[Clinicopathological features of Helicobacter pylori-negative early gastric cancer].

OBJECTIVE: To investigate the clinicopathological features of Helicobacter pylori (Hp)-negative early gastric cancer. METHODS: The clinicopathological data of 30 cases of Hp-negative early gastric cancer were collected retrospectively at Pingdingshan Medical District, 989 Hospital of PLA Joint Logistics Support Force, and Beijing Chaoyang Hospital, Capital Medical University, from 2009 to 2021, and the histomorphological characteristics and immunophenotype were observed, and combined with the literature to explore. RESULTS: The median age of 30 patients was 58.5 years (range: 21-80 years), including 13 males and 17 females. The upper part of the stomach was 13 cases, the middle part of the sto-mach was 9 cases, and the lower part of the stomach was 8 cases. The median diameter of the tumor was 11 mm (range: 1-30 mm). According to the Paris classification, 9 cases were 0-Ⅱa, 7 cases were 0-Ⅱb, and 14 cases were 0-Ⅱc. Endoscopic examination showed that 18 cases of lesions were red, 12 cases of lesions were faded or white, and microvascular structures and microsurface structures were abnormal. In all the cases, collecting venules were regularly arranged in the gastric body and corner mucosa. There were 18 cases of well differentiated adenocarcinoma in the mucosa. The tumor presented glandular tubular-like and papillary structure, with dense glands and disordered arrangement; the cells were cuboidal or columnar, with increased nuclear chromatin and loss of nuclear polarity, and most of them expressed gastric mucin. Signet-ring cell carcinoma was found in 7 cases, all the cancer tissues were composed of signet-ring cells, and the cancer cells were mainly distributed in the middle layer to the surface layer of mucosa. Gastric oxyntic gland adenoma (gastric adenocarcinoma of the fundic gland type confined to mucosa) in 2 cases, gastric adenocarcinoma of the fundic gland type in 2 cases, and gastric adenocarcinoma of fundic gland mucosa type in 1 case. The tumor tissue was composed of branching tubular glands, except 1 case of mucosal surface epithelium was partially neoplastic, the other 4 cases of mucosal surface epi-thelium were all non-neoplastic; the cells were arranged in a single layer, and the nucleus was close to the basal side, and the nucleus was only slightly atypical. Pepsinogen I and H+/K+ ATPase were positive in 5 cases of gastric fundus gland type tumors, and 1 case of foveolar-type tumor cells at the surface and depth of mucosa showed MUC5AC positive. The gastric mucosa adjacent to cancer was generally normal in all cases, without atrophy, intestinal metaplasia and Hp. CONCLUSION: Hp-negative early gastric cancer is a heterogeneous disease group with various histological types, and tubular adenocarcinoma and signet-ring cell carcinoma are common. Tubular adenocarcinoma mostly occurs in the elderly and the upper to middle part of the stomach, while signet-ring cell carcinoma mostly occurs in young and middle-aged people and the lower part of the stomach. Gastric neoplasm of the fundic gland type is relatively rare.

[Clinicopathological features of verrucous type dysplasia of esophagus].

Objective: To investigate the clinicopathological features of verrucous type (squamous) dysplasia of esophagus. Methods: The clinicopathological data of 18 verrucous type dysplasia of esophagus patients in the 989th Hospital of the Joint Logistics Support Force of the People's Liberation Army (formerly 152 Central Hospital) and Beijing Chaoyang Hospital Affiliated to Capital Medical University from 2009 to 2021 were retrospectively collected. The histomorphologic characteristics and immunophenotype were observed, and human papillomavirus (HPV) genotyping was detected by PCR-fluorescence probe. The relevant literature was reviewed. Results: The median age of the 18 patients was 68 years (range 53-76 years); there were 13 males and 5 females. There were four cases in the upper esophagus, seven in the middle esophagus and seven in the lower esophagus. The median diameter of the lesion was 18 mm (range 6-54 mm). According to the Paris Classification, 11 cases were 0-Ⅱa, one case was 0-Ⅱa+Ⅰ, five cases were 0-Ⅱb, and one case was 0-Ⅱb+Ⅰ. White light endoscopy showed that the surface of the lesion was white plaque, red areas between the plaques, and papillary surface structure could be seen. In narrow-band imaging, some mucosal areas of lesions were opaque or patchy and light brown, and papillary microsurface structures were different in shapes and sizes. Intraepithelial microvessels were elongated, dilated, twisted and varied in diameter. Lugol iodine stain showed nil to faint staining. Histologically, the atypia cells were large with rounded to irregular nuclei, coarse chromatin, mitotic figures, and abundant eosinophilic cytoplasm. The basal cells showed increased atypia, crowding, increased nuclear-cytoplasmic ratio, and active mitosis. The cells were arranged haphazardly. Single cell keratinization, binuclear cells, and hollow-out-like cells, as well as surface epithelial keratinization and parakeratosis were observed in three cases. There were obvious verrucous or papillary structures in the epithelial layer. Five patients had local verrucous carcinoma. Immunohistochemical staining showed that the mutant expression of p53 protein in 6/10 cases; p16 was positive in 5/10 cases; abnormal Ki-67 distribution pattern in 10/10 cases. HPV was negative in all 10 cases tested. The original pathologic diagnosis of preoperative biopsy was high-grade dysplasia in 8 cases, low-grade dysplasia in 6 cases and atypical squamous epithelial cells in 4 cases. Conclusions: Esophageal verrucous dysplasia tumor cells are well differentiated with obvious verrucous or papillary structures. The unique morphological features suggest that it represents a histological subtype of esophageal squamous high-grade dysplasia and it is a precursor of verrucous carcinoma. Its preoperative biopsy diagnosis is challenging.

