[Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type].

Objective: To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL). Methods: A total of 557 patients from 2000-2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis. Results: The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 (P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population (P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy (P<0.001). Radiotherapy dose was an independent factor affecting LRC(P<0.05). Conclusions: Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

[Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract].

Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

[The effects of sequence of radiotherapy and chemotherapy on prognosis of patients with early-stage extranodal NK/T cell lymphoma (nasal type) and its individualized application].

Objective: To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early-stage extranodal NK/T-cell lymphoma (nasal type, ENKTCL) patients, and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy. Methods: The Chinese Lymphoma Collaborative Group (CLCG) collected the clinical data of 2 008 patients with early-stage Ⅰ/Ⅱ ENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country, including 1 417 males and 591 females, aged 2 to 83 (42±14) years. According to the sequence of radiotherapy and chemotherapy, patients were divided into radiotherapy-first group (388 cases) and chemotherapy-first group (1 620 cases). Survival rate was estimated using Kaplan-Meier method, and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors. The prognostic prediction models of the two therapies were constructed separately, and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient. Results: The 5-year overall survival rate was 74.2% (95%CI: 69.6%-79.2%) in the radiotherapy-first group and 69.7% (95%CI: 67.1%-72.4%) in the chemotherapy-first group. Although the 5-year overall survival rate of patients in the radiotherapy-first group was numerically higher than that of the chemotherapy-first group, the difference was not statistically significant (χ2= 2.26, HR=0.84 (95%CI: 0.68-1.05), P=0.133). Six variables including age, gender, ECOG score, LDH, Ann Arbor staging, and PTI (primary tumor invasion) were screened out as independent prognostic factors (the chemotherapy-first group: HR were 1.01, 1.25, 2.07, 0.77, 1.34, 1.49, respectively, all P<0.05; radiotherapy-first group: HR were 1.02, 1.31, 1.66, 0.78, 1.37, 1.29, all P>0.05). The mean 5-year predicted mortality risk for all patients receiving radiotherapy-first regimen was lower than those receiving chemotherapy-first regimen (26.8% vs 30.2%, P<0.001). There were individualized differences in the predicted mortality risk of patients with different clinical characteristics who received radiotherapy-first regimen or chemotherapy-first regimen. Conclusion: Patients with stage Ⅰ/Ⅱ ENKTCL treated with radiotherapy-first regimen had a better expected prognosis than patients treated with chemotherapy-first regimen. The quantitative assessment of the differential effects of the sequence of radiotherapy and chemotherapy on the mortality risk of individual patients based on their clinical characteristics was helpful for the clinical development of the optimal radiotherapy and chemotherapy plan for each patient.

[The cytotoxity of DOP on PC12 cells and it's effect on processing of APP-enzymolysis].

