Objective To investigate the mechanism of neuronal apoptosis in hippocampal CA1 region and the death signaling transduction pathway initiated by CD95(Fas) molecules during cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). Methods SAH model was developed by injecting arterial blood twice the citernamagna.The morphological changes of the neurons were studied by light microscope and laser scanning confocal microscope.RT-PCR was performed for detecting the expression changes of Fas,FasLmRNA. Results Neurons in the hippocampal CA1 region after SAH showed typical apoptotic features under light microscope and confocal microscope.The expressions of Fas,FasLmRNA in hippocampus increased in SAH group,reached the highest level 3 days after SAH and still were significantly higher 7 days after SAH compared with normal group and then decreased to normal 14 days after SAH.Conclusion The death signaling transduction pathway initiated by CD95 molecules may play important roles in hippocampus neuronal apoptosis following SAH.

Objective To summarize the clinical characteristics of patients with connective tissue diseases (CTD) and autonomic neuropathy. Methods The medical records of inpatients with CTD and autonomic neuropathy from 2005 to 2015 were retrospectively analyzed including clinical manifestations, laboratory examinations, treatment and outcome. Categorical data were expressed in percentages. Kolmogorov-Smirnov test was used to examine normal distribution. Continuous data of normal distribution were expressed as x ±s deviation, while data without a normal distribution were described as median and interquartile range (P25, P75). Results Among the nine patients included in this study, all were female, and the median age was 42 years (32~50 years old). Four patients (4/9) were systemic lupus erythematosus (SLE), three patients (3/9) were primary Sj?gren's syndrome (pSS), two patients (2/9) were rheumatic arthritis (RA), and four patients were secondary Sj?gren's syndrome (SS) (two with SLE and two with RA). Five patients (5/9) had autonomic nervous dysfunction before they were diagnosed of CTD, while four patients (4/9) developed autonomic nervous dysfunction after diagnosis of CTD. The most common symptom of autonomic nervous dysfunction was postural hypotension (9 patients, 9/9), followed by hypohidrosis (4 patients, 4/9), urinary retention (2 patients, 2/9), gastrointestinal dysmotility (2 patients, 2/9) and tonic pupil (1 patient, 11%). After treatment of CTD, autonomic symptoms of three patients improved, while the others didn't. Four of the remaining 6 patients improved after receiving other assistant treatments including vasoconstrictor, pyri-dostigmine bromide, and plasma exchange. Conclusion Patients with CTD could present with autonomic neuropathy, which is mainly characterized with postural hypotension. If patients had related symptoms, clinicians should pay more attention to whether CTD exists. If treatment for CTD couldn't improve patients' condition, other assistant treatment might be considered.

Background Diclofenac sodium eye drops,pranoprofen eye drops and bromfenac sodium hydrate eye drops are three clinical commonly used nonsteroidal anti-inflammatory drugs(NSAIDs).The variation of cytoxicity among these drugs and whether the cytoxicity is related to the supplements are also unknown.Objective This study was to compare the cytotoxicity of three non-steroidal anti-inflammatory eye drops and their active components with cultured human corneal epithelial cells (HCECs) in vitro,and to discuss toxic origins of these drugs.Methods HCECs were cultured in different drugs with the final concentration of 0.10％,0.05％,0.02％ and 0.01％.Cell proliferation was evaluated by MTT assay.Then,0.002％ eye drops (1∶50) was added,and the migration and damage of the cells were deceted by transwell migration assay and lactate dehydrogenase (LDH) assay.Results The cytotoxicity of three nonsteroidal anti-inflammatory eye drops on HCECs was concentration-dependent (all at P=0.00).Diclofenac sodium eye drops showed the most dominant effects on the proliferation,migration and damage of HCECs among the three eye drops,while bromfenac sodium eye drops showed the least effect on the cell damage (proliferation:Fdrug =20.25,P=0.00;migration:F =103.43,P =0.00;damage:Fdrug =164.16,P =0.00).Compared with the eye drops,their active components showed less cytoxicity.Pranoprofen appeared the least effects on the proliferation,migration and damage of HCECs (proliferation:Fdrug =332.27,P =0.00;migration:F =332.27,P =0.00;damage:Fdrug=154.83,P=0.00).Conclusions The cytotoxicity ofdiclofenac sodium eye drops is more obvious than that of pranoprofen eye drops or bromfenac sodium hydrate eye drops.The cytotoxicity of the three eye drops originates from their supplements or the interaction between the supplements and active components.