[Changes of cytokines in the aqueous humor of neovascular glaucoma at the angle-closure stage].

Objective: To evaluate the concentration of cytokines in the aqueous humor of neovascular glaucoma (NVG) patients at the angle-closure stage in different treatment periods and its relationship with recurrence. Methods: A prospective case-control study. Angle-closure stage NVG patients who came to Peking University Third Hospital from September 2018 to September 2019 were enrolled and followed-up for at least 12 months. Patients received triple sequential therapy, including anti-vascular endothelium growth factor (VEGF) injection, trabeculectomy, and panretinal photocoagulation. The aqueous humor before anti-VEGF treatment, before trabeculectomy, and during recurrence was collected. Multiplex bead immunoassay was applied to measure the concentration of 45 cytokines including VEGF, interleukin (IL), and chemokine. The relevant data were compared with the values of 25 proliferative diabetic retinopathy (PDR) patients and 24 age-related cataract patients undergoing phacoemulsification as controls. The concentration of cytokines was presented as M (Q1, Q3). The nonparametric Kruskal-Wallis H test was applied to compare the cytokine concentration between the NVG group and controls. The difference between the recurrence and non-recurrence groups was compared with the Mann-Whitney U test. Results: The average age of NVG patients was (60±11) years, and there were 22 males and 10 females. No significant differences were found in age and gender between the NVG group and the two control groups (both P>0.05). The median concentrations of VEGF in the NVG group before anti-VEGF treatment, before trabeculectomy, and after recurrence were 2 151.3 (1 433.1, 4 280.0) ng/L, 655.4 (287.3, 836.3) ng/L and 2 003.4 (1 603.1, 2 468.9) ng/L respectively. The concentrations of VEGF before anti-VEGF treatment and after recurrence in the NVG group were significantly higher than the PDR group [453.8 (189.9, 595.8) ng/L] and the cataract group [143.5 (112.7, 269.8) ng/L] (all P<0.05). The median concentration of programmed cell death protein ligand 1 (PD-L1) was 38.9 (22.4, 50.6) ng/L before anti-VEGF treatment, higher than that in the PDR group [12.0 (6.3, 20.1) ng/L] and the cataract group [14.6 (11.4, 19.3) ng/L]. The median concentration of fractalkine was 242.7 (189.0, 306.7) ng/L, higher than that in the PDR group [131.1 (119.1, 157.6) ng/L] and the cataract group [116.7 (10.2, 135.9) ng/L]. The median concentration of IL-7 was 18.0 (12.0, 32.7) ng/L, higher than that in the PDR group [7.7 (2.0, 10.8) ng/L] and the cataract group [3.3 (1.9, 6.8) ng/L]. The median concentration of eotaxin was 84.0 (52.4, 122.7) ng/L, higher than that in the PDR group [26.6 (17.1, 72.3) ng/L] and the cataract group [7.1 (5.6, 14.8) ng/L]. The median concentration of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was 3.6 (2.8, 6.4) ng/L, higher than that in the cataract group [1.1 (0.3, 2.3) ng/L]. All the differences were statistically significant (all P<0.05). There were no significant differences between the NVG and control groups in other cytokines or other treatment periods (all P>0.05). Six NVG patients suffered recurrence during the follow-up. The baseline concentration of IL-7 of these patients [10.5 (8.4, 16.0) ng/L] was significantly lower than that in patients who did not have recurred disease [22.7 (15.7, 34.1) ng/L] (Z=-2.74, P<0.01). Conclusions: In the angle-closure stage of NVG patients, the concentrations of VEGF, PD-L1, fractalkine, IL-7, eotaxin, and TRAIL in the aqueous humor significantly increase during the onset of disease. Lower IL-7 may indicate a recurring tendency.

