Thyroxine promotes the progression of integrin α vβ 3-positive differentiated thyroid cancer through the ERK1/2 pathway / 中华核医学与分子影像杂志

Objective:To explore whether thyroxine (T 4) could promote differentiated thyroid cancer (DTC) progression by binding to integrin α vβ 3in vitro and its downstream mechanism. Methods:Papillary thyroid cancer cell lines TPC-1, K1 and follicular thyroid cancer (FTC) cell line FTC133 were cultured in vitro, and the expressions of integrin α vβ 3 in those 3 DTC cell lines were determined with immunofluorescence and flow cytometry analysis. After the treatment of T 4, tetraiodo thyroacetic acid (Tetrac) and Arg-Gly-Asp (RGD) peptide alone or in combination, the proliferation and metastatic potential of DTC cell lines were detected by cell counting kit-8 (CCK-8), Transwell migration and invasion assays. The small interfering RNA (siRNA) transfection was used to verify whether integrin α v or β 3 subunit knockdown could reverse the effect of T 4 on DTC cells. The expression levels of downstream signaling proteins phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and total extracellular signal-regulated kinase (ERK)1/2 were detected by Western blot. The effects of mitogen-activated protein kinase kinase (MEK)1/2 inhibitor (GSK1120212) on the proliferation, migration and invasion of T 4-treated cells were detected. One-way analysis of variance and Tukey test were used for data analysis. Results:The integrin α vβ 3 expressions in TPC-1, K1 and FTC133 cells were all positive, with the relative mean fluorescence intensity (MFI) of 61.93±18.61, 16.89±2.43 and 32.36±0.83, and the percentages of positive cells of (94.38±1.30)%, (74.11±3.87)% and (50.67±1.78)%, respectively ( F values: 13.36 and 217.30, P=0.006 and P<0.001). Compared with control group, the proliferation, migration and invasion in the three DTC cell lines treated with T 4 were significantly enhanced (96 h, F values: 62.67-297.50, q values: 13.15-20.73, all P<0.001). T 4-induced cell proliferation, migration and invasion were markedly reversed by Tetrac or RGD (96 h, q values: 8.61-17.54, all P<0.001). T 4-induced cell proliferation, migration and invasion were also significantly inhibited by the knockdown of integrin α v or β 3 subunit (72 h, F values: 7.75-70.98, q values: 4.77-15.21, all P<0.05). Western blot results showed that the phosphorylation levels of ERK1/2 in DTC cells were significantly increased by T 4 treatment, and the T 4-induced activation of ERK1/2 signaling pathway could be blocked by Tetrac, RGD, integrin α v or β 3 subunit knockdown. T 4-induced cell proliferation, migration and invasion were significantly reversed by GSK1120212 (96 h, F values: 47.53-151.40, q values: 10.32-16.65, all P<0.001). Conclusion:T 4 can promote cell proliferation and metastasis of DTC cells by binding to integrin α vβ 3 and activating the ERK1/2 pathway.

Application of limiting antigen avidity enzyme immunoassay for estimating HIV-1 incidence in men who have sex with men / 中华流行病学杂志

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.

Research Advances of Acquired Thrombotic Thrombocytopenic Purpura--Review / 中国实验血液学杂志

Thrombotic thrombocytopenic purpura (TTP) is an acute, potentially life-threatening thrombotic microangiopathies (TMA). TTP has mainly been diagnosed by clinical findings, such as thrombocytopenia and microangiopathic haemolytic anemia. In addition, the reduced activity of von Willebrand factor-cleaving metalloproteinase ADAMTS13 below 10% has been accepted internationally as a diagnostic criterion for TTP. In clinic, the accurate diagnosis and early initiation of therapy can significantly improve the survival rate of patients. Therapy should be focused on increasing ADAMTS13 activity and eliminating or inhibiting ADAMTS13 antibody by the infusion or exchange of therapeutic plasma and corticosteroids. Both the administration of recombinant ADAMTS13 and reducing the release of human neutrophil peptides (HNPs) would be novel promising strategies for the prevention of platelet-vWFinteraction. This review briefly summarizes the recent advances in terms of pathogenesis, diagnosis and treatment of TTP.