Objective: To study the toxicity of dioctyl phthalate (DOP) on adrenal pheochromocytoma (PC12) cells and its effect on processing of amyloid precursor protein (APP) -enzymolysis. Methods: In vitro experiments, PC12 cells were divided into blank control (CT) , low DOP (DOP1) , medium DOP (DOP2) , high DOP (DOP3) , low DOP+Aß(25-35) (DOP1+Aß) , medium DOP+Aß(25-35) (DOP2+Aß) , high DOP+Aß(25-35) (DOP3+Aß) , Aß(25-35) (Aß) , a total of 8 groups, each with 4 samples. The cell viability was measured by MTT assay, the contents of lactate dehydrogenase (LDH) , malondialdehyde (MDA) and nitric oxide (NO) were measured, and cysteine protease 3 (Caspase-3) was determined by Western blot. In the transfection experiment, the hamster ovary (CHO) cells were transfected with APP695 and treated with different concentrations of DOP. They were divided into V-Flag control (V-Flag) , APP695-Flag (APP695) , low DOP (DOP1+APP695) , medium DOP (DOP2+APP695) , high DOP (DOP3+APP695) , a total of 5 groups, each with 4 samples. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of Aß(1-40) and the activity of γ-secretase. In vivo experiment, 50 male Kunming mice of SPF grade, weighing (20±2) g, were selected and randomly divided into control, lead (Pb) , low DOP (DOP1＇) , medium DOP (DOP2＇) , high DOP (DOP3＇) consisted of 5 groups, each with 10 mice, continuously gavage for 6 weeks. Morris water maze method was used to detect the effect of different concentrations of DOP on learning and memory in mice, and ELISA method was used to detect ß-secretase, γ-secretase activity and Aß(1-40) content in brain tissue. Results: Compared with the CT group, the cell viabilities of the DOP2 and DOP3 groups were decreased, and the contents of LDH, MDA, and NO were increased, and the differences were statistically significant (P<0.05) . Compared with the CT group, the cell viabilities of DOP1+Aß, DOP2+Aß and DOP3+Aß groups were decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant (P<0.05) . Compared with the Aß group, the cell viability of DOP3+Aß group was decreased, the contents of LDH, MDA, NO were increased, the differences were statistically significant (P<0.05) . Compared with the Aß group, the contents of LDH and NO in the DOP2+Aß group were increased, and the differences were statistically significant (P<0.05) . Compared with the CT group, the expression levels of Caspase-3 in the DOP2 and DOP3 groups were increased, and the differences were statistically significant (P<0.05) . Compared with the Aß group, the expression levels of Caspase-3 in the DOP2+Aß and DOP3+Aß groups were increased, and the differences were statistically significant (P<0.05) . Compared with the APP695 group, the contents of Aß(1-40) and the activities of γ-secretase of the DOP2+APP695 and DOP3+APP695 groups were increased (P<0.05) . Compared with the control group, the activities of ß-secretase, γ-secretase and the content of Aß(1-40) in the brain tissue of DOP3＇group were increased, and the differences were statistically significant (P<0.05) . Compared with the Pb group, the activities of ß-secretase, γ-secretase and the content of Aß(1-40) of the DOP3＇group were increased, and the differences were statistically significant (P<0.05) . Compared with the control group, the target quadrant stay time and the number of crossings in the DOP2＇and DOP3＇groups were reduced, and the differences were statistically significant (P<0.05) . Conclusion: DOP has a certain toxic effect on PC12 cells, causing learning and memory impairment in mice, and may promote the pathological progression of Alzheimer＇s disease.

[Ultrastructural and clinical findings of mitochondrial encephalomyopathy:report of 27 cases].

Objective: To investigate the ultrastructural features of muscle in patients with mitochondrial encephalomyopathy for its diagnosis and differential diagnosis. Methods: The clinical data of 27 mitochondrial encephalomyopathy patients who underwent left or right biceps brachii muscle biopsy at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from July 2006 to August 2017 were analyzed retrospectively. The muscle biopsy specimens were examined underlight microscope and transmission electron microscope. Results: There were 27 patients (17 males, 10 females) with an age range of 12 to 62 years (mean 29 years). The age of onset ranged from 3 to 38 years. The course of disease ranged from 1 month to 24 years. Twenty-two cases presented with lactic acidosis and stroke-like episodes (MELAS) syndrome, four with myoclonic epilepsy with ragged red fibers (MERRF) syndrome, and one with chronic progressive paralysis of extraocular muscle (CPEO) syndrome. Skeletal muscle biopsy showed abundant ragged red fibers and strongly SDH-reactive vessel. Genetic studies showed 17 of 22 cases of MELAS syndrome had A3243G mutation, and the other 5 cases had no abnormality. A8344G mutation was found in 3 of 4 cases of MERRF syndrome. No single or multiple mtDNA mutations were found in the single case of CPEO. Transmission electron microscopy of all 27 cases showed diffuse proliferation of mitochondria between the myofibrils and beneath the sarcolemma, with increased spacing between muscle cells. Seven cases showed numerous glycogen and four showed subsarcolemmal lipid droplets, 13 cases showed unusual mitochondrial morphology, including mitochondrial electron-dense substances and paracrystal line inclusions ("parking lot" change)in eight cases. Conclusions: Transmission electron microscopy shows significant differences in ultrastructural pathological changes among different patients with mitochondrial encephalomyopathy. Some patients with mild clinical symptoms have increased mitochondrial number, increased metabolism of glycogen and lipid droplets, while others with severe clinical symptoms have abnormal mitochondrial morphology. Typical crystalloid inclusions are found in mitochondria, which are of great value in the diagnosis of this disease.

