314)of them knew that intelligent disability as the most serious problem of ID.Conclusions Most doctors and nurses have high level of knowledge on ID and its control.But lack of information,as well as misunderstanding of "coastal areas iodine adequate" and worry about "excess iodine causes thyroid diseases and cancer",which would hinder the active consumption of iodized salt.Health education for them should be conducted through professional ways,stressing on the threaten of ID environment,sharing the information about national and local progress on control of IDD and iodized salt safety,and clarifying the relationship between iodine salt or iodine and thyroid cancer and nodules.

Observation on the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the best dose of methylprednisolone improving lung injury in swine with paraquat intoxication.</p><p><b>METHODS</b>Acute lung injury (ALI/ARDS) model was made by an intraperitoneal injection of a large dose of 20%PQ solution20 millilitres in swine. Then 24 swine were randomly divided into 4 groups: exposed PQ control group, 5 mg/kg of methylprednisolone group, 15 mg/kg of methylprednisolone group, 30 mg/kg of methylprednisolone group. All groups were based on the conventional rehydration for intervention, Arterial blood samples were collected before modeling and 0, 12, 24, 36 hours after different processing for blood gas analysis. At the same time heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were measured by using PICCO (pulse indicator continuous cardiac output), lung tissue was obtained by punctureneedle to produce lung biopsy, then observe the pathological changes of lung tissue in the microscope.</p><p><b>RESULTS</b>1. Comparison between groups: there is no significant difference about extravascular lung water index (EVLWI) and semi-quantitative score of lung tissue pathology in four groups (P > 0.05) before modeling, so is t0, there is significant difference at about extravascular lung water index and semi-quantitative score of lung tissue pathology 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: EVLWI and semi-quantitative score of Lung tissue pathology in four groups significantly increased when the model was made (P < 0.05), after different processing, EVLWI and semi-quantitative score of Lung tissue pathology in exposed PQ control group kept going up, in other three groups, EVLWI and semi-quantitative score of lung tissue pathology went down first and then went up, there is significant difference compared with t0 (P < 0.05). 2. Comparison between groups: there is no significant difference about oxygenation index in four groups (P > 0.05) before modeling, so is t0, there is significant difference about oxygenation at 12 h, 24 h and 36 h after different processing (P < 0.05). Within the group: oxygenation index in four groups significantly decreased when the model was made (P < 0.05), after different processing, oxygenation index in exposed PQ control group kept going down, in other three groups, it showed a downward trend after the first rise, there is significant difference compared with t0 (P < 0.05). 3. After medication for 36h, correlation analysis showed that EVLWI were negatively associated with oxygenation index (r = -0.427, P = 0.022) and positively associated with semi-quantitative score of Lung tissue pathology (r = 0.903, P = 0.034).</p><p><b>CONCLUSION</b>Methylprednisolone can obviously relieve lung injury caused by paraquat poisoning and improve oxygenation. After the model was made, within 24 hours, 30 mg/kg of methylprednisolone have advantage for the PQ poisoning swine, but 15mg/kg of methylprednisolone is best for improving lung injury induced by paraquat intoxication within 24 hours to 36 hours.</p>

Effects of anti-survivin oligonucleotides on growth of peritoneally implanted ovarian cancer xenografts in nude mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of anti-survivin oligonucleotides (ASODN) on the invasion and growth of peritoneally implanted ovarian cancer cell xenografts in nude mice.</p><p><b>METHODS</b>Nude mouse models bearing peritoneally implanted ovarian cancer cell (SKOV3) xenografts were established and subjected to intraperitoneal injection of survivin ASODN or saline (control). The number and weight of the intraperitoneal xenografts were compared between the two groups.The expressions of interleukin (IL-6), signal transducer and activator of transcription3 (STAT3), phosphorylated STAT3 (p-STAT3), and survivin protein in the tumor tissues were detected with Western blotting in both groups.</p><p><b>RESULTS</b>Compared with those in the control group, the number and weight of the intraperitoneal xenografts were significantly reduced in ASODN group (P<0.05). ASODN treatment also resulted in significantly lowered protein levels of IL-6, STAT3, p-STAT3, and survivin in the tumor tissues (P<0.05).</p><p><b>CONCLUSION</b>Survivin ASODN can suppress the invasion and migration capacity of ovarian cancer cells and inhibit peritoneal metastasis of the tumor in nude mice possibly though down-regulation of IL-6/STAT3 signaling pathway.</p>