Objective To evaluate the influence of right ventricular outflow tract septal ( RVS) pacing with right ventricular apical ( RVA) pacing on left ventricular remodeling and brain natriuretic peptide ( BNP). Methods Sixty patients with indication of pacemaker implantation were randomized into two groups, RVA group and RVS group. BNP was measured with ELISA, and echocardiography was performed to measure the left ventricular end diastolic volume ( LVEDD), left ventricular end systolic volume ( LVEDV) and left ventricular ejection fraction (LVEF) at pre-operation,and after 6,12,24 months pacing. The difference of cardiac remodeling and BNP in the two groups was observed. Results Compared to BNP at pre-operation (( 60. 2 ± 15. 7 ) ng/L) , BNP increased significantly in the RVA group at the 6th,12th and 24th month after operation( ( 108. 2 ±29. 8) , ( 190. 3 ±46. 7) ,(308. 2 ±56. 5)ng/L,respectively) (P <0. 05). In the RVS group,BNP increased only at 24 months after pacing ( (75. 2 ± 15. 8) ng/L vs. (63. 9 ± 15. 1 ) ng/L) (P < 0. 05). There was significant difference on BNP between the two groups. LVEDD,LVEDV increased,LVEF declined at 12 months after pacing in the RVA group,which were not observed in the RVS group. There was significant difference on LVEDD,LVEDV and LVEF in the RVA group (P< 0. 05) between the 12th month and pre-operation,and there were no significant difference in the RVS group (P > 0. 05). Conclusions Compared to RVA pacing,RVS pacing was more beneficial to improve heart function,prevent cardiac remodeling and decline the activation of nerve-endocrine.

Objective To study the clinical profile of patients with central nervous system (CNS) involvement in relapsing polychondritis (RP).Methods Clinical data of five patients of RP with CNS lesions were collected,and compared with those from the literatures.T test and Fisher exact test were used for statistical analysis.Results Among 205 patients with RP in Peking Union Medical College Hospital,five cases (2.4％) had CNS damage.All 5 cases presented an active onset and occurred in the active phase of RP.All of them manifested as meningoencephalitis,complicating cranial neuropathies in 2 cases (2/5).Cerebrospinalfluid examination revealed non-specific meningeal inflammation,and magnetic resonance image (MRI) showed long T2 signals in brain lesions.Four patients (4/5) showed good response to high-dose glucocorticosteroid plus immunosuppressive agent combined therapy.The average age of our patients was younger than those in the literatures [(44± 14),(58± 11) years,respectively; t=2.547,P＜0.05],while other clinical features was not significantly different between the two groups.Conclusion CNS involvement is a rare condition in RP patients,and usually occurrs in the early course of active RP.Meningoencephalitis/ meningitis is the major clinical manifestations.MRI and cerebrospinal fluid examination may help to confirm the diagnosis.Treatment with corticosteroid and immunosuppressant can result in favorable response.