[Prevalence and risk factors of diabetic retinopathy in hospital patients].

Objective: To analyze the prevalence and risk factors of diabetic retinopathy (DR) in ophthalmic patients. Methods: A cross-sectional study was performed. Diabetic patients who were admitted to Department of Ophthalmology, Traditional Chinese Medicine Hospital of Muping between October 2012 and June 2013 were included. General information and medical history were obtained from each subject by questionaires. Laboratory and detailed ophthalmic examinations were performed during the study. DR was diagnosed and graded by mydriatic fundus photography. Prevalence of DR was calculated and logistic regression was used to analyze the relationship between DR and various factors. Results: A total of 676 diabetic patients were included, and 455 of them presented with DR at a morbidity rate of 67.31%. Among DR patients, the number of mild, moderate, severe non-proliferative diabetic retinopathy (NPDR) patients and proliferative diabetic retinopathy (PDR) patients were 211 (46.37%), 167 (36.70%), 57 (12.53%) and 20 (4.40%), respectively. There was no significant difference in the prevalence of DR among different age groups (χ(2)=6.527, P=0.089). However, there was a significant difference between different disease duration groups (χ(2)=39.401, P<0.001), as well as between insulin therapy group and non-insulin therapy group (χ(2)=7.378, P=0.007). The multivariate logistic regression analysis demonstrated the independent risk factors for DR occurrence were hemoglobin A1c (HbA1c) (OR=1.131, 95%CI: 1.022-1.252, P=0.011) and duration of diabetes (OR=1.077, 95%CI: 1.046-1.108, P<0.001). Conclusions: The prevalence of DR in ophthalmic patients was associated with duration of diabetes, HbA1c, obesity, smoke, nephropaty and insulin therapy. Increased HbA1c level and longer duration of diabetes were independent risk factors for DR in diabetic patients.

[The associations between comorbidity and exacerbation risk in patients with chronic obstructive pulmonary disease].

Objective: To study the association between comorbidity and acute exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). Methods: This was a prospective cohort study with 64 stable COPD patients included. There were 64 males and 18 females with an average age of (68±9) years. Clinical characteristics, the number and type of comorbidities were recorded, and Charlson comorbidity index (CCI) was calculated. The patients were interviewed by phone calls every 3 months since baseline in which the number of acute exacerbations was recorded until 12 months. The impact of CCI, the number of comorbidities and certain comorbidities in the prediction of COPD exacerbation risk were analyzed. Results: Compared to patients with a lower CCI score, patients with a higher CCI score were older (75±6 vs 62±8), and had more severe lung function impairment [FEV(1)%pred: (40±18)% vs (52±18)% ], higher number of comorbidities [4(3, 7) vs 1(1, 3)] and higher frequency of hospital admission due to acute exacerbation [1(0, 2) vs 0(0, 0.25)]. In comparison with patients with lower number of comorbidities, patients with higher number of comorbidities were older (72±7 vs 64±10), and had higher mMRC score [2(1, 3) vs 2(1, 2)] and more severe lung function impairment [FEV(1)%pred: (42±15)% vs (53±19)% ], higher age adjusted CCI score [5(3, 5) vs 3(2, 3) ] and more courses of systemic corticosteroids [2(0, 3) vs 0(0, 0.75)] and/or antibiotics use [3(2, 4) vs 1.5(1, 2.75)]. The number of hospitalizations and total number of exacerbations were higher in COPD patients with bronchiectasis than those without (P<0.005). Conclusion: The inclusion of clinically meaningful comorbidities into the combined assessment of COPD for the prediction of disease prognosis deserves further study.