[Pathological characteristics of colorectal adenoma with submucosal pseudoinvasion].

Objective: To investigate the pathomorphological characteristics of colorectal adenoma with submucosal pseudoinvasion and to summarize the corresponding pseudoinvasion patterns. Methods: The clinicopathological data of 9 cases of colorectal adenoma were collected at 989 Hospital of PLA Joint Logistics Support Force (4 cases) and Beijing Chaoyang Hospital, Capital Medical University (5 cases), from 2016 to 2019. retrospectively, and the histomorphological characteristics and immunophenotypes were analyzed, and discussed in light of the relevant literature. Results: There were 8 cases of adenoma with stalk. Tumor glands were found in the submucosa at the head end of adenoma, similar to infiltrating adenocarcinoma. The structure and cellular morphology of submucosal glands were very similar to the intramucosal tumor while the local submucosal tumor showed continuity with the intramucosal tumor. The submucosal tumors were lobule-like or nest-like with clear boundary. The outline of the gland was smooth and blunt-round, and there was loose fibromyxoid stroma around the gland, similar to the mucosa propria stroma. Some cases of the submucosal glands were cystic dilated with mucocele formation and hemosiderin deposition. One case with broad stalk-base showed an elevated adenoma with local high grade dysplasia involved in the aggregated lymphoid nodule, forming the lymphoglandular complexes, simulating invasive adenocarcinoma with associated submucosal lymphoid aggregates. Submucosal cancer tissue and intramucosal cancer tissue had continuity, and their morphology was the same. The submucosal tumor was round in the outline, smooth and blunt in the edge, and surrounded by lymphoid tissue. There was no stromal response around the gland to promote the proliferation of connective tissue, neither was there single-cell or small-cell cluster, sharp angle branch of gland, or vascular infiltration. Conclusions: There are two unique morphological patterns in colorectal adenoma with submucosal pseudoinvasion. Morphologically, the data show that one is lobular-like pattern, and the other is lymphoglandular complexes-like pattern. The main features of the two patterns are the same-morphology and continuity of submucosal tumor and intramucosal tumor. The pushed glands were surrounded by the intrinsic membrane stroma and muscularis mucosae in proper order, lacking the typical morphological characteristics of invasive adenocarcinoma.

[The value of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in evaluating the stability of atherosclerotic plaques].

Objective: Positron emission tomography-computed tomography (PET-CT) has been used to quantify inflammatory response in the body. The aim of the present study was to explore the possibility of using this method to evaluate the stability of atherosclerotic plaques and the efficacy of atorvastatin in stabilizing atherosclerotic plaques. Methods: Twenty New Zealand male white rabbits were included and divided into the atorvastatin intervention group and the control group, with 10 rabbits in each group. Rabbits in both groups were fed with a high fat diet for 20 weeks, and treated with thoracoabdominal aortic balloon-pulling to establish atherosclerosis model at the end of the 2nd week. Rabbits in atorvastatin intervention group was given atorvastatin intragastrically once a day. At the 8th week, thoracoabdominal aortic ultrasound was used to detect plaques in all rabbits. Blood was drawn at the 3rd and the 20th week, respectively, to measure blood lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). At the end of experiment, survival animals were scanned by (18)F-FDG PET-CT, and the average and maximum standard uptake values (SUVmean, SUVmax) of aortic segments were measured. Thereafter, the animals were sacrificed and aortic specimens of rabbits were taken and examined by immunohistochemistry. The pathological indexes were measured and compared. Results: At the end of experiment, the total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), hs-CRP [ (4.58±0.51) ng/ml vs.(5.87±0.66) ng/ml, P<0.01], MMP-9[ (43.93±2.16) ng/ml vs. (50.77±2.32) ng/ml, P<0.01], SUVmean (0.59±0.15 vs. 0.68±0.20, P<0.05) , SUVmax (0.68±0.20 vs. 0.81±0.27, P<0.05) , plaque area [ (0.36±0.24) mm(2) vs. (0.50±0.34) mm(2), P<0.05) ] and density of macrophage[ (4.34±1.54) % vs. (5.65±1.89) %, P<0.01] in the atorvastatin intervention group were significantly lower than those in the control group. In contrast, fiber cap thickness of the plaque[ (4.12±0.66) µm vs. (2.96±0.37) µm, P<0.01] in the atorvastatin intervention group was higher than that of the control group, and the difference was statistically significant. The arterial plaque areas were positively correlated with SUVmean (r=0.27, P<0.05) and SUVmax (r=0.43, P<0.01) . Fiber cap thickness was negatively correlated with SUVmean (r=-0.38, P<0.05) and SUVmax (r=-0.47, P<0.01) . The density of macrophage were positively correlated with SUVmean (r=0.52, P<0.01) and SUVmax (r=0.51, P<0.01) . Conclusion: (18)F-FDG PET/CT can be used to evaluate the efficacy of atorvastatin by the stability of atherosclerotic plaques.

