Five-year analysis of isolated pathogens and antibiotic resistance of ocular infections from two large tertiary comprehensive hospitals in east China

AIM:To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China.METHODS:Ocular specimen data were collected from January 2019 to October 2023.The pathogen spectrum and positive culture rate for different infection location,such as keratitis,endophthalmitis,and periocular infections,along with antibiotic resistance were analyzed.RESULTS:We included 2727 specimens,including 827(30.33%)positive cultures.A total of 871 strains were isolated,530(60.85%)bacterial and 341(39.15%)fungal strains were isolated.Gram-positive cocci(GPC)were the most common ocular pathogens.The most common bacterial isolates were Staphylococcus epidermidis(25.03%),Staphylococcus aureus(7.46%),Streptococcus pneumoniae(4.59%),Corynebacterium macginleyi(3.44%),and Pseudomonas aeruginosa(3.33%).The most common fungal genera were Fusarium spp.(12.74%),Aspergillus spp.(6.54%),and Scedosporium spp.(5.74%).Staphylococcus epidermidis strains showed more than 50%resistance to fluoroquinolones.Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90%resistance to erythromycin.The percentage of bacteria showing multidrug resistance(MDR)significantly decreased(χ^(2)=17.44,P=0.002).CONCLUSION:GPC are the most common ocular pathogens.Corynebacterium macginleyi,as the fourth common bacterium,may currently be the local microbiological feature of east China.Fusarium spp.is the most common fungus.More than 50%of the GPC are resistant to fluoroquinolones,penicillins,and macrolides.However,the proportion of MDR strains has been reduced over time.

Factors influencing ruminative thinking behaviours in nurses:a cross-sectional study of 858 subjects in a tertiary care hospital

To the editor:Nurses play a vital role in healthcare by providing direct medical care to patients,and their mental well-being significantly impacts the quality of service and patient satisfaction.^(1)Ruminative thinking involves repetitive thoughts about negative feelings,their causes and consequences.This common psychological behaviour innurses can significantly impact their self-evaluation and result in feelings of worthlessness.

Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Traditional Chinese medicine treatment of insomnia based on microbial-gut-brain axis theory

In recent years,insomnia has gradually become a common disease in society,which seriously affects people's quality of life.At present,with the deepening of research on intestinal microbiota-gut-brain axis in Western medicine,many studies suggest that regulating the gastrointestinal tract can treat brain-related diseases.It is found that brain-gut-bacteria axis plays an important role in the prevention and treatment of primary insomnia.At present,although the clinical treatment of insomnia with Western medicine can improve the insomnia symptoms of patients to a certain extent,there are still obvious adverse reactions,such as anxiety and depression,drug addiction,etc.,so long-term oral drug therapy cannot be carried out.Traditional Chinese medicine(TCM)and acu-puncture techniques have certain therapeutic effects on insomnia.TCM believes that the brain and gastrointestinal system are connected through the meridian,and the pathophysiology is closely related.This paper will discuss the theory and feasibility of TCM for the treatment of insomnia from the pathological relation-ship between brain-gut axis,intestinal flora and insomnia.

Thrombin increases the expression of cholesterol 25-hydroxylase in rat astrocytes after spinal cord injury

Astrocytes are important cellular centers of cholesterol synthesis and metabolism that help maintain normal physiological function at the organism level.Spinal cord injury results in aberrant cholesterol metabolism by astrocytes and excessive production of oxysterols,which have profound effects on neuropathology.25-Hydroxycholesterol(25-HC),the main product of the membrane-associated enzyme cholesterol-25-hydroxylase(CH25H),plays important roles in mediating neuroinflammation.However,whether the abnormal astrocyte cholesterol metabolism induced by spinal cord injury contributes to the production of 25-HC,as well as the resulting pathological effects,remain unclear.In the present study,spinal cord injury-induced activation of thrombin was found to increase astrocyte CH25H expression.A protease-activated receptor 1 inhibitor was able to attenuate this effect in vitro and in vivo.In cultured primary astrocytes,thrombin interacted with protease-activated receptor 1,mainly through activation of the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway.Conditioned culture medium from astrocytes in which ch25h expression had been knocked down by siRNA reduced macrophage migration.Finally,injection of the protease activated receptor 1 inhibitor SCH79797 into rat neural sheaths following spinal cord injury reduced migration of microglia/macrophages to the injured site and largely restored motor function.Our results demonstrate a novel regulatory mechanism for thrombin-regulated cholesterol metabolism in astrocytes that could be used to develop anti-inflammatory drugs to treat patients with spinal cord injury.