Large Positive Thermal Expansion and Small Band Gap in Double-ReO3-Type Compound NaSbF6.

Double-ReO3-type structure compound NaSbF6 undergoes a low-temperature rhombohedral to high-temperature cubic phase between 303 and 323 K, as revealed by temperature-dependent X-ray diffractions. Although many double-ReO3-type fluorides exhibit either low thermal expansion or negative thermal expansion (NTE), NaSbF6 exhibits positive thermal expansion (PTE) with a large volumetric coefficient of thermal expansion, αv = 62 ppm/K, in its cubic phase. Raman spectroscopy reveals that the low-frequency transverse vibration of fluorine atoms is stiffened in NaSbF6, compared with the typical NTE compound CaZrF6 with the same structure. The related weak contraction associated with the polyhedral rocking would be overcome by the notable elongation of the Na-F bond length on heating, thus leading to the large volumetric PTE. Unlike ScF3 and CaZrF6 which are insulators with a wide band gap, a relative small band gap of 3.76 eV was observed in NaSbF6. The small band gap can be attributed to the hybridization between the Sb 5s and F 2p orbitals.

Radiotherapy effects on brain/bone metastatic adenocarcinoma lung cancer and the importance of EGFR mutation test.

This study proposed to retrospectively analyze the efficacy of radiotherapy on brain/bone metastases in patients with stage IV lung adenocarcinoma and to evaluate the correlation between overall survival after radiotherapy and other factors including metastatic sites and EGFR mutation status. 115 patients with Stage IV lung adenocarcinoma admitted to our center from March, 2011 to December, 2013 were enrolled. They presented with metastases to no other solid organs except the bone or brain and had received no prior treatment. 50 patients received EGFR mutation test with 32 detected as EGFR mutant and 18 wild-type. Patients with brain metastases were treated with 40 Gy whole brain irradiation (WBI) in 2 Gy fractions; patients with bone metastases were treated with 30 Gy local irradiation in 3 Gy fractions or 40 Gy in 2 Gy fractions. All the patients received systemic therapy during or after radiotherapy and 68 received targeted therapy.The median overall survival of patients with solitary brain metastases, solitary bone metastases or combined brain and bone metastases were 8.50 months, 8.50 months and 9.50 months respectively, revealing no significant difference (p=0.57). The median overall survival of patients with EGFR mutations was 10.25 months, longer than the 8.75 months of patients without EGFR mutations, revealing no significant difference (p=0.57). The median overall survival of EGFR mutant patients with solitary bone metastases, solitary brain metastases or combined brain and bone metastases were 7.50 months, 10.50 months and 11.50 months respectively, revealing no significant difference (p=0.91). 36 patients with untested EGFR mutation status received EGFR-TKI. Among EGFR mutant patients, 10 didn't receive targeted therapy; 8 were administered Erlotinib and 14 Gefitinib with median overall survival of 10.25 months and 14.5 months, showing no significant difference (p=0.11) between the two drugs. When patients with stage IV lung adenocarcinoma have been treated by early radiotherapy, the overall survival doesn't correlate with metastatic sites. Radiotherapy could extend survival for EGFR mutant patients with stage IV lung adenocarcinoma. EGFR mutation test should be performed before treatment of the disease.

Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15.

A transgenic cell line stably expressing the human organic anion transporting polypeptide (OATP1B1) was established. Human Embryonic Kidney 293 (HEK293) cell line stably expressing OATP1B1*1a sequence was amplified through PCR with the extracted total RNA as templates from human liver, then subcloned into the plasmid pMD19-T and verified by sequencing. OATP1B1*1b/OATP1B1*15 mutant sequences were obtained by site-directed mutation PCR with pMD19-T/ OATP1B1*1a as templates. The plasmids pcDNA3.1(+)/OATP1B1*1a, *1b and *15 were constructed and transfected into HEK293 cell line using Lipofectamine 2000 transfection reagent. Several stable transfected clones were obtained after selection with G418. Using rosuvastatin as a probe substrate of OATP1B1, the intracellular rosuvastatin accumulation in HEK293 and HEK-OATP1B1*1a, *1b and *15 monoclone cells were validated by a ultra-performance liquid chromatography-tandem mass spectrometry. OATP1B1 mRNA and protein expression were detected by RT-PCR and Western blot, respectively. The results from RT-PCR, rosuvastatin uptake and Western blot assay indicated that human OATP1B1 was highly expressed in transfected cells compared with controls. The HEK-293 cell lines stably expressing human OATP1B1-wild and variant (HEK-OATP1B1, *1b and *15) are potential models to study drug transport in vitro.