Joint effects of hydroxyethyl starch and furosemide on acute lung injury induced by paraquat in swine / 中华急诊医学杂志

Objective To discuss the jointly therapeutic effects of 6％ hydroxyethyl starch 130/0.4 (voluven) and furosemide on acute lung injury induced by paraquat (PQ) in swine.Methods The ALI/ ARDS models were established with 20％ PQ (20 mL) intraperitoneal injection in 18 healthy female piglets and randomly divided into three groups: voluven group (A), furosemide group (B) and voluven + furosemide group (C) (n =6 in each group).The heart rate (HR), mean arterial pressure (MAP), extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), partial pressure of carbon dioxide (PaCO2) and oxygenation index (PaO2/FiO2) among the three groups were carefully measured by PICCO (pulse indicator continuous cardiac output) before modeling (baseline), just aftermodeling (t0), and 2 h (t2), 4 h (t4), 6 h (t6) and 8 h (t8) after trearment.Needle biopsies of lung tissue were made before modeling and at t0 and t8 and prepared for microscopy observation after Hematoxylineosin staining method (HE staning).Repeated measurement data were compared among repeated measures by the ANOVA and the difference between groups was compared by one-wey ANOVA.Results (1) The HR and MAP of all animals increased obviously while the oxygenation index declined significantly at modeling just made (t0) compared to those before modeling (all P ＜ 0.05).At the same time, the HR and MAP of A and B groups were significantly lower than those of C group after treatment (all P ＜ 0.05), while the oxygenation index of A and B were significantly higher (all P ＞ 0.05).(2) The ELWI and PVPI of all animals increased obviously at modeling just made (t0) compared to those before modeling (all P ＜ 0.05).The ELWI and PVPI were decreased after treatment.And at the same time, the ELWI and PVPI of A and B groups were significantly lower than those of C group after treatment (all P ＜ 0.05).(3) The alveolar tissue showed obviously injured changes at modeling just made (t0).The injury was relieved 8h after trearment, which was most markedly in group C.Conclusions With the combination of 6％ hydroxyethyl starch 130/0.4 and furosemide administered, the acute lung injury induced by paraquat poisoning can be effectively relieved, promoting gas exchange, and improve oxygenation.

Experimental design on flow characteristics of aqueous humor based on PIV method / 医用生物力学

Objective To visualize the process of introcular flow caused by injection into the posterior chamber of the impermeable vitro eyeball with particle image velocimetry (PIV) technology, and calculate the flow fields at different moments, so as to investigate PIV experimental scheme for low-speed flow field measurement in the eye and provide basis for the in vivo measurement of aqueous humor flow under physiological status. Methods In an impermeable vitro eyeball, the introcular flow would be slow enough when the injection pump was driven at the rate of 0.2, 0.4, 0.6, 0.8, 1.0, 1.5 mL/min. Fluorescent particle solution, with a certain concentration and particle diameter of 10 μm, was injected into the posterior chamber of the vitro rabbit eye, and the sheet laser was projected to the medial frontal plane of the eye. Then clear particle images were captured by camera, and the velocity field was recorded and calculated by PIV system. Results The fluid into the posterior chamber first filled in the posterior chamber and the pupil, then passed the pupillary margin and flowed into the anterior chamber, which was consistent with the theoretical flow process of aqueous humor under physiological conditions. Based on analysis of the particle images, the velocity inside an impermeable eyeball was calculated at the magnitude of a few millimeters per second. Conclusions PIV method can be applied to low-speed flow field measurement, and the flow characteristics inside the eyeball can also be measured by PIV method, which contributes to the measurement of aqueous flow under both physical and pathological conditions, provides experimental verification for numerical simulations on aqueous humor field, and offers a new diagnostic and treatment perspective for shear force damage and destructions of corneal endothelial cells, the iris and lens under different flow fields.