Clinical and radiologic results after open-wedge high tibial osteotomy in haemophilic knee arthropathy with varus deformity.

INTRODUCTION: The previous studies have described only closed-wedge high tibial osteotomy (HTO) in haemophilic arthropathy (HA). AIM: The purpose of this study was to evaluate clinical and radiographic results after open-wedge HTO in HA with varus knee deformity. METHODS: We included 13 open-wedge HTOs in HA performed between 2005 and 2016. The mean age of patients was 28.9 years. Visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC), and range of motion (ROM) indices were assessed. Any complications or requirements for total knee arthroplasty (TKA) were investigated. Mechanical axis (MA), minimal joint space width (mJSW) and Pettersson score were measured. Bone union rates at 3 and 6 months postoperative were evaluated. RESULTS: VAS improved from 5.1 to 2.4 (P < .001). WOMAC was 66.5 preoperatively, and 26.6 postoperatively (P < .001). Pre- and postoperative ROM did not differ significantly. There were no cases of HTO converted to TKA, but one case of HTO required TKA 152 months postoperative. No complications were observed. The MA was corrected from varus 5.1° to valgus 1.2° (P < .001). Pre- and postoperative mJSW did not significantly differ. Pettersson score improved from 3.84 to 2.47 (P < .001). The bone union rates at the osteotomy gap were 45.2% and 67.8% at 3 and 6 months postoperative. CONCLUSIONS: Open-wedge HTO should be considered in cases of HA with varus deformity in young haemophilic patients, even though inflammatory arthritis is not an optimal indication for this procedure. It can be an appropriate treatment with respect to the choice to postpone TKA.

[Relationship between vertebral CT values and bone mineral density in patients with chronic obstructive pulmonary disease].

Objective: To explore a simple method for early detection of osteoporosis in patients with chronic obstructive pulmonary disease (COPD), by analyzing the correlation between computed tomography (CT) values of the thoracolumbar vertebrae and dual energy X ray absorptiometry (DXA). Methods: 86 patients with acute exacerbation of COPD were included in this study. The average age of the patients, including 57 males and 29 females, was 74±10 years. They all received chest CT and DXA examination within 1 month after admission. The relation between each CT value from 6(th) thoracic vertebrae (T6) to 1(st) lumbar (L1) and T-score measured by DXA was analyzed by linear correlation analysis with SPSS 17.0 software. Results: The mean CT value of T6-L1 was significantly lower in patients with osteoporosis than that in patients with normal bone mineral density (P<0.05). The CT values of T6-L1 were positively correlated with T-score (P<0.001). The ROC curve analysis of T6-L1 CT value showed that the area under ROC curve of L1 CT value was the largest, and therefore the accuracy of diagnosis of osteoporosis by L1 CT value was better.A L1 CT value lower than 100 HU was proposed as the threshold for lower bone mass or osteoporosis in the patients. Conclusion: It is possible to detect osteoporosis in patients with COPD through evaluating the CT values of T6-L1. This method could potentially reduce X-ray irradiation and expense. Early detection and intervention in patients with COPD and osteoporosis could improve the prognosis of patients.

Mid-term outcomes and complications of total knee arthroplasty in haemophilic arthropathy: A review of consecutive 131 knees between 2006 and 2015 in a single institute.

