The relative and combined ability of stress hyperglycemia ratio and N-terminal pro-B-type natriuretic peptide to predict all-cause mortality in diabetic patients with multivessel coronary artery disease.

BACKGROUND: Stress hyperglycemia ratio (SHR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased mortality risk in diabetic patients with coronary artery disease (CAD). However, the role of these biomarkers in patients with diabetes and multivessel disease (MVD) remains unknown. The present study aimed to assess the relative and combined abilities of these biomarkers to predict all-cause mortality in patients with diabetes and MVD. METHODS: This study included 1148 diabetic patients with MVD who underwent coronary angiography at Tianjin Chest Hospital between January 2016 and December 2016. The patients were divided into four groups according to their SHR (SHR-L and SHR-H) and NT-proBNP (NT-proBNP-L and NT-proBNP-H) levels. The primary outcome was all-cause mortality. Multivariate Cox regression analyses were performed to evaluate the association of SHR and NT-proBNP levels with all-cause mortality. RESULTS: During a mean 4.2 year follow-up, 138 patients died. Multivariate analysis showed that SHR and NT-proBNP were strong independent predictors of all-cause mortality in diabetic patients with MVD (SHR: HR hazard ratio [2.171; 95%CI 1.566-3.008; P < 0.001; NT-proBNP: HR: 1.005; 95%CI 1.001-1.009; P = 0.009). Compared to patients in the first (SHR-L and NT-proBNP-L) group, patients in the fourth (SHR-H and NT-proBNP-H) group had the highest mortality risk (HR: 12.244; 95%CI 5.828-25.721; P < 0.001). The areas under the curve were 0.615(SHR) and 0.699(NT-proBNP) for all-cause mortality. Adding either marker to the original models significantly improved the C-statistic and integrated discrimination improvement values (all P < 0.05). Moreover, combining SHR and NT-proBNP levels into the original model provided maximal prognostic information. CONCLUSIONS: SHR and NT-proBNP independently and jointly predicted all-cause mortality in diabetic patients with MVD, suggesting that strategies to improve risk stratification in these patients should incorporate SHR and NT-porBNP into risk algorithms.

[Screening of pathogenic molecular markers of Staphylococcus aureus in children based on whole genome sequencing technology]. / åŸºäºŽå ¨åŸºå› ç»„æµ‹åºæŠ€æœ¯ç­›é€‰å„¿ç«¥é‡‘é»„è‰²è‘¡è„çƒèŒçš„è‡´ç— ç›¸å ³åˆ†å­æ ‡å¿—ç‰©.

OBJECTIVES: To explore the molecular characteristics of Staphylococcus aureus (S. aureus) in children, and to compare the molecular characteristics of different types of strains (infection and colonization strains) so as to reveal pathogenic molecular markers of S. aureus. METHODS: A cross-sectional study design was used to conduct nasopharyngeal swab sampling from healthy children in the community and clinical samples from infected children in the hospital. Whole genome sequencing was used to detect antibiotic resistance genes and virulence genes. A random forest method to used to screen pathogenic markers. RESULTS: A total of 512 S. aureus strains were detected, including 272 infection strains and 240 colonization strains. For virulence genes, the carrying rates of enterotoxin genes (seb and sep), extracellular enzyme coding genes (splA, splB, splE and edinC), leukocytotoxin genes (lukD, lukE, lukF-PV and lukS-PV) and epidermal exfoliating genes (eta and etb) in infection strains were higher than those in colonization strains. But the carrying rates of enterotoxin genes (sec, sec3, seg, seh, sei, sel, sem, sen, seo and seu) were lower in infection strains than in colonization strains (P<0.05). For antibiotic resistance genes, the carrying rates of lnuA, lnuG, aadD, tetK and dfrG were significantly higher in infection strains than in colonization strains (P<0.05). The accuracy of cross-validation of the random forest model for screening pathogenic markers of S. aureus before and after screening was 69% and 68%, respectively, and the area under the curve was 0.75 and 0.70, respectively. The random forest model finally screened out 16 pathogenic markers (sem, etb, splE, sep, ser, mecA, lnuA, sea, blaZ, cat(pC233), blaTEm-1A, aph(3')-III, ermB, ermA, ant(9)-Ia and ant(6)-Ia). The top five variables in the variable importance ranking were sem (OR=0.40), etb (OR=3.95), splE (OR=1.68), sep (OR=3.97), and ser (OR=1.68). CONCLUSIONS: The random forest model can screen out pathogenic markers of S. aureus and exhibits a superior predictive performance, providing genetic evidence for tracing highly pathogenic S. aureus and conducting precise targeted interventions.

Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia.

BACKGROUND: Although androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear. METHODS: The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. RESULTS: The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. CONCLUSION: In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

Co-Immobilization of GOD & HRP on Y-Shaped DNA Scaffold and the Regulation of Inter-Enzyme Distance.

In multienzymes cascade reaction, the inter-enzyme spacing is supposed to be a factor affecting the cascade activity. Here, a simple and efficient Y-shaped DNA scaffold is assembled using two partially complementary DNA single strands on magnetic microspheres, which is used to coimmobilize glucose oxidase (GOD) and horseradish peroxidase (HRP). As a result, on poly(vinyl acetate) magnetic microspheres (PVAC), GOD/HRP-DNA@PVAC multienzyme system is obtained, which can locate GOD and HRP accurately and control the inter-enzyme distance precisely. The distance between GOD and HRP is regulated by changing the length of DNA strand. It showed that the cascade activity is significantly distance-dependent. Moreover, the inter-enzyme spacing is not the closer the better, and too short distance would generate steric hindrance between enzymes. The cascade activity reached the maximum value of 967 U mg-1 at 13.6 nm, which is 3.5 times higher than that of free enzymes. This is ascribed to the formation of substrate channeling.

Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy.

BACKGROUND: High-dose methotrexate (HD-MTX) combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL); however, some patients have adverse reactions. AIM: To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen. METHODS: Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HD-MTX until disease progression, intolerable toxicities, or physician/patient-directed withdrawal. Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria, respectively. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival, overall survival (OS), and safety. RESULTS: The median follow-up duration was 14.7 mo (range, 3.9-30 mo). The ORR for all patients was 84.2%, and 2-year progression-free- and OS rates were 75.6% and 94.1%, respectively. All patients completed the induction phase, and nine patients underwent autologous stem cell transplantation as consolidation therapy, resulting in an ORR of 88.9%. Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%. All patients showed an acceptable safety profile. The sequencing results for cerebrospinal fluid (CSF) and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations. Circulating tumor DNA was correlated with disease relapse and response. CONCLUSION: Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Prognostic performance of multiple biomarkers in patients with acute coronary syndrome without standard cardiovascular risk factors.

Background and aims: Acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) represents a special case of ACS. Multiple biomarkers have been shown to improve risk stratification in patients with ACS. However, the utility of biomarkers for prognostic stratification in patients with ACS without SMuRFs remains uncertain. The aim of the present study was to evaluate the prognostic value of various biomarkers in patents with ACS without SMuRFs. Methods: Data of consecutive patients with ACS without SMuRFs who underwent coronary angiography in Tianjin Chest Hospital between January 2014 and December 2017 were retrospectively collected. The primary outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, myocardial infarction and stroke. Seven candidate biomarkers analyses were analyzed using models adjusted for established risk factors. Results: During a median 5-year follow-up, 81 of the 621 patients experienced a MACE. After adjustment for important covariates, elevated fibrinogen, D-dimer, N-terminal proB-type natriuretic peptide (NT-proBNP), and lipoprotein (a) [Lp(a)] were found to be individually associated with MACE. However, only D-dimer, NT-proBNP and Lp(a) significantly improved risk reclassification for MACE (all P < 0.05). The multimarker analysis showed that there was a clear increase in the risk of MACE with an increasing number of elevated biomarkers and a higher multimarker score. The adjusted hazard ratio- for MACE (95% confidential intervals) for patients with 4 elevated biomarkers was 6.008 (1.9650-18.367) relative to those without any elevated biomarker-. Adding- the 4 biomarkers or the multimarker score to the basic model significantly improved the C-statistic value, the net reclassification index and the integrated discrimination index (all P < 0.05). Conclusion: Fibrinogen, D-dimer, NT-proBNP and Lp(a) provided valuable prognostic information for MACE when applied to patients with ACS without SMuRFs. The multimarker strategy, which combined multiple biomarkers reflecting different pathophysiological process with traditional risk factors improved the cardiovascular risk stratification.