Ulinastatin attenuates paraquat-induced myocardial injury / 中华急诊医学杂志

Objective To investigate the effect of ulinastatin (UTI) on endogenous antioxidant systems in the process of myocardial oxidative stress injury induced by paraquat (PQ),so as to elucidate UTI protecting cadiocytes against PQ-induced injury.Methods Thirty Japan white rabbits were randomly (random number) divided into A,a sham control group; B,PQ intoxication model group and C,D,E,three UTI groups as per different dosages of UTI given.PQ (30 mg/kg) was administered by intraperitoneal route to the rabbits of PQ intoxication model and rabbits of three UTI groups.UTI in doses of 15 000,30 000,50 000 U/kg was administered intravenously every day to the rabbits of three UTI groups respectively for 7 days after PQ intoxication.After the rabbits were sacrificed with 10％ chloral hydrate,left ventricles of rabbits were taken.Histomorphological changes of myocardium were observed by using HE staining.Hydroxyproline was measured by alkaline hydrolysis method,myocardial oxidative stress evaluated by 4-hydroxy-2-nonenal (4-HNE) immunohistochemistry staining,transcription levels of transforming growth factor-β1 (TGF-β1),adiponectin,peroxisome proliferator-activated receptor α (PPAR-α),AMP-activated protein kinase-β1 (AMPK-β1),uncoupling protein-1 (UCP-1) were assayed with reverse transcriptionpolymerase chain reaction (RT-PCR).The differences between two groups were analyzed by t test ; for multiple comparisons,data were analyzed by One-Way ANOVA followed by Dunnett' s post hoc test; for two and multiple ranked data comparisons,Mann-Whitney U test and Kruskal-Wallis test were used,and Spearman rank correlation analysis was used to investigate the correlation between UTI dose and transcription levels of endogenous antioxidant.Results Compared with group A,left ventricular cadiocytes in group B became swelled and disarranged,concentration of tissue HYP was elevated to (2.37 ± 0.49),P =0.001;scores of 4-HNE and TGF-β1 mRNA expressions were all upregulated (both P =0.001).Compared with group B,disordered myocytes in UTI treated groups tended towards normal,4-HNE scores in group D and group E descended respectively to (1.83 ± 0.53) and (1.70 ± 0.47),both P =0.001,HYP concentration reduced to (3.51 ±0.39) μg/mg and (3.29 ±0.37) μg/mg (P =0.002; P =0.001),and expressions of TGF-β1 mRNA in these two groups were decreased (both P =0.001).Transcription levels of four endogenuous antioxidant components,adiponectin,PPAR-α,AMPK-β1 and UCP-1,were all augmented in the group E with high dose UTI.The mRNA expressions of these four components positively correlated with the dose of UTI in the myocardium of PQ intoxicated rabbits.Conclusions UTI could protect myocardia against PQ-induced injury by increasing endogenous antioxidant systems.

Clinical characteristics and survival of patients with pulmonary veno-occlusive disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the clinical presentation, diagnosis, treatment and outcome of patients with pulmonary veno-occlusive disease (PVOD).</p><p><b>METHODS</b>Data from patients diagnosed as PVOD from May 2008 to May 2011 in Shanghai Pulmonary Hospital, Tongji University were retrospectively reviewed.</p><p><b>RESULTS</b>During this period, 5 patients [4 female, aged from 12 to 42 (22 ± 12) years old] were diagnosed as PVOD. The durations from symptoms onset to PVOD diagnosis was 2 to 50 (16 ± 20) months and four of them were previously diagnosed as idiopathic pulmonary arterial hypertension. All patients at the time of PVOD diagnosis had a severely impaired WHO pulmonary hypertension functional class (3 in class III and 2 in class IV). Furthermore, all patients characterized by a typical sign of centrilobular ground-glass opacities in high-resolution computed tomography, a markedly reduction of diffusing capacity of the lung for carbon monoxide [(38 ± 12)% of predicted value] in pulmonary functional test and severely compromised cardio-pulmonary hemodynamics identified by right heart catheterization. All patients received conventional and pulmonary arterial hypertension specific therapies, and then followed-up regularly. Up to now, 4 out of 5 patients died due to refractory right heart failure. The durations from symptoms onset to death and from PVOD establish to death were 5 - 65 (27 ± 26) months and 1 - 16 (9 ± 9) months, respectively.</p><p><b>CONCLUSIONS</b>PVOD is a rare and malignant cardio-pulmonary disorder that often be misdiagnosed as idiopathic pulmonary arterial hypertension. Given the poor responses to modern pulmonary arterial hypertension specific therapies, lung transplantation remains the treatment of choice.</p>