[Comparison of radiofrequency catheter ablation for paroxysmal supraventricular tachycardia guided by three dimensional navigation with X-ray].

Objective: To compare the therapeutic efficiency and safety of radiofrequency catheter ablation (RFCA) for paroxysmal ventricular tachycardia (PSVT) guided by three-dimensional navigation with X-ray. Methods: One hundred and seventy-six patients with PSVT hospitalized in Department of Cardiology, Zhejiang Provincial People's Hospital between January 2013 and December 2014 were enrolled in this study. RFCA was performed on 95 patients (Group A) guided by the three dimensional electric-field navigation system (NavX) and the procedures were done with the spatial localization method, unless X-ray was needed in some cases.Eighty-one patients (Group B) underwent RFCA guided by X-ray only.The success rate, complications, recurrence rate, operation time, and X-ray exposure were compared between the two groups. Results: The immediate success rate of operation was 100% in the 176 PSVT patients without complications.There were recurrences in 2 cases of Group A, while in 1 case of Group B. The average operation time in Group A was (97±20) min, while (91±26) min in Group B. The median X-ray fluoroscopy time was 3.0 min and radiation dose was 18.5 µGym2 in Group A, which were significantly reduced compared with those in Group B (34.5 min, 167.3 µGym2) (P<0.05). There was no significant difference in immediate procedure success rate, complications, recurrence, and operative time between this two groups (P>0.05). Conclusions: The RFCA for PSVT guided by three-dimensional navigation is safe and feasible in the experienced electrophysiological center.Most patients suffer less or no X-ray radiation.

[Inhibitory effect of migration-inducing gene-7-shRNA recombinant retrovirus combined with endostatin on growth and metastasis of hepatoma xenograft].

Objective: To investigate the inhibitory effect of migration-inducing gene-7(Mig-7)interfered with retrovirus-mediated RNA(shRNA)combined with recombinant human endostatin(ES)on the growth and metastasis of subcutaneous xenograft of human hepatoma cells in nude mice. Methods: Two Mig-7-mRNA oligonucleotide sequences(Mig-7-shRNA-1 and Mig-7-shRNA-2)and one sequence as a negative control(Mig-7-shRNA-N)were designed. The specific Mig-7-shRNA recombinant retrovirus expression vector plasmid was constructed and used for the transfection of human hepatoma MHCC-97H cells with high expression of Mig-7. The subcutaneous xenograft tumor model of human hepatocellular carcinoma(HCC)in nude mice was established, and according to the condition of transfection and administration, the nude mice were divided into pSIREN-M1 group, pSIREN-MN group, ES group, and pSIREN-M1+ES group. The xenograft tumor volume, mass, and metastasis were compared between groups. Immunohistochemistry was used to observe the formation of vasculogenic mimicry(VM)in xenograft tumor and the difference in tumor microvascular density(MVD), and Western blot was used to measure the expression of Mig-7 and vascular endothelial growth factor(VEGF)in each group. A one-way analysis of variance was used for comparison between groups, and the Fisher's exact test was used for comparison of continuous data between groups. Results: Compared with the pSIREN-MN group, the pSIREN-M1 group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, and formation of VM(P < 0.05), as well as significantly higher VEGF expression and MVD(P < 0.05). Compared with the pSIREN-MN group, the ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, VEGF expression, and MVD(P < 0.05), as well as significantly higher Mig-7 expression and formation of VM(P < 0.05). Compared with the pSIREN-M1 group and the ES group, the pSIREN-M1+ES group had significantly lower xenograft tumor volume, mass, and metastasis rate, Mig-7 expression, formation of VM, VEGF expression, and MVD(P < 0.05). Conclusion: Mig-7-shRNA recombinant retrovirus combined with ES has a better inhibitory effect on the growth and metastasis of HCC xenograft tumor than Mig-7-shRNA recombinant retrovirus or ES alone. The anti-tumor angiogenesis therapy alone, which targets vascular endothelial cells in vivo, has a limited effect, since it may promote the formation of VM.