Spatial Bessel-like beams along arbitrary convex trajectories based on a 3D-printed metasurface.

A 3D-printed all-dielectric metasurface is presented in this Letter which can generate an accelerating beam with a circularly symmetric non-spreading transverse profile that can propagate along arbitrary convex trajectories. The curved trajectory is mapped to the corresponding direct-space spatial phases by the basic cube units with different geometrical heights. The required phase distribution is derived in detail based on the enveloping theory of differential geometry and the Bessel beam generation method. A metasurface with a preset trajectory is simulated and measured to demonstrate the validity of the phase distribution calculated by the proposed theory. The full-wave simulation and measurement results verify that the Bessel-like beam whose intensity follows a curved (off-axis) trajectory can be produced by the proposed metasurface. The generated hybrid beam merges the advantages of non-accelerating and accelerating diffractive-free beams. Therefore, the proposed metasurface has great potential in ultrahigh-speed communication, secure communication, near-field imaging, wireless energy transmission applications, and so on. The all-dielectric characteristic provides the proposed metasurface with the competitive advantages of low cost and easy large-scale processing.

[Ecosystem carbon uptake was co-limited by nitrogen and phosphorus in alpine meadow on the Qinghai-Tibet Plateau]. / æ°®ç£·å ±é™åˆ¶é’è—é«˜åŽŸé«˜å¯’è‰ç”¸ç”Ÿæ€ç³»ç»Ÿç¢³å¸æ”¶.

Alpine grassland is threatened by the import of chemicals, fertilizers and other external resources with increasing human activities on the Qinghai-Tibet Plateau. It is unclear how carbon cycle of alpine grasslands is affected by the inputs of external resources such as nitrogen, phosphorus, and potassium (N, P, K) and their interactions. We conducted a 3 year experiment on the interactive addition of N, P and K with alpine grassland as the research object to clarify ecosystem carbon exchange process in response to resource addition by measuring community coverage and ecosystem carbon exchange. The results showed the alpine meadow was represented by carbon sequestration during the growing season. The mean value of net ecosystem CO2 exchange (NEE) was -13.0 µmol·m-2·s-1 under the control treatment. NEE, ecosystem respiration (ER), and gross ecosystem productivity (GEP) showed no significant responses when N, P and K were added separately. NEE was significantly increased by 95.3% and 63.9%, GEP was significantly increased by 45.5% and 33.0% under the combined addition of NP and NPK, but ER remained stable. The combined addition of NP or NPK mainly increased NEE and GEP by increasing the coverage of plant communities and affecting ecosystem water use efficiency. Plant community coverage was increased by 18.1% and 21.4%, respectively. The addition of NP increased productivity and autotrophic respiration in alpine meadow. It might cause soil acidification to inhibit heterotrophic respiration, thereby did not change ER due to the two aspects canceling each other out. The addition of N, P, K alone and NK and PK did not change ecosystem carbon exchange, while the combined addition of NP increased NEE and GEP on the nutrient-deficient alpine meadows, indicating that ecosystem carbon uptake was co-limited by N and P in alpine meadow.

3D printed metasurface for generating a Bessel beam with arbitrary focusing directions.