Lysine acetylsalicylate ameliorates lung injury in rats acutely exposed to paraquat / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Paraquat (PQ), an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate (LAS) could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection.</p><p><b>METHODS</b>A model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ + LAS groups, with 25 in each group. We assessed and compared the malonaldehyde (MDA) content, superoxide dismutase activity (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) in serum and lung and the hydroxyproline (HYP) content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21 after PQ poisoning and LAS treatment.</p><p><b>RESULTS</b>Compared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning (all P < 0.05). After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced.</p><p><b>CONCLUSION</b>In this rat model of PQ poisoning, LAS effectively ameliorated the lung injury induced by PQ, possibly through antioxidation, anti-fibrosis, anti-apoptosis, and anticoagulation.</p>

PDK1 plays a critical role in regulating cardiac function in mice and human / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>PDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5. To elucidate the role of PDK1 in the heart, we investigated the cardiac phenotype of mice that lack PDK1 in the heart in different growth periods and the alteration of PDK1 signaling in human failing heart.</p><p><b>METHODS</b>We employed Cre/loxP system to generate PDK1(flox/flox): α-MHC-Cre mice, which specifically deleted PDK1 in cardiac muscle at birth, and tamoxifen-inducible heart-specific PDK1 knockout mice (PDK1(flox/flox):MerCreMer mice), in which PDK1 was deleted in myocardium in response to the treatment with tamoxifen. Transmural myocardial tissues from human failing hearts and normal hearts were sampled from the left ventricular apex to analyze the activity of PDK1/Akt signaling pathways by Western blotting.</p><p><b>RESULTS</b>PDK1(flox/flox): α-MHC-Cre mice died of heart failure at 5 and 10 weeks old. PDK1(flox/flox) -MerCreMer mice died of heart failure from 5 to 21 weeks after the initiation of tamoxifen treatment at 8 weeks old. We found that expression levels of PDK1 in human failing heart tissues were significantly decreased compared with control hearts.</p><p><b>CONCLUSION</b>Our results suggest that PDK1 signaling network takes part in regulating cardiac viability and function in mice, and may be also involved in human heart failure disease.</p>

Increased stromal-cell-derived factor 1 enhances the homing of bone marrow derived mesenchymal stem cells in dilated cardiomyopathy in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Stem cell transplantation has been shown to have beneficial effects on dilated cardiomyopathy. However, mechanism for stem cell homing to cardiac tissue in dilated cardiomyopathy has not yet been elucidated.</p><p><b>METHODS</b>Mesenchymal stem cells were obtained from rat bone marrow, expanded in vitro, and labeled with (99m)Tc. Cardiomyopathy model was induced by doxorubicin in rats. (99m)Tc labeled cells were infused into the left ventricles in cardiomyopathy and control rats. Sixteen hours after injection, animals were sacrificed and different tissues were harvested to measure specific radioactivity. By use of real-time polymerase chain reaction and immunohistochemistry, mRNA and protein expressions for stromal-cell-derived factor 1 in cardiac tissue were measured.</p><p><b>RESULTS</b>Labeling efficiency of mesenchymal stem cells was (70.0 ± 11.2)%. Sixteen hours after mesenchymal stem cell transplantation, the heart-to-muscle radioactivity ratio was increased significantly in cardiomyopathy hearts as compared to control hearts. Both mRNA and protein expressions of stromal-cell-derived factor 1 were up-regulated in cardiomyopathy hearts as compared with control hearts.</p><p><b>CONCLUSION</b>In dilated cardiomyopathy induced by doxorubicin up-regulated expression of stromal-cell-derived factor 1 in heart may induce mesenchymal stem cells home to the heart.</p>

Time Management Disposition and A-Type Personality in College Students / 中国临床心理学杂志

Objective: To investigate the relationship between college students' time management disposition and A-type personality. Methods: 320 college students were investigated by Time Management Disposition Scale and A-Type Personality Scale. Results: College students' personality types had positive correlation to their time management disposition.A-type students' time management disposition score was significantly higher than that of the B-type students'.Conclusion: College students' personality type had close relationship with their time management disposition.