Associations between Geriatric Nutrition Risk Index,bone mineral density and body composition in type 2 diabetes patients

BACKGROUND Type 2 diabetes mellitus(T2DM),a fast-growing issue in public health,is one of the most common chronic metabolic disorders in older individuals.Osteoporosis and sarcopenia are highly prevalent in T2DM patients and may result in fractures and disabilities.In people with T2DM,the association between nutrition,sarcopenia,and osteoporosis has rarely been explored.AIM To evaluate the connections among nutrition,bone mineral density(BMD)and body composition in patients with T2DM.METHODS We enrolled 689 patients with T2DM for this cross-sectional study.All patients underwent dual energy X-ray absorptiometry(DXA)examination and were categorized according to baseline Geriatric Nutritional Risk Index(GNRI)values calculated from serum albumin levels and body weight.The GNRI was used to evaluate nutritional status,and DXA was used to investigate BMD and body composition.Multivariate forward linear regression analysis was used to identify the factors associated with BMD and skeletal muscle mass index.RESULTS Of the total patients,394 were men and 295 were women.Compared with patients in tertile 1,those in tertile 3 who had a high GNRI tended to be younger and had lower HbA1c,higher BMD at all bone sites,and higher appendicular skeletal muscle index(ASMI).These important trends persisted even when the patients were divided into younger and older subgroups.The GNRI was positively related to ASMI(men:r=0.644,P<0.001;women:r=0.649,P<0.001),total body fat(men:r=0.453,P<0.001;women:r=0.557,P<0.001),BMD at all bone sites,lumbar spine(L1-L4)BMD(men:r=0.110,P=0.029;women:r=0.256,P<0.001),FN-BMD(men:r=0.293,P<0.001;women:r=0.273,P<0.001),and hip BMD(men:r=0.358,P<0.001;women:r=0.377,P<0.001).After adjustment for other clinical parameters,the GNRI was still significantly associated with BMD at the lumbar spine and femoral neck.Additionally,a low lean mass index and higherβ-collagen special sequence were associated with low BMD at all bone sites.Age was negatively correlated with ASMI,whereas weight was positively correlated with ASMI.CONCLUSION Poor nutrition,as indicated by a low GNRI,was associated with low levels of ASMI and BMD at all bone sites in T2DM patients.Using the GNRI to evaluate nutritional status and using DXA to investigate body composition in patients with T2DM is of value in assessing bone health and physical performance.

Effects of steep-axis incision on corneal curvature in onehanded phacoemulsification

AIM: To examine the effects of one-handed phacoemulsification with steep-axis incision on corneal curvature and analyze surgically induced astigmatism(SIA) on the true net power, anterior and posterior corneal surfaces. METHODS: Patients with cataracts underwent onehanded phacoemulsification with a 2.4-mm steep-axis of clear corneal incision(CCI) based on true net power. CCI was created under the guidance of Verion. Central corneal thickness(CCT), keratometry readings of the true net power and anterior and posterior corneal surface were obtained using Pentacam. Biometry, such as axial length, anterior chamber depth(ACD) and white-to-white(WTW) were performed using Lenstar pre-and 3 mo postoperatively. RESULTS: The study evaluated 68 eyes of 65 patients. The mean age was 65.93±9.40 y;CCT was 529.21±37.40 μm;WTW was 11.59±0.35 mm. Regarding true net power, keratometric value at the flattest corneal meridian for the 3-mm central zone(Ks) was significantly decreased postoperatively(P=0.031). Keratometric value at the steepest corneal meridian for the 3-mm central zone(Kf) was increased postoperatively(P>0.05). Astigmatism of true net power was 1.21±0.56 D preoperatively and significantly decreased to 1.02±0.58 D postoperatively(P=0.021). On the anterior corneal surface, no significant difference in Ks and Kf was noted pre-versus postoperatively. Anterior corneal astigmatism was 1.08±0.51 D preoperativelyand significantly decreased to 0.87±0.46 D postoperatively(P=0.002). On the posterior corneal surface, Ks and Kf were significantly increased postoperatively(all P<0.05), and posterior corneal astigmatism also increased(P=0.008). The SIA values of true net power and the anterior and posterior corneal surfaces at 3 mo postoperatively were 1.26±0.63 D(range: 0.11 to 2.80 D), 1.05±0.54 D(range: 0.23 to 2.40 D), and 0.21±0.17 D(range: 0.01 to 0.07 D), respectively. CONCLUSION: One-handed phacoemulsification with steep-axis incision can effectively decrease astigmatism of true net power and anterior corneal astigmatism. In the same surgery, the difference in personal SIA potentially originated from a difference in personal corneal thickness and diameter, both CCT and WTW distance should always be measured preoperatively when planning steep-axis phacoemulsification.