Clinical analysis of primary gastrointestinal non-hodgkin's lymphoma

Objective: To study the clinical characteristics and prognostic factors of survival for patients with primary gastrointestinal non-Hodgkin's lymphoma [PGI-NHL]

Methods: A retrospective analysis was performed for 104 PGI-NHL patients who were admitted in Baoding First Central Hospital from July 2003 to January 2014

Results: There were 58 males and 46 females. The median age of onset was 53 [15-83] years old. In terms of pathogenic sites, there were 51 gastric cases [49.00%] and 53 intestinal cases [51.00%], with the median survival of 35 [1-130] months. The 1-, 3- and 5-year overall survival [OS] rates were 88.40%, 80.70% and 78.80%, respectively. The factors influencing the progression-free survival [PFS] and OS rates were studied by univariate and multivariate analyses. The PFS and OS rates of patients with B-cell PGI-NHL were significantly higher than those of patients with T-cell PGI-NHL [P<0.05]. The PFS and OS rates of patients with primary gastric lymphoma were significantly higher than those of patients with primary intestinal lymphoma [P<0.05], but the data were not associated with Ann Arbor stage or LDH level [P>0.05]. Compared with non-surgical patients, only patients with intestinal lymphoma benefited from surgery [P<0.05]

Conclusion: The pathogenic site and pathological type are risk factors that affect the survival of PGI-NHL patients, and chemotherapy should be given the first priority for patients with primary gastric lymphoma

Different diagnostic efficacy of solitary pulmonary nodules in 99 Tcm-MIBI SPECT/CT varient background selected / 西安交通大学学报(医学版)

Objective To assess the diagnostic accuracy of solitary pulmonary nodules while selecting different backgrounds in 99 Tcm‐MIBI SPECT/CT examination .Methods Totally 38 suspected solitary pulmonary nodules (SPN) were analyzed retrospectively .The lesions were divided into malignant group and benign group according to the pathological findings . We selected two different backgrounds , contralateral lung field ( DL ) and the contralateral soft tissue (NST) .The maximum counts and the mean counts of lesion to non‐lesion ratio (L/N) were calculated to evaluate diagnostic efficacy using ROC curve . The relationship between lesion size , pathological grading and L/N ratio was analyzed by Spearman correlation analysis . Results With DL and NST as the backgrounds ,the maximum counts and the mean counts of L/N between benign and malignant groups both differed significantly (all P0 .05) .The size and pathological grading of SPN did not affect 99 Tcm‐MIBI accumulation in the SPN (all P>0 .05) .Conclusion DL and NST both can be used as the background in diagnosis of pulmonary nodules on 99 Tcm‐MIBI SPECT/CT examination .The mean counts of the contralateral tissue used as the background can provide a stable result and a high diagnostic accuracy to assess the SPN .