INTRODUCTION: Although total knee arthroplasty (TKA) in haemophilic arthropathy can reduce severe joint pain and improve functional disability, it is technically demanding. AIM: To evaluate mid-term outcomes and complications of TKA in haemophilic arthropathy. METHODS: This study retrospectively reviewed 131 consecutive primary TKAs in a single institute. The mean age was 41.0 years old, and the mean follow-up period was 6.8 years. Clinical and radiographic results were evaluated. Complications were categorized according to the classification system of the Knee Society for TKA complications. RESULTS: The average Western Ontario and McMaster Universities Arthritis Index (WOMAC) score improved from 66.0 to 24.2. The average flexion contracture significantly decreased from 17.3° to 4.7°, but the average pre- and postoperative maximum flexion did not differ (80.9° vs 85.6°, respectively). The average mechanical axis was varus 5.2° preoperatively and valgus 0.3° postoperatively. The coronal positions of the femoral and tibial components and the sagittal positions of these components were within ±3° in 83.2%, 89.3%, 63.4% and 73.3% of cases, respectively. Complications occurred in 17 knees (13.0%): hemarthrosis (n = 7), medial collateral ligament injury (n = 1), stiffness (n = 2), deep periprosthetic joint infection (PJI) (n = 3) and periprosthetic fracture (n = 4). CONCLUSIONS: The mid-term results of TKA in haemophilic arthropathy were satisfactory in pain relief, improved function and decreased flexion contracture. Bleeding and PJI continue to be major concerns for TKA in haemophilic arthropathy, and risk of periprosthetic fracture must be taken into account for patient education and appropriate prevention.

Comparison of mode of failure between primary and revision total knee arthroplasties.

INTRODUCTION: Cognizance of common reasons for failure in primary and revision TKA, together with their time course, facilitates prevention. However, there have been few reports specifically comparing modes of failure for primary vs. revision TKA using a single prosthesis. The goal of the study was to compare the survival rates, modes of failure, and time periods associated with each mode of failure, of primary vs. revision TKA. HYPOTHESIS: The survival rates, modes of failure, time period for each mode of failure, and risk factors would differ between primary and revision TKA. MATERIAL AND METHODS: Data from a consecutive cohort comprising 1606 knees (1174 patients) of primary TKA patients, and 258 knees (224 patients) of revision TKA patients, in all of whom surgery involved a P.F.C® prosthesis (Depuy, Johnson & Johnson, Warsaw, IN), was retrospectively reviewed. The mean follow-up periods of primary and revision TKAs were 9.2 and 9.8 years, respectively. RESULTS: The average 10- and 15-year survival rates for primary TKA were 96.7% (CI 95%,±0.7%) and 85.4% (CI 95%,±2.0%), and for revision TKA 91.4% (CI 95%,±2.5%) and 80.5% (CI 95%,±4.5%). Common modes of failure included polyethylene wear, loosening, and infection. The most common mode of failure was polyethylene wear in primary TKA, and infection in revision TKA. The mean periods (i.e., latencies) of polyethylene wear and loosening did not differ between primary and revision TKAs, but the mean period of infection was significantly longer for revision TKA (1.2 vs. 4.8 years, P=0.003). DISCUSSION: Survival rates decreased with time, particularly more than 10 years post-surgery, for both primary and revision TKAs. Continuous efforts are required to prevent and detect the various modes of failure during long-term follow-up. Greater attention is necessary to detect late infection-induced failure following revision TKA. LEVEL OF EVIDENCE: Case-control study, Level III.

Pre-operative features of non-invasive follicular thyroid neoplasms with papillary-like nuclear features: An analysis of their cytological, Gene Expression Classifier and sonographic findings.