Prevalence and risk factors of diabetic retinopathy in patients with type 2 diabetes in Shanghai

AIM:To investigate the prevalence of diabetic retinopathy(DR)in residents of Shanghai and analyze the risk factors of DR.METHODS:This study involved 7233 patients with diabetes in 2016.The demographic data of the participants were collected using a questionnaire survey.Physical examination,laboratory tests,and ophthalmological examinations were conducted.Two professional ophthalmologists diagnosed and graded DR by fundus examination and then combined the results with fundus images.The unconditional multivariate Logistic regression analysis was used to determine the risk factors.RESULTS:In total,6978 patients with type 2 diabetes in Shanghai with a mean age of 68.33±8.40 y were recruited,including 2975 males(42.6%)and 4003 females(57.4%).Overall,1184 patients were diagnosed with DR,with a prevalence rate of 16.97%.Regression analysis showed that duration of diabetes(OR 1.061,95%CI 1.049-1.073),high systolic blood pressure(SBP;OR 1.071,95%CI 1.037-1.106),increased glycosylated hemoglobin level(OR 1.234,95%CI 1.162-1.311),high blood glucose level(OR 1.061,95%CI 1.023-1.099),increased neutrophil-to-lymphocyte ratio(NLR;OR 1.132,95%CI 1.053-1.217)and mean platelet volume(MPV;OR 1.077,95%CI 1.016-1.142)were risk factors of DR.Conversely,hematocrit(HCT;OR 0.971,95%CI 0.954-0.988)and mean corpuscular volume(MCV;OR 0.980,95%CI 0.965-0.994)were protective factors.CONCLUSION:The prevalence rate of DR in Shanghai is 16.97%.The duration of diabetes,high SBP,increased glycosylated hemoglobin,NLR,and MPV were determined as risk factors of DR.

Identification of a LMNA (c.646C>T) variant by whole-exome sequencing in combination with a dilated cardiomyopathy (DCM) related gene filter in a family with familiar DCM

Dilated cardiomyopathy（DCM）is characterized by the dilated heart chambers and reduced systolic function in the absence of specific aetiology[1].Approximately one third of DCM cases are hereditary.In recent years,DCM concomitant with arrhythmias and sudden death resulting from gene mutation has been widely

Effect of TRAF6 gene silencing on hepatocellular carcinoma cell line SMCC7721 and its possible mechanism