Hypoxia-inducible factor-1α expression in the different stages of rat thromboangiitis obliterans.

We investigated the expression and effects of hypoxia-inducible factor-1α (HIF-1α) in rat thromboangiitis obliterans (TO). Rats were divided into sham and model groups. The model group was further divided into groups based on observation duration. Lauric acid was injected below an artery clamp to simulate TO in the model group; saline was used in the sham group. Clamps were removed 15 min after injection in both groups, and physiological changes were observed at different times (gross observation and hematoxylin and eosin staining). The animals were killed at various times following the operation and serum and muscle tissues were sampled. For the sham group: the endometrium was relatively intact; medial membrane and epineurium lesions were absent; and blood vessels and surrounding tissues had no inflammatory cell infiltration. For the model group: all subgroups displayed inflammation; large numbers of inflammatory cells were gathered; muscle tissue lost its normal texture and structure; and the internal elastic membrane was integrated. Compared with the preoperative status, HIF-1α expression increased significantly in all subgroups (P < 0.05); there was no change in the sham group. HIF-1α expression in each subgroup was different (F = 14.267, P < 0.05). Femoral artery injection of lauric acid can be used as a rat TO model owing to its simple application and success rate. HIF-1α expression increased in the early stage of TO and gradually decreased with the extension of ischemia time; it may play a leading role in TO development and can be used for diagnosis and cure evaluation.

Vulnerability of atherosclerotic plaques is associated with type I interferon in a murine model of lupus and atherosclerosis.

This study aimed to investigate the relationship between type I interferon (IFN-I) and plaque stability in pristane-treated apolipoprotein E-knockout (ApoE(-/-)) mice. Antinuclear antibody (ANA) and extractable nuclear antigen antibody (ENA) levels were measured by immunofluorescence and enzyme-linked immunospot assay. Atherosclerotic plaques were detected by Sirius red/fast green staining. Cell apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling. Gene expression was determined by real-time PCR analyses. We found that pristane-treated ApoE(-/-) mice developed a lupus-like syndrome characterized by an increased production of serum ANA and ENA. Pristane treatment decreased the collagen content and increased the number of apoptotic cells in plaques. Moreover, IFN-induced ISG15, IFIT1-1, and IFIT1-2 gene expression was increased in peripheral blood cells and aortic plaques. An IFN-α-stimulated macrophage supernatant inhibited collagen type I, alpha 1 gene expression in vascular smooth muscle cells. We concluded that the vulnerability of plaques was associated with the activation of IFN-I in pristane-treated ApoE(-/-) mice. Thus, we speculated that the higher prevalence of cardiovascular events in patients with systemic lupus erythematosus could be due to plaque instability.

Emission properties and CW laser operation of Pr:YLF in the 910 nm spectral range.