OBJECTIVE: To investigate the corresponding cytological diagnoses, Gene Expression Classifier (GEC) results and ultrasound features of thyroid nodules diagnosed as non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), as well as any coexisting pathology. METHODS: We performed a retrospective review of thyroid nodules histologically diagnosed as NIFTP at our institution between 1st April 2016 and 1st April 2017. The following data points were collected: demographics, nodule size, ultrasound features, cytological diagnosis, GEC results, origin of sample (in-house vs outside hospital) and any additional pathology identified in the resection specimen. RESULTS: The case cohort included 87 nodules diagnosed as NIFTP (size range: 1-7 cm, mean: 2.5 cm) from 82 patients (age range: 22-82, mean age: 50.4, M:F-1:4.1). Corresponding FNA results were available for 72 nodules (82.8%) and were categorised as follows: benign (n = 5, 6.9%), atypia of unknown significance/follicular lesion of undetermined significance (n = 29, 40.3%), follicular neoplasm/suspicious for follicular neoplasm/follicular neoplasm with oncocytic features (n = 27, 37.5%), suspicious for papillary thyroid carcinoma (n = 6, 8.3%) and malignant (n = 5, 6.9%). GEC results were available for 32 (44.4%) nodules, with the majority of cases classified as suspicious (81.3%). On ultrasound, most of the nodules were predominantly solid (81.8%), vascular (93.8%), non-calcified (86.5%), and either hypoechoic (44.9%) or isoechoic (38.8%). In addition to NIFTP and other benign findings in the background thyroid, 75 separate malignant tumours were identified in 38 (46.3%) patients, many of which were papillary thyroid microcarcinomas (86.5%) with lymph node metastases present in two cases. CONCLUSIONS: The majority of thyroid nodules histologically diagnosed as NIFTP have indeterminate cytology (77.8%) and are classified as suspicious (81.3%) by GEC testing. Taken together, these findings can guide clinicians toward a more conservative therapeutic approach.

Infrared probe of pseudogap in electron-doped Sr2IrO4.

We report on infrared spectroscopy experiments on the electronic response in (Sr1-x La x )2IrO4 (x = 0, 0.021, and 0.067). Our data show that electron doping induced by La substitution leads to an insulator-to-metal transition. The evolution of the electronic structure across the transition reveals the robustness of the strong electronic correlations against the electron doping. The conductivity data of the metallic compound show the signature of the pseudogap that bears close similarity to the analogous studies of the pseudogap in the underdoped cuprates. While the low energy conductivity of the metallic compound is barely frequency dependent, the formation of the pseudogap is revealed by the gradual suppression of the featureless conductivity below a threshold frequency of about 17 meV. The threshold structure develops below about 100 K which is in the vicinity of the onset of the short-range antiferromagnetic order. Our results demonstrate that the electronic correlations play a crucial role in the anomalous charge dynamics in the (Sr1-x La x )2IrO4 system.

Infrared Spectroscopic Evidences of Strong Electronic Correlations in (Sr1-xLax)3Ir2O7.

We report on infrared spectroscopic studies of the electronic response of the (Sr1-xLax)3Ir2O7 system. Our experiments revealed hallmarks of strong electronic correlations in the evolution of the electronic response across the filling-controlled insulator-metal transition. We observed a collapse of the Jeff = 1/2 Mott gap accompanying the transfer of the spectral weight from the high-energy region to the gap region with electron doping. The intraband conductivity at the metallic side of the transition was found to consist of coherent Drude-like and incoherent responses. The sum rule and the extended Drude model analyses further indicated a large mass enhancement. Our results demonstrate a critical role of the electronic correlations in the charge dynamics of the (Sr1-xLax)3Ir2O7 system.

Projecting boreal bird responses to climate change: the signal exceeds the noise.

For climate change projections to be useful, the magnitude of change must be understood relative to the magnitude of uncertainty in model predictions. We quantified the signal-to-noise ratio in projected distributional responses of boreal birds to climate change, and compared sources of uncertainty. Boosted regression tree models of abundance were generated for 80 boreal-breeding bird species using a comprehensive data set of standardized avian point counts (349,629 surveys at 122,202 unique locations) and 4-km climate, land use, and topographic data. For projected changes in abundance, we calculated signal-to-noise ratios and examined variance components related to choice of global climate model (GCM) and two sources of species distribution model (SDM) uncertainty: sampling error and variable selection. We also evaluated spatial, temporal, and interspecific variation in these sources of uncertainty. The mean signal-to-noise ratio across species increased over time to 2.87 by the end of the 21st century, with the signal greater than the noise for 88% of species. Across species, climate change represented the largest component (0.44) of variance in projected abundance change. Among sources of uncertainty evaluated, choice of GCM (mean variance component = 0.17) was most important for 66% of species, sampling error (mean= 0.12) for 29% of species, and variable selection (mean =0.05) for 5% of species. Increasing the number of GCMs from four to 19 had minor effects on these results. The range of projected changes and uncertainty characteristics across species differed markedly, reinforcing the individuality of species' responses to climate change and the challenges of one-size-fits-all approaches to climate change adaptation. We discuss the usefulness of different conservation approaches depending on the strength of the climate change signal relative to the noise, as well as the dominant source of prediction uncertainty.