Diagnostic efficacy of 99Tcm-MIBI SPECT/CT and 18F-FDG coincidence SPECT/CT for solitary pulmonary nodules: a comparative study / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the diagnostic accuracy of (99)Tc(m)-MIBI SPECT/CT and (18)F-FDG coincidence SPECT/CT for solitary pulmonary nodules.</p><p><b>METHODS</b>A total of 88 cases suspected of solitary pulmonary nodules were analyzed retrospectively, of whom 36 were examined with (18)F-FDG coincidence SPECT/CT and 52 with (99)Tc(m)-MIBI SPECT/CT. The nature of the solitary pulmonary nodules (malignant or benign) were determined according to the pathological or follow-up (>2 years) results. The diagnostic accuracy of the two modalities for solitary pulmonary nodules was evaluated by ROC curve. The correlation of the lesion size and pathological grade determined by the two modalities with the L/N ratio was assessed using Spearman correlation analysis.</p><p><b>RESULTS</b>(18)F-FDG coincidence SPECT/CT and (99)Tc(m)-MIBI SPECT/CT showed a similar area under curve (AUC) of the L/N ratio (0.92 vs 0.88, P=0.565) with diagnostic sensitivities of 76.92% (20/26) and 80.77% (21/26) and specificities of 100% (10/10) and 88.46% (23/26), respectively. For solitary pulmonary nodules with lesion diameter ≤2 cm, the AUC was 1.00 with (18)F-FDG coincidence SPECT/CT and 0.90 with (99)Tc(m)-MIBI SPECT/CT (P=0.746), while for nodules beyond 2 cm but below 3 cm, the AUCs were 0.79 and 0.89, respectively (P<0.001). In either of the two modalities, correlation analysis revealed no correlation of the L/N ratio with the pathological grade of the malignant lesions (P=0.771 and 0.077, respectively). The L/N ratio was not correlated with the size of the malignant lesion detected by (99)Tc(m)-MIBI SPECT/CT (P=0.516) but was significantly correlated with the size of the malignant lesions detected by (18)F-FDG coincidence SPECT/CT (P=0.016).</p><p><b>CONCLUSION</b>(99)Tc(m)-MIBI SPECT/CT has a greater diagnostic accuracy than (18)F-FDG coincidence SPECT/CT for solitary pulmonary nodules with lesion a diameter beyond 2 cm, and is therefore the primary choice for low-income patients.</p>

Lipofuscin-and melanin-related fundus auto-fluorescence in patients with central serous chorioretinopathy / 中华实验眼科杂志

Background Auto-fluorescence(AF)imaging is a new non-invasive fundus examining technology.It is now playing an increasingly important role in the diagnosis of retinal diseases.Using a confocal Scanning Laser Ophthalmoscope microscope(cSLO),two types of AF can be obtained:melanin-related near-infrared fundus auto-fluorescence(NIA)and lipofuscin-related fundus auto-fluorescence(FAF).Objective The purpose of this study was to compare the outcome between NIA and FAF in patients with central serous chorioretinopathy (CSC).Methods FAF,NIA imaging and fundus fluorescein angiography(FFA)were performed on 28 eyes of 23 subjects using a cLSO.AF images were evaluated and compared with angiographic findings.Written informed consent was obtained before the initiation of this study.Results In 17 eyes of 15 cases with acute CSC,the leakage points on the FFA image showed three kinds of AF patterns:(1)hyper-AF,including FAF hyper-AF in 2 eyes(11.76％)and NIA hyper-AF in 4 eyes(23.53％).(2)Non-AF,including FAF non-AF in 10 eyes(58.82％)and NIA non-AF in 13 eyes(76.47％).(3)Normal AF,including normal AF of FAF in 5 eyes(29.42％).The AF in the retinal serous detachment area showed two kinds of characteristics:(1)hypo-AF,including 12 eyes(70.59％)with FAF hypo-AF and 10 eyes(58.82％)with NIA hypo-AF.(2)hyper-AF,including 5 eyes(29.41％)with FAF hyper-AF and 7 eyes (41.18％)with NIA hyper-AF.In 11 eyes of 8 cases with chronic CSC,the leakage on the FFA also showed an absence of AF.However,AF-absent areas also partly appeared in the non-leakage area of FFA.In NIA,the non-AF areas were often more visible than that in FAF.Serous detachment areas in chronic CSC usually displayed multiple AF forms,including granular-like non-AF,hyper-AF and hypo-AF,and the abnormal AF areas were often greater than that of the corresponding abnormal fluorescent area in FFA.Conclusions AF can be used to detect the functional status and metabolic activity of RPE in CSC eyes.