Objective:To explore the effect of TRAF6 gene silencing on the function of hepatocellular carcinoma SMCC7721 and its possible mechanism.Method:Cell lines were constructed by cell transfection technology and verified by quantitative real-time PCR.Cell functional changes were observed by CCK8 method,Transwell test and Method of EdU.Western blotting was used to explore the possible mechanism of action.Result:TRAF6 RNA was abnormally up-regulated in HCC,and TRAF6 levels were detected in both HCC cell lines and L02 cells.SMCC7721 was selected as TRAF6 high expression cell.The results of CCK8 assay and EdU method showed that the decrease of TRAF6 expression significantly inhibited the proliferation of SMCC7721 cells.The results of CCK8 assay and EdU method showed that the decrease of TRAF6 expression significantly inhibited the proliferation of SMCC7721 cells.Overexpression of TRAF6 in TRAF6 knockdown cells can restore and enhance cell proliferation.Transwell assay confirmed that the invasiveness of SMCC 7721 cells treated with siRNA was significantly reduced.After treatment with LV-Rescue plasmid,the cell invasion was restored and enhanced.Western blotting showed that the protein levels of YB-1,Wnt,β-catenin,c-myc and Cyclin D1 were significantly down-regulated in siRNA group.On the contrary,the expression level of CYLD protein increased.Conclusion:As an important intracellular junctive protein in tumor cells,TRAF6 may improve the expression of pro-cancer factors C-myc and Cyclin D1 by modifying(ubiquitination)YB-1,thus improving the proliferation ability of cells.This process may be closely positively correlated with the Wnt/β-catenin pathway,and negatively correlated with the expression of CYLD protein.

Role of clinical data and multidetector computed tomography findings in acute superior mesenteric artery embolism

BACKGROUND Superior mesenteric artery embolism(SMAE)has acute onset and fast progression,which seriously threatens the life of patients.Multidetector computed tomography(MDCT)is one of the most important diagnostic methods for SMAE,which plays an important role in the diagnosis and prognosis of SMAE.AIM To evaluate the value of combined clinical data and MDCT findings in the diagnosis of acute SMAE and predict the risk factors for SMAE-related death.METHODS Data from 53 SMAE patients who received abdominal MDCT multi-phase enhancement and superior mesenteric artery digital subtraction angiography examinations were collected.Univariate cox regression and multivariate cox model were used to analyze the correlation between death risk and clinical and computed tomography features in SMAE patients.RESULTS Univariate Cox regression model showed that intestinal wall thinning,intestinal wall pneumatosis,blood lactate>2.1 mmol/L and blood pH<7.35 increased the risk of death in patients with SMAE.After adjusting for age,sex,embolic involvement length and embolic distribution region,multivariate Cox regression model I showed that blood lactate>2.1 mmol/L(HR=5.26,95%CI:1.04-26.69,P=0.045)and intestinal wall thinning(HR=9.40,95%CI:1.05-83.46,P=0.044)were significantly increases the risk of death in patients with SMAE.CONCLUSION For patients with SAME,increased blood lactate and intestinal wall thinning are the risk factors for death;hence,close monitoring may reduce the mortality rate.Clinical observation combined with MDCT signs can significantly improve SMAE diagnosis.

Structure,ligands,and roles of GPR126/ADGRG6 in the development and diseases

Adhesion G protein-coupled receptors(aGPCRs)are the second largest diverse group within the GPCR superfamily,which play critical roles in many physiological and patho-logical processes through cell-cell and cell-extracellular matrix interactions.The adhesion GPCR Adgrg6,also known as GPR126,is one of the better-characterized aGPCRs.GPR126 was previously found to have critical developmental roles in Schwann cell maturation and its mediated myelination in the peripheral nervous system in both zebrafish and mammals.Current studies have extended our understanding of GPR126-mediated roles during develop-ment and in human diseases.In this review,we highlighted these recent advances in GPR126 in expression profile,molecular structure,ligand-receptor interactions,and associated physiological and pathological functions in development and diseases.

转腺病毒-人骨形态发生蛋白7软骨细胞分泌的透明质酸和Ⅱ型胶原

背景:软骨细胞自身分裂能力不强和去分化现象限制了其在组织工程中的应用。目的:观察腺病毒-骨形态发生蛋白7转染兔软骨细胞后骨形态发生蛋白7的表达及其对软骨细胞分泌Ⅱ型胶原和透明质酸功能的影响。方法:包装骨形态发生蛋白7腺病毒载体,将其转染至兔第2代软骨细胞。检测骨形态发生蛋白7mRNA及蛋白的表达;检测软骨细胞中Ⅱ型胶原和透明质酸的变化。结果与结论:转染腺病毒-骨形态发生蛋白7后48,72h,RT-PCR和Western blot方法显示软骨细胞表达的骨形态发生蛋白7mRNA和蛋白均明显增加,RT-PCR和ELISA显示软骨细胞分泌的Ⅱ型胶原和透明质酸也显著增加。说明应用腺病毒可成功将骨形态发生蛋白7转染至兔软骨细胞,并能促进软骨细胞分泌Ⅱ型胶原和透明质酸。