Background Studies showed that activation of microglia-derived nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a key role in the neurodegenerative diseases and neural cell death in central nervous system.The effect of NADPH on cone degeneration have been determined in rd rats,its role in rod degeneration is relatively less studied.Objective This study was to study the expression of NADPH oxidase in the retinal degenerative process in rd mice and further explore its role in the photoreceptor degeneration.Methods rd Mice at postnatal day 8 (P8),P10,P12,P14,P16 and P18 were collected.The mice were sacrificed,and retinal sections,RNAs and proteins were prepared in above-mentioned time points.The expressions of the gp91 phox,a major subunit of NADPH oxidase,in transcript level and protein level in the retinas were semi-quantitatively detected by real-time PCR and Western blot respectively.Expression of gp91phox was localized in the rd retinas as ageing by immunohistochemstry,and the co-expression of gp91phox with CD11b,a specific marker of microglial cells,was assayed by immunofluorescent double labeling.The C57BL/6N mice were served as controls.The use and care of the animals complied with the Guideline of ARVO.Results Real-time PCR showed that gp91phox mRNA was not expressed in the retinas of C57BL/6N mice.Gp91phox mRNA was found to have less expressed in retinas of P8 rd mice.With aging,the expression level of gp91phox mRNA (gp91phox mRNA/β-actin) in rd mouse retinas was gradually increased with the highest level in P14 mice(1.136±0.370).A significant difference was seen in the gp91 phox mRNA expression among various groups of mice (F=17.81,P =0.00),and gp91phox mRNA expression was significantly elevated in P10,P12,P14,P16 and P18 rd mice compared with P8 rd mice(all at P＜0.05).The expression level of gp91phox protein (A value) in the retinas presented with a similar trend in the rd mice,with a significant difference among the various ages of rd mice and C57BL/6N mice (F =354.00,P＜0.01).The expression level of gp91 phox protein was increased in the rd mice in comparison with the C57BL/6N mice (all at P＜0.05).Immunochemistry revealed that the positive response cells for gp91phox increased in the inner layers of retinas in P10 rd mice and peaked in P14 mice.Immunofluorescent double labeling exhibited that gp91phox were seen to present a co-expression with CD11b,showing an orange fluorescence.Conclusions Expression of NADPH oxidase in the rctinas in the rd mice up-regulates and is parallels to the microglial activation and photoreceptor degeneration,suggesting that NADPH oxidase plays a role in the retinal dystrophy associated with microglial activation.

Objective To explore the changes of different brain regions of the human beings during completion of spatial working memory tasks under hyperthermia condition with functional magnetic yesonance.Methods Twenty-eight right-handed healthy young male volunteers were divided into control group and hyperthermia group randomly,and working memory task using block design was performed during behavioral test and fMRI scanning on both conditions.Activation intensity and location of different brain areas were compared in control and hyperthermia group.Results The activations of frontal,parietal,occipital and insular lobe were seen in both of the control group and the hyperthermia group.Right lateralization was shown in control group during spatial working memory (Li=0.05 1).While,in hyperthermia group the effect of the right lateralization significantly was enhanced (Li=0.103). Moreover,activation of bilateral middle frontal gyrus and right parietal lobe were significantly enhanced.Conclusion It is found for the first time that the hyperthermia could affect bilateral middle frontal gyrus and right parietal lobe,and enhance the effect of right lateralization in the spatial working memory task.

OBJECTIVETo investigate the changes in serum protease and cytokine in patients with silicosis, tuberculosis, and lung cancer.

METHODSSerum samples of patients with silicosis, tuberculosis, and lung cancer were collected. The variation trends of the expression of granzyme A, cathepsin G, apolipoprotein A, and interferon-β (IFN-β) were analyzed using enzyme-linked immunosorbent assay.

RESULTSThe concentration of apolipoprotein A of the silicosis group was 200 µg/ml, significantly higher than those of the tuberculosis and lung cancer groups (P < 0.05), and the lung cancer group had a significantly higher concentration of apolipoprotein A compared with the tuberculosis group (P < 0.05). The silicosis group had significantly higher expression of cathepsin G compared with the tuberculosis and lung cancer groups (P < 0.05), and the tuberculosis group and lung cancer group showed no significant difference in the concentration of cathepsin G (P > 0.05). The tuberculosis group had a significantly higher concentration of granzyme A than the silicosis and lung cancer groups (P < 0.05), and the silicosis group and lung cancer group had similar protein concentration trends (P > 0.05). The tuberculosis group and lung cancer group had significantly higher concentration of IFN-β compared with the silicosis group (P < 0.05), and the tuberculosis group and lung cancer group showed no significant difference in IFN-β concentration (P > 0.05).

CONCLUSIONThis study may offer diagnostic markers for the clinical diagnosis of silicosis, tuberculosis, and lung cancer, and could provide a basis for the research, as well as potential molecular targets for the diagnosis and treatment of these diseases.