In this Letter, a metasurface combined with emerging 3D printing technology is proposed. The proposed metasurface regards the simple cube as the unit cell, and the height of the cube is the only variable. A nearly linear transmission phase range covering 360° operating at 20 GHz is obtained when the height is regulated in [2.26 mm, 11.20 mm]. Therefore, the proposed unit cell can be adopted to any metasurface with various functions. Taking the generation of a non-diffractive Bessel beam as an example, two metasurfaces composed of 30×30 units with different focusing directions are designed based on non-diffractive theory and the generalized law of refraction. Two prototypes are 3D printed and measured by a near-field scanning system. The measured results validate our design with satisfactory focusing and beam deflection performance. Additionally, the 3D printed metasurface has lower cost and a shorter processing cycle, and avoids metal loss. Therefore, a 3D printed metasurface is an excellent candidate that can be applied in millimeter wave or even higher frequency bands.

[Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma].

OBJECTIVE: To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL). METHODS: Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m2) for induction treatment, and then 12 cycles of TMZ (150 mg/m2) for maintenance treatment. The day before induction treatment, patients were given rituximab 375 mg/m2 according to their economic status. A retrospective cohort study was performed on patients receiving HD-MTX+TMZ or HD-MTX+TMZ+R to analyze the efficacy and survival. RESULTS: There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed. CONCLUSION: The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.

Primary cardiac lymphoma: the management and outcome of a single-centre cohort of 22 patients.

BACKGROUND: The incidence of primary cardiac lymphoma (PCL) is increasing, but the optimal management approach remains unclear. We assessed the clinical characteristics of a single-centre cohort with the goal of determining the optimal management approach. The treatment outcomes and prognostic factors are reported. MATERIAL AND METHODS: All PCL patients were diagnosed via biopsy guided by whole-body imaging (positron emission tomography/computed tomography [PET/CT] and/or contrast-enhanced CT]. Curative therapy involved either surgery or prephase steroids followed by definitive immunochemotherapy, depending on the histological type. The primary outcomes were overall survival (OS) and progression-free survival (PFS); the secondary outcome was the treatment response. RESULTS: Twenty-two PCL patients (14 males, 8 females; age: 59.5 ± 14.7 years [mean ± S.D.]) were histologically confirmed to have diffuse large B-cell lymphoma (DLBCL; n = 17 [77.3%]), fibrin-associated DLBCL (FA-DLBCL) (n = 4 [18.2%]) and Burkitt lymphoma (n = 1 [4.5%]). Seven patients underwent cardiotomy (three for biopsy, four with curative intent). The median and longest follow-up periods were 16.3 and 180.0 months, respectively. The 16 patients who received curative therapy (complete response [CR], n = 15 [93.8%]; partial response [PR], n = 1 [6.2%]) showed better survival than those who did not (5-year OS: 83.0 ± 11.3% vs. 0%; hazard ratio [HR]: 0.025[95% confidence interval, CI: 0.003-0.187], p < 0.001); 5-year PFS: 78.7 ± 11.0% vs. 0%, HR= 0.010[0.001-0.093], p < 0.001). The left ventricular ejection fractions (LVEF) before and after definitive treatment was 63.6 ± 2.4% and 64.6 ± 4.5%, respectively (p = 0.275, power = 0.318). Extrapericardial lesions were associated with poorer survival (5-year OS: 40.0 ± 29.7% vs. 100%, p = 0.027; 5-year PFS:40.0 ± 21.9% vs. 100%, p = 0.010). CONCLUSIONS: Whole-body imaging is essential for diagnosis and prognosis. Curative therapy provided reasonable outcomes and survival; extrapericardial lesions were associated with a poorer treatment response.

[Clustering and influencing factors of Streptococcus pneumoniae carriage among kindergarten children].