Sick sinus syndrome associated with hypopituitarism:a case report and literature review

Though an association between autoimmune diseases and sick sinus syndrome has been reported,there has been no report on the association of hypopituitarism and sick sinus syndrome.Herein,we provide the first case report of hypopituitarism accompanying sick sinus syndrome in a 51-year-old woman presented to our hospital with syncope due to cardiac arrest.The patient was successfully managed by pacemaker installation and hormone replacement therapy.

Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration

Tissue regeneration requires exogenous and endogenous signals,and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells.The short-distance peripheral nerve showed a spontaneous regenerative phenomenon,which was initiated by the guiding role of macrophages.However,it cannot sufficiently restore long-distance nerve injury by itself.Based on this principle,we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves.Furthermore,a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles(EVs).The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner.The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells,neuron growth and motor function recovery.Meanwhile,the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction.Overall,we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve.This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment,favoring long-distance peripheral nerve regeneration.It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration,which facilitating the development of pro-regenerative biomaterials.

Rectangular 3-snip punctoplasty versus punch punctoplasty with silicone intubation for acquired external punctal stenosis:a prospective randomized comparative study

AIM:To evaluate the effectiveness of rectangular 3-snip punctoplasty versus punch punctoplasty via Kelly punch with silicone intubation for the management of acquired external punctal stenosis(AEPS).METHODS:A prospective,randomized,comparative study was performed on 123 eyes of 94 patients with AEPS.Patients were recruited into either group of rectangular 3-snip punctoplasty(group A)or group of punch punctoplasty with silicone intubation(group B).Outcomes measured were Munk score,grade of punctal stenosis,fluorescein dye disappearance time test(FDDT)and tear meniscus height(TMH)6 and 12 mo after surgery.RESULTS:Twelve months after surgery,Munk score,FDDT and TMH significantly decreased in both groups compared with the baseline(all P<0.05),and grade of punctal stenosis increased significantly(P<0.05).The grade of punctal stenosis,Munk score,FDDT and TMH were better in group B compared with group A at 6 or 12 mo(all P<0.05).There was a positive correlation between TMH and Munk score(R=0.655,P<0.001).At the last followed-up,anatomical success was noted in 96.7%eyes in group A and 98.4%eyes in group B(P=0.613).CONCLUSION:Punch punctoplasty via Kelly punch with silicone intubation achieves better outcomes than rectangular 3-snip punctoplasty.The new technique is a simple,minimally invasive,with high anatomical and functional success in patients with AEPS.

High expression of FABP4 in colorectal cancer and its clinical significance

Objective:To investigate the relationship between the fatty acid-binding protein 4(FABP4)and colorectal cancer(CRC).Methods:Using an enzyme-linked immunosorbent assay(ELISA),we measured the expression of FABP4 in plasma of50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls.The content of the visceral fat area(VFA)as seen with abdominal computed tomography(CT)scanning was measured by ImageJ software.The expression levels of FABP4,E-cadherin,and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.Results:The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group(22.46 vs.9.82 ng/m L;P<0.05).The concentration of plasma FABP4 was related to the tumor,node,metastatis(TNM)stage and lymph node metastasis and was independent of age,body mass index(BMI),tumor size and location,and the degree of differentiation of CRC.The concentration of plasma FABP4 was positively correlated with high VFA and lipoprotein-a(LPA)(P<0.05);but it was not correlated with total cholesterol(TG),total triglyceride(TC),low-density lipoprotein(LDL),high-density lipoprotein(HDL),or apolipoprotein AI(Apo-AI).The expression of FABP4 protein in CRC tissues was positively correlated with the degree of CRC differentiation,tumor stage,and lymph node metastasis.The level of FABP4 protein was negatively correlated with E-cadherin protein(r=-0.3292,P=0.0196)and positively correlated with Snail protein(r=0.5856,P<0.0001).Conclusions:High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients.FABP4 protein was highly expressed in CRC tissues and associated with TNM stage,differentiation,and lymph node metastasis of CRC.The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression,suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition(EMT).

Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation

Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections,such as Epstein-Barr virus.Epstein-Barr virus is a γ-herpesvirus and is related to many malignant diseases,especially epithelial and lymph tumors.The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells.This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation.Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells.Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos.5,8,9,and 10,particularly in sample No.5.Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus.The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells in vitro.Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells,which may be involved in the anti-apoptosis activity of the infected cells.Confocal microscopy showed that pairs of molecules of cluster of differentiation 40,cluster of differentiation 40 ligand,and latent membrane protein 1 were colocalized on the surface of the infected cells.CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection.The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α.Anti-apoptosis and migration are known important biological characteristics of malignant cells.Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma.The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center,which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.

Predicting the pathological status of mammographic microcalcifications through a radiomics approach

Objective The study aimed to develop a machine learning(ML)-coupled interpretable radiomics signature to predict the pathological status of non-palpable suspicious breast microcalcifications(MCs).Methods We enrolled 463 digital mammographical view images from 260 consecutive patients detected with non-palpable MCs and BI-RADS scored at 4(training cohort,n=428;independent testing cohort,n=35)in the First Affiliated Hospital of Nanjing Medical University between September 2010 and January 2019.Subsequently,837 textures and 9 shape features were subsequently extracted from each view and finally selected by an XGBoostembedded recursive feature elimination technique(RFE),followed by four machine learning-based classifiers to build the radiomics signature.Results Ten radiomic features constituted a malignancy-related signature for breast MCs as logistic regression(LR)and support vector machine(SVM)yielded better positive predictive value(PPV)/sensitivity(SE),0.904(95%CI,0.865–0.949)/0.946(95%CI,0.929–0.977)and 0.891(95%CI,0.822–0.939)/0.939(95%CI,0.907–0.973)respectively,outperforming their negative predictive value(NPV)/specificity(SP)from 10-fold crossvalidation(10FCV)of the training cohort.The optimal prognostic model was obtained by SVM with an area under the curve(AUC)of 0.906(95%CI,0.834–0.969)and accuracy(ACC)0.787(95%CI,0.680–0.855)from 10FCV against AUC 0.810(95%CI,0.760–0.960)and ACC 0.800 from the testing cohort.Conclusion The proposed radiomics signature dependens on a set of ML-based advanced computational algorithms and is expected to identify pathologically cancerous cases from mammographically undecipherable MCs and thus offer prospective clinical diagnostic guidance.

Glycemic variability in insulin treated type 2 diabetes with well-controlled hemoglobin Alc and its response to further treatment with acarbose

Background Glycemic variability, an HbAlc-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus （T2DM） with HbAlc 〈6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose. Methods Eighty-six T2DM patients who used premixed insulin analogue （insulin aspart 30） twice daily and had HbAlc 〈6.5% and 20 controlled subjects with normal glucose regulation （NGR） were monitored using the continuous glucose monitoring （CGM） system. The mean amplitude of glycemic excursions （MAGE）, mean of daily differences （MODD） were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level 〈3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups： Iow-MAGE group with MAGE 〈3.4 mmol/L （L-MAGE） and high-MAGE group with MAGE 〉3.4 mmol/L （H-MAGE）. H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system. Results After first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR （P 〈0.01）. Twenty-four percent （n=11） in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% （n=-2） in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night （hypoglycemic events： 24% vs. 5%, X2=6.40, P 〈0.01）. MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value （r=-0.32 and 0.26, respectively, P 〈0.05）. After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased （40%, P 〈0.01, and 15%, P 〈0.05, respectively）, but remained higher than in the subjects with NGR （P 〈0.05）; 2% （n=-l） had a total of 1 hypoglycemic event, incidence significantly decreased （2% vs. 24%, X2=9.61, P 〈0.01）. Conclusions CGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbAlc in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.