The polarized emission spectra for the 3P0→1G4 emission transition of the Pr3+ ion around 910 nm in the Pr3+:LiYF4 (Pr:YLF) laser crystal were registered and calibrated in unit of cross sections for the first time. Continuous-wave (CW) laser operation is demonstrated at 915 nm in π polarization by pumping the crystal with an optically pumped semiconductor laser (OPSL) at 479.2 nm. An output power of 218 mW is thus obtained with a laser slope efficiency of about 24% for an output coupler (OC) transmission of 1.9%. CW laser operation is also demonstrated at 907 nm in σ polarization by using a thin plate oriented at Brewster angle. An output power of about 89 mW with a slope efficiency of about 10% is then obtained for an OC transmission of 0.8%.The round-trip cavity losses are estimated for different experimental cavity configurations to be about 1% and the typical beam quality M2 factors measured in the transverse x and y directions are found equal to about 1.07 and 1.04, respectively. Finally, we also report on a double laser wavelength operation by using an OC with a transmission of about 0.05%, such effect resulting from joint-etalon effects inside the cavity.

The economic burden of fracture patients with osteoporosis in western China.

UNLABELLED: To study the cost of osteoporotic fracture in China, we performed a prospective study and compared the costs of the disease in referral patients with fractures in three of the most common sites. Our results indicated that the economic burden of osteoporotic fracture to both Chinese patients and the nation is heavy. INTRODUCTION: This paper aims to study the cost of osteoporotic fracture in China and thus to provide essential information about the burden of this disease to individuals and society. METHODS: This prospective observational data collection study assessed the cost related to hip, vertebral, and wrist fracture 1 year after the fracture based on a patient sample consisting of 938 men and women. Information was collected using patient records, registry sources, and patient interviews. Both direct medical, direct non-medical, and indirect non-medical costs were considered. RESULTS: The annual total costs were highest in hip fracture patients (renminbi, RMB 27,283 or USD 4,330, with confidence interval (RMB 25715, 28851)), followed by patients with vertebral fracture (RMB 21,474 or USD 3,409, with confidence interval (RMB 20082, 22866)) and wrist fracture (RMB 8,828 or USD 1,401, with confidence interval (RMB 7829, 9827)). The direct medical care costs averaged approximately RMB 17,007 per year per patient, of which inpatient costs, drugs, and investigations accounted for the majority of the costs. Nonmedical direct costs were much less compared to direct healthcare costs and averaged approximately RMB 1,846. CONCLUSION: These results indicate that the economic burden of osteoporotic fracture to both Chinese patients and China was heavy, and the proportion of the costs in China demonstrated many similar features and some significant differences compared to other countries.

Clinical features of macrophage activation syndrome in the adult northern Chinese population.

OBJECTIVE: Macrophage activation syndrome (MAS) is a relatively rare but potentially fatal complication of childhood rheumatic illnesses. We sought to provide insight for the timely recognition and diagnosis of MAS and efficacious disease management in adults with rheumatic diseases. METHODS: Clinical files for eight adult MAS patients treated at the Second Affiliated Hospital of Harbin Medical University were analyzed for clinical manifestations, laboratory investigations, therapeutic measurements and clinical outcomes. RESULTS: The study included male and female patients with ages ranging from 16 to 59 years old. All patients were diagnosed with underlying rheumatic diseases with five patients having adult-onset Still's disease (AOSD), two patients having systemic lupus erythematosus (SLE) and one patient having Sjögren's syndrome (SS). The interval from fever onset to MAS diagnosis varied from seven days to 40 days. The most common clinical presentations were prolonged high fever, respiratory symptoms and jaundice. No patients had symptoms involving the central nervous system (CNS). Laboratory findings showed peripheral cytopenias, elevated liver enzymes, elevated triglycerides, hypofibrinogenemia and bone marrow hemophagocytosis. Potential effective treatments for MAS include glucocorticoid plus immunoglobulin therapy, but delays in diagnosis and treatment may lead to a fatal disease course. CONCLUSION: MAS in adults may not be as rare as was once thought, although the clinical features of MAS in adults often differ from those seen in children. The MAS mortality in adults is far higher than that for children. A diagnosis of MAS should be considered when a patient with rheumatic disease presents with prolonged high fever, peripheral cytopenia and liver failure. Collection of bone marrow aspirates is critical for accurate diagnosis and MAS therapy should begin as early as possible.

Serum brain-derived neurotrophic factor levels in epilepsy.