Characteristics of fundus autofluorscence in patients with atrophic age-related macular degeneration / 中华实验眼科杂志

Background The early diagnosis and treatment is vital for the age-related macular degeneration (AMD).Previous examining methods were fundus fluorescein angiography(FFA)and optical coherence tomography (OCT).However,a new diagnostic technique,fundus autofluorescence(FAF),is applying in ophthalmology.objective This study was to observe the FAF characteristics of atrophic AMD. Methods Thirty-nine eyes of 28 patients with atrophic AMD were diagnosed and collected in our hospital and classified based on the criteria of Chen Song.FAF was performed by a confocal scanning laser ophthalmoscope(Heidelberg Retina Angiograph 2,HRA2).Characteristics of FAF images were compared with FFA images or color fundus photographs.Written informed consent was obtained from each patient prior to the examination. Results Areas with abnormal increased or decreased FAF signals were consisted or unconsisted with funduscopically visible alterations.Seven manifestations of FAF were found in the eyes with preatrophic stage of atrophic AMD,including slight change,focal increase pattern,patchy pattern,linear pattern,lacelike pattern,reticular pattern,and speckled pattern.In atrophic stage of atrophic AMD,geographic atrophy showed a well-defined hypoautofluorescence area;while non-geographic atrophy showed a ill-defined hypoautofluorescence area.There were three abnormal FAF patterns(focal,band and diffuse)in the junctional zone of geographic atrophy and diffuse pattern in the junctional zone of non-geographic atrophy. Conclusion FAF imaging is helpful for the diagnosis of atrophic AMD as a new non-invasive technique.

Characteristics of fundus autofluorescence in cystoid macular edema / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fundus autofluorescence (FAF) imaging is a fast and noninvasive technique developed over the last decade. The authors utilized fluorescent properties of lipofuscin to study the health and viability of the retinal pigment epithelium (RPE)-photoreceptor complex. Observing the intensity and distribution of FAF of various retinal diseases is helpful for ascertaining diagnosis and evaluating prognosis. In this study, we described the FAF characteristics of cystoid macular edema (CME).</p><p><b>METHODS</b>Sixty-two patients (70 eyes) with CME were subjected to FAF and fundus fluorescein angiography (FFA) by a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2 (HRA2)). Characteristics of FAF images were compared with FFA images.</p><p><b>RESULTS</b>FAF intensity in normal subjects was highest at the posterior pole and dipped at the fovea. All cases of CME showed fluorescein dye accumulated into honeycomb-like spaces in macular and formated a typical petaloid pattern or atypical petaloid pattern in the late phases of the angiography. Sixty-one eyes with CME on FAF images showed mild or moderate hyperautofluorescence petaloid pattern in fovea, the FAF patterns of these CME was perfectly corresponding with shape in their FFA images; nine eyes with CME secondary to exudative age related macular degeneration (AMD) showed expansion of the hypoautofluorescence without petaloid pattern in macula.</p><p><b>CONCLUSION</b>FAF imaging can be used as a new rapid, non-invasive and ancillary technique in the diagnosis of the majority of CME, except for AMD and small part of other fundus diseases.</p>

Searching for genes interacting with human PCIA1 gene by using the bacterial two-hybrid system / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To search for the genes which could interact with newly found homo sapiens cross-immune reaction antigen (PCIA1) gene and accordingly to provide insights into the study of the gene function.</p><p><b>METHODS</b>The Stratagene's BacterioMatch Two-Hybrid System and BacterioMatch Fetal Kidney Library were adopted and the recombinant bait plasmid pBT-PCIA1 was cotransformated with the target plasmid pTRG-cDNA library DNA into the reporter stain. After screening and isolation of positive pTRG clones, the target genes were identified by DNA sequencing and bioinformation analysis.</p><p><b>RESULTS</b>Among all the seven detected target genes, three genes' function were not known, the other four genes had important functions. Their mutations or abberant expression resulted in severe diseases and overexpression of ACTN4 (actinin, alpha 4), PSAP (prosaposin) or EIF3S10 (eukaryotic translation initiation factor 3, subunit 10 theta) could promote tumor development and progression.</p><p><b>CONCLUSION</b>The bacterial two-hybrid system technique is an efficient method, which can provides insights into the study of novel genes' function by detecting protein-protein interactions. This study indicates that PCIA1 gene expression correlates with tumor formation, invasion and metastasis.</p>