OBJECTIVE: To study the clustering and influencing factors of Streptococcus pneumoniae carriage among kindergarten children, and to provide a scientific basis for the prevention of pneumococcal diseases. METHODS: The multi-stage stratified cluster sampling method was used to collect nasal swabs via the nasal vestibule at both sides from 1 702 kindergarten children in Liuzhou, China. A questionnaire survey was performed on their parents. The chi-square test and the random effects logistic regression analysis were used to analyze data. RESULTS: The carriage rate of Streptococcus pneumoniae was 13.16% (224/1 702) among kindergarten children. The clustering analysis showed that the class-level random effect of Streptococcus pneumoniae carriage was statistically significant (Z=2.07, P=0.038), with an intraclass correlation coefficient of 5.9%. The random effects logistic regression analysis showed that the children aged 5-7 years had a lower risk of Streptococcus pneumoniae carriage than those aged 2-< 5 years (OR=0.55, 95%CI:0.40-0.76, P=0.001), and the children with ≥ 5 family members living together had a higher risk of Streptococcus pneumoniae carriage than those with < 5 family members (OR=1.34, 95%CI:1.01-1.79, P=0.043). CONCLUSIONS: Streptococcus pneumoniae carriage shows a class-level clustering effect, and age and the number of cohabitants are important influencing factors for Streptococcus pneumoniae carriage in children.

Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions.

Compared with other stem cells, human induced pluripotent stem cells-derived neural progenitor cells (iPSC-NPCs) are more similar to cortical neurons in morphology and immunohistochemistry. Thus, they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes. Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury. However, there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons. In this study, we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95% N2 and 5% CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes. Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen- and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium. Additionally, it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons. Further, it increased the length of the longest neurite in the oxygen- and glucose-deprived neurons. These findings validate the hypothesis that exosomes from iPSC-NPCs exhibit a neuroprotective effect on oxygen- and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth. This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (approval No. SRRSH20191010) on October 10, 2019.

Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome.

BACKGROUND: The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS. METHODS: A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2). RESULTS: The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan-Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201-1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019). CONCLUSIONS: The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.

Long-term treatment effect of a modified jailed-balloon technique for de Winter syndrome: a case report.

Timely recognition of the characteristic electrocardiographic pattern of de Winter syndrome is important for providing immediate reperfusion therapy for acute anterior myocardial infarction. In this case, an electrocardiogram showed 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6, with loss of R wave progression in leads V1 to V4. Urgent angiography showed occlusion of the proximal left anterior descending coronary artery and 70% stenosis in the ostial first diagonal branch (Medina type 1.1.1.). For this bifurcation lesion, we successfully performed a modified jailed-balloon technique to protect the side branch during percutaneous coronary intervention stenting. Thereafter, thrombolysis in myocardial infarction 3 flow was restored in both branches. This modified jailed-balloon technique is safe and effective in stent placement for de Winter syndrome without any loss of side branches.

Angiopep-2 conjugated nanoparticles loaded with doxorubicin for the treatment of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor. Its therapeutic efficacy is much lower than that of traditional lymphoma, largely due to the presence of the blood-brain barrier (BBB), which hinders the effective drug delivery and deposition on the disease site. Angiopep-2 (ANG) can target low-density lipoprotein receptor-related protein (LRP) on the surface of brain capillary endothelial cells (BCECs) and exhibits high BBB transport capability. In this study, we designed an ANG conjugated poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) (APP) nanoparticle to deliver doxorubicin (DOX) for the treatment of PCNSL. Our data indicated that the targeted APP nanoparticles showed significantly increased cellular uptake by BCECs compared with the control nanoparticles. In the intracranial SU-DHL-2-LUC lymphoma xenograft mice model, APP enhanced drug deposition in tumor tissues, and DOX-loaded APP (APP@DOX) exhibited a better therapeutic effect than free DOX and nontargeted PP@DOX, which significantly prolonged the survival time of mice.

Diagnostic and prognostic factors for patients with primary pulmonary non-Hodgkin's lymphoma: A 16-year single-center retrospective study.