BACKGROUND AND PURPOSE: To clarify the utility of serum brain-derived neurotrophic factor (BDNF) as a biomarker for epilepsy diagnosis and severity. METHODS: Serum BDNF levels in 135 consecutive people with epilepsy meeting our criteria were assessed. Controls were 34 healthy individuals who over 12 months or longer had no complaints or signs of a neurological disorder. Serum BDNF concentrations were measured using Luminex technology. RESULTS: Gender, but not age, was found to be a significant factor related to serum BDNF levels in controls and people with epilepsy. Serum BDNF levels in people with epilepsy (mean 8798.5, SE 321.5 pg/ml) were not different from those of controls (mean 8919.5, SE 709.0 pg/ml). A multiple linear regression analysis, however, suggests that seizure frequency (P < 0.001) and epilepsy duration (P = 0.025) negatively correlate with serum BDNF levels independently of other factors. When BDNF cut-off values of 6260 pg/ml were used, the sensitivity for distinguishing people with daily or more frequent seizures from those with fewer seizures was 80% and specificity was 90%. CONCLUSIONS: It seems that the concentration of BDNF in serum is associated with disease severity in people with epilepsy and may be a helpful marker for severity.

Effect of radiotherapy on the treatment of patients with extensive stage small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive disease, in which more than 80% of patients present distant metastases at the time of first diagnosis. Chemotherapy is considered as the main treatment of extensive disease of SCLC (ED-SCLC), while the role of radiotherapy in the treatment of ED-SCLC is controversial. A case-control study was undertaken of patients diagnosed as ED-SCLC between 2004 and 2010. Fifty-eight patients with overall survival (OS) over 1 year were chosen, and another 58 patients with OS less than 1 year were selected as the control group, with the age, gender, metastasis or no metastasis of the liver, and the response after the first line of chemotherapy matched. The 1-year, 2-year, 3-year, and median OS of the 75 ED-SCLC patients who received radiation were 81.47, 29.89, 22.77%, and 17 months, respectively, and were 61.18, 23.53, 0%, and 16 months, respectively, for patients who did not receive radiation. The χ(2) test and odds ratio (OR) estimate demonstrated that these differences were statistically significant (χ(2) = 6.38, P = 0.0116; OR = 2.74, 95% confidence interval = 1.24-6.05). These results show that radiotherapy also plays a role in responding patients with extensive stage of SCLC.

Changes in the PD-1 and PD-L1 expressions of splenic dendritic cells in multiple-organ dysfunction syndrome mice and their significance.

The aim of this study was to evaluate the expression of surface molecules in splenic dendritic cells (DC) in multiple-organ dysfunction syndrome (MODS) mice and their effects on the immunosuppression of sepsis and MODS. One hundred thirty C57BL/6 mice were divided into 7 groups: 6, 12, 24, 48 h, 5-7 days, 10-12 days, and the normal control group. The sepsis-MODS mouse model was established by zymson injection into the peritoneal cavity. Histopathological changes in the spleen were evaluated by hematoxylin and eosin (HE) staining. After enrichment with BDTM IMag, the expressions of PD-1, PD-L1, MHC-II (I-A(b)), and CD86 in splenic DCs were examined by flow cytometry, and their relationship with sepsis development and MODS was analyzed. The histological structures of the spleen were damaged in the 24-, 48-h, and 10-12-day groups. PD-L1 expression increased 6 h after zymosan injection, decreased to normal levels at 24 and 48 h, and increased at 5-7 days, peaking at 10-12 days. The change in PD-1 expression roughly paralleled that of PD-L1. MHC-II and CD86 increased at 6 and 12 h, and dropped to normal levels at 10-12 days. In the early stage of injury, splenic DCs were mainly activated, whereas in the later stage, the expressions of the negative co-stimulatory molecules, PD-L1 and PD- 1, were upregulated, similar to tolerogenic DCs. Splenic DCs might suppress the stimulation of T lymphocytes in MODS mice through the PD-L1/PD-1 pathway, which would induce immunosuppression and the pathogenesis of MODS.