Regulatory T cells in the pathogenesis of type 2 diabetes mellitus retinopathy by miR-155.

OBJECTIVE: To explore the regulatory T cells (Treg) in the peripheral blood of diabetic retinopathy patients by microRNA-155 (miR-155), and investigate the mechanisms of regulatory T cells and miR-155 in the pathogenesis of diabetic retinopathy. PATIENTS AND METHODS: The study explores the percentage of CD4+ CD25+ Foxp3+ T cells (Treg cells) and the expression of miR-155 in the peripheral blood of 20 cases with background diabetic retinopathy (BDR group) and 20 cases with proliferative diabetic retinopathy (PDR group). Flow cytometry and RT-PCR determined 18 cases with non-diabetic retinopathy (NDR group) and 20 cases of healthy control (NC group). ELISA determined the expression of TGF-ß. RESULTS: The percentages of Treg cells in the peripheral blood of patients in BDR group, PDR group, and NDR group had significantly decreased compared to that in the NC group (p < 0.05). The percentages of the Treg cells in the BDR and PDR groups were lower than those in NDR group (p < 0.05 in both cases). The percentage of Treg cells in the PDR group was lower than that in the BDR group (p < 0.05). The expression levels of miR-155 in the peripheral blood of the patients in the BDR group, PDR group, and NDR group had significantly increased compared to that in NC group (p < 0.05). The expression levels of miR-155 in the BDR group and PDR group were higher than that in the NDR group (p < 0.05 in both cases). The expression level of miR-155 in the PDR group was higher than that in the BDR group (p < 0.05). The expression levels of TGF-ß in the BDR group and PDR group were significantly decreased compared to those in the NDR group and NC group (p < 0.05 in both cases). The expression of miR-155 was negatively related to the Treg cells and the expression level of TGF-ß2 (r1 = -0.835, p1 = 0.000, r2 = -0.771, p2 = 0.000). CONCLUSIONS: In type 2 diabetes mellitus (T2DM) retinopathy, miR-155 may play an important role in the pathogenesis of T2DM retinopathy by regulating the Treg cells with TGF-ß.

Impact of metabolic syndrome on myocardial injury and clinical outcome after percutaneous coronary intervention.

AIMS: This study tested the associations between metabolic syndrome, postprocedural myocardial injury, and clinical outcome after percutaneous coronary intervention. PATIENTS AND METHODS: We evaluated 204 patients who fulfilled the study criteria and were scheduled for elective percutaneous coronary intervention. The patients were divided into a metabolic syndrome group and a control group according to the definition of metabolic syndrome. Creatine kinase-MB and troponin I levels were measured at baseline, at 8 h, and 24 h after the procedure, while clinical outcomes were followed up for 1 year. RESULTS: The incidence of postprocedural myocardial injury was significantly higher in the metabolic syndrome group than in the control group as indicated by either blood creatine kinase-MB elevation (32.9 % vs. 17.2 %, p = 0.010) or troponin I elevation (34.2 % vs. 17.2 %, p = 0.006). Postprocedural peak values of creatine kinase-MB (5.724 ± 7.678 ng/ml vs. 3.097 ± 5.317 ng/ml, p < 0.001) and troponin I (0.066 ± 0.093 ng/ml vs. 0.038 ± 0.079 ng/ml, p < 0.001) were also significantly higher in the metabolic syndrome group than in the control group. On multiple regression analysis, metabolic syndrome was independently associated with troponin I elevation (odds ratio 2.24, 95 % confidence interval, CI, 1.04-4.80, p = 0.039). During the 1-year follow-up, cardiac events occurred in 28.9 % of patients with metabolic syndrome and 17.9 % of controls, and there was a trend toward increased adverse outcomes in the metabolic syndrome group (hazard ratio 1.67, 95 % CI 0.93-3.00, p = 0.071, log rank test). CONCLUSION: The results of this study demonstrate that metabolic syndrome is associated with postprocedural myocardial injury and with increased cardiac events.

Treatment of distal femur fractures with locking plates: Comparison of periprosthetic fractures above total knee arthroplasty and non-periprosthetic fractures.