Primary pulmonary non-Hodgkin's lymphoma (PP-NHL) is a rare entity with non-specific symptoms and radiographic findings, as well as a difficult preoperative diagnosis. A limited number of studies have described PP-NHL in Chinese patients. The goal of the present study was to improve early diagnosis by examining prognostic factors in patients with PP-NHL. Therefore, a total of 29 patients with PP-NHL were included in the study between January 2001 and June 2017, including 14 with aggressive-type and 15 with indolent-type lymphomas (10 male, 19 female; median age, 50.3 years; range, 19-87 years). Pulmonary nodules and masses (55.2%) were the most common radiographic features. The diagnostic yield was 80% (12/15) by endobronchial biopsy or transbronchial lung biopsy and 100% by computed tomography (CT)-guided percutaneous needle lung biopsy (11/11) or surgery (8/8). Elevated lactate dehydrogenase levels and systemic symptoms were observed considerably more often in patients with aggressive disease than in those with indolent disease. The 1-, 3- and 5-year overall survival (OS) rates were 42, 32, and 21%, respectively, for all patients, 72, 57 and 43%, respectively, for patients with indolent lymphomas, and 13, 6 and 0%, respectively, for patients with aggressive lymphomas. The median OS rate for all patients was 12.0 months; however, the OS rate for patients with aggressive lymphomas was significantly shorter compared with those with indolent lymphomas (7.1 months vs. 16.6 months; P=0.002). Aggressive vs. indolent lymphoma status was indicated to be an independent prognostic factor for poor 5-year OS rate (hazard ratio, 5.98; P=0.014). In conclusion, bronchoscopic and CT-guided percutaneous needle lung biopsies were the most useful and least invasive procedures for diagnosing PP-NHL. Furthermore, aggressive PP-NHL was highly associated with poor 5-year OS rate and a poor prognosis.

The prognostic value of total T3 after acute cerebral infarction is age-dependent: a retrospective study on 768 patients.

BACKGROUND: Serum triiodothyronine (T3) concentration was reported to be associated with the prognosis after acute ischemic stroke. The aim of this study was to evaluate the effect of age on the prognostic value of thyroid-related hormones after an acute ischemic stroke. METHODS: This was a retrospective study involving the review of 1072 ischemic stroke patients who had been consecutively admitted to the hospital within 72 h of symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. RESULTS: A total of 768 patients were finally included in the study and divided into two age groups: a younger group (age < 65 years) and an older group (age ≥ 65 years). On univariate analysis, four factors-lower total T3, free T3 concentrations, higher scores on the National Institute of Health Stroke Scale (NIHSS) and the presence of atrial fibrillation-were associated with poor functional outcomes in both groups. In addition, older age, female gender, higher free T4, and lower TSH levels were also associated with poor function in the older group. On multiple logistic regression analysis, higher NIHSS scores (odds ratio [OR] =1.95; 95% confidence interval [CI], 1.66-2.30; P ≤ .001) and lower total T3 concentrations (OR = 0.06; 95% CI, 0.01-0.68; P = .024) remained independently associated with poor functional outcome in the older group. However, the independent association with poor function of lower total T3 was not confirmed in the younger group. CONCLUSIONS: The prognostic value of low total T3 is age-associated and more meaningful in an older population.

Activation of miR-34a-5p/Sirt1/p66shc pathway contributes to doxorubicin-induced cardiotoxicity.

The molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments. Human miR-34a-5p was also observed increased in the plasma of patients with diffuse large B-cell lymphoma after 9- and 16-week epirubicin therapy. Up-regulation of miR-34a-5p was observed in Dox-induced rat cardiomyocyte H9c2 cells. MiR-34a-5p could augment Bax expression, but inhibited Bcl-2 expression, along with the increases of the activated caspase-3 and mitochondrial potentials in H9C2 cells. MiR-34a-5p was verified to modulate Sirt1