Biomarkers ; Cathepsin G ; metabolism ; Cytokines ; blood ; Endopeptidases ; blood ; Enzyme-Linked Immunosorbent Assay ; Granzymes ; metabolism ; Humans ; Interferon-beta ; metabolism ; Lung Neoplasms ; enzymology ; Silicosis ; enzymology ; Tuberculosis ; enzymology

Objective To investigate the clinical features of IgG4-related autoimmune pancreatitis (IgG4-related AIP).Methods A prospective cohort study on IgG4 related disease (IgG4-RD) was carried out in Peking Union Medical College Hospital during December 2010 to June 2012,a total of 50 patients were recruited,including 14 IgG4-related AIP patients.The clinical manifestations,laboratory tests results,radiographic findings,histopatholo-gical lesions and response to treatment were analyzed.Results Fourteen AIP patients accounted for 28％ of IgG4-RD,of whom 9 cases were male,5 females,with the mean age of (55±10) (range 41-71) years.Painless obstructive jaundice was the major manifestation of AIP.All patients had extra-pancreatic organ involvement,including salivary glands enlargement (10 cases),lymph nodes swollen (7 cases),and bile duct tree (6 cases),lung (6 cases),kidney (2 cases),lacriminal gland (2 cases),retroperitoneal tissue (1 case),mesentery (1 case),and prostate (1 case) involvement.Serum levels of IgG4 subclass in all patients were significantly increased,with mean concentration of (11 ±10) (range 1.4-35.2) g/L.Radiographic findings showed diffuse (13 cases) or focal (1 case) pancreatic enlargement with irregular narrowing of the pancreatic duct (4 cases).Histopathological examinations were performed in 12 patients,which revealed massive infiltration with lymphocytes and IgG4 positive plasma cells with remarkable tissue fibrosis.Response to glucocorticosteroid or combined steroid and immunosuppressants were good.Conclusion IgG4-related AIP is a subtype of chronic pancreatitis,which is characterized by specific clinical spectrum,serological markers,radiographic and histopathological features.Glucocorticosteroid is the first choice,which can significantly improve the clinical and imaging abnormalities.

Objective To explore the occurring and developing characteristics of dry eye syndrome in type 1 diabetic mouse model induced with streptozotocin (STZ)-intraperitoneal injection.Methods Completely randomized design method was performed.Sixty SPF degree male C57BL/6 mice (6-8 weeks old) was randomly divided into diabetic group and control group,which were intraperitoneally injected with citrate buffer and STZ-citrate buffer (50 mg/kg per day),respectively.The average weight,blood glucose level and lacrimal gland weight were examined before injection and 1 month,2 months,4 months after the last injection;meanwhile,phenol cotton thread and rose bengal staining methods were used to check tear formation and ocular surface condition;corneal perception meter was used to test corneal sensitivity;periodic acid-schiff (PAS) staining method was used to test the density of conjunctival goblet cells;histopathological staining and Masson staining methods were used to test the tissue changes of lacrimal gland.Results Compared with before injections,the body weight and lacrimal gland weight in diabetic group were not significantly changed 1 month,2 months and 4 months after injection (all at P＞ 0.05),but these measurements in diabetic group 1 month,2 months and 4 months after injection were significantly lower than those in control group at corresponding time points (all at P＜0.05).Compared with before injections and control group at corresponding time points,the blood glucose level were dramatically higher and the tear formation were significantly decreased in diabetic group at 1 month,2 months,4 months after injection (all at P＜0.05).The ocular surface of diabetic model mice showed positive rose bengal staining 2 months after STZ injections.The corneal sensitivities were significantly lower in diabetic model mice 2 months and 4 months after injection than those before injection and in control group at corresponding time points (all at P＜0.05).The density of conjunctival goblet cells in diabetic group 4 months after injection was significantly decreased than those before injection in diabetic group and 4 months after injection in control group (all at P＜0.05).The apparent collagen fibrosis and inflammatory cell infiltration were observed at lacrimal gland in diabetic model mice 4 months after injection.Conclusions The major early stage manifestations of STZ induced type 1 diabetes mice include retarded growth of lacrimal gland and decreased tear secretion volume,which gradually develop along the course of diabetes;in the later stage,the manifestations include decreased corneal sensitivity,ocular structural damage,structural changes of lacrimal gland and decreased conjunctival goblet cell density.