The purpose of the present study was to compare the results and plate fit of periprosthetic and non-periprosthetic distal femur fractures fixed with locking plates. Twenty-one periprosthetic fractures above a TKA and 27 non-periprosthetic fractures were retrospectively reviewed. The primary healing rate, bone union time, clinical and radiographic results, complications, and additional surgeries were compared between the two groups. The quality of the plate fit on the bone was also compared. There were no differences in the primary healing rate, bone union time, clinical and radiographic results between the two groups. The incidence of overall complication and additional surgeries did not differ (3/21 vs. 5/27, 1/21 vs. 4/27). Plate fit trouble was observed more frequently in periprosthetic fractures (10/21 vs. 1/27, p = 0.004). Fixation of distal femur fractures with locking plates provided satisfactory results with a low risk of complications and additional surgeries in both periprosthetic and non-periprosthetic fractures.

A novel synthetic compound, 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione, inhibits cisplatin-induced hearing loss by the suppression of reactive oxygen species: in vitro and in vivo study.

Cisplatin, a chemotherapeutic agent for treating various solid tumors, produces hearing loss in approximately half a million cancer patients annually in the United States. In the course of developing a new protective agent against cisplatin-induced ototoxicity, we have been interested in a novel synthetic compound, 3-amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR-22332). The effect of KR-22332 on cisplatin-induced cytotoxicity was analyzed in vitro in an organ of Corti-derived cell line (HEI-OC1), and in vivo in a zebrafish and rat model. Cisplatin-induced apoptosis, reactive oxygen species (ROS) generation and altered mitochondrial membrane potential (MMP) in HEI-OC1 cells were observed. KR-22332 significantly inhibited cisplatin-induced apoptosis, change of MMP, and intracellular ROS generation. KR-22332 markedly attenuated the cisplatin-induced loss and changes of auditory neuromasts in the zebrafish. Transtympanic administration of KR-22332 in a rat model was protective against cisplatin-induced hearing loss, as determined by click-evoked auditory brainstem response (p<0.01). Tissue terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling of rat cochlea demonstrated that KR-22332 blocked cisplatin-induced apoptosis. In addition, transtympanic administration of KR-22332 inhibited cisplatin-induced nicotinamide adenine dinucleotide phosphate-oxidase 3 (NOX3) overexpression in the rat cochlea. KR-22332 significantly reduced the expression of p-53, mitogen-activated protein kinases, caspase 3, and tumor necrosis factor-α compared to their significant increase after cisplatin treatment. The results of this study suggest that KR-22332 may prevent ototoxicity caused by the administration of cisplatin through the inhibition of mitochondrial dysfunction and the suppression of ROS generation. These novel findings implicate KR-22332 as a potential candidate for protective agent against cisplatin-induced ototoxicity.

Serum 1,5-anhydroglucitol is associated with diabetic retinopathy in Type 2 diabetes.

AIMS: To determine whether there is a relationship between 1,5-anhydroglucitol (1,5-AG), a marker of postprandial hyperglycaemia and glycaemic variability, and the presence of diabetic retinopathy and albuminuria in patients with Type 2 diabetes. METHODS: Five hundred and sixty-seven patients with Type 2 diabetes (serum creatinine < 133 µmol/l), who were enrolled in the Seoul Metro-City Diabetes Prevention Program (SMC-DPP), were cross-sectionally assessed by multivariate logistic regression analysis. RESULTS: After controlling for age, sex, binary HbA(1c) levels, duration of diabetes, triglyceride, systolic blood pressure, smoking status, history of hypertension and dyslipidaemia, and the use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker medication, the odds ratios (95% CI) of diabetic retinopathy were 2.86 (1.12-7.25) for the first (lowest) quartile of 1,5-anhydroglucitol, 2.87 (1.25-6.61) for the second quartile and 0.88 (0.35-2.22) for the third quartile compared with the fourth quartile (P for trend = 0.010). Conversely, the associations between 1,5-anhydroglucitol and clinical albuminuria were non-significant after adjustment. Subjects with low 1,5-anhydroglucitol (< 10.0 µg/ml) were more likely to experience diabetic retinopathy than those with high 1,5-anhydroglucitol (≥ 10.0 µg/ml) under moderate glucose control (HbA(1c) < 8%, 64 mmol/mol) and there were no significant differences in the prevalence of diabetic retinopathy between the subgroup with HbA(1c) < 8% (64 mmol/mol) and low 1,5-anhydroglucitol and the subgroup with HbA(1c) ≥ 8% (64 mmol/mol). CONCLUSIONS: 1,5-Anhydroglucitol levels show close associations with diabetic retinopathy, especially among patients under moderate glucose control, but not with albuminuria. These results suggest that 1,5-anhydroglucitol might be a complementary marker for targeting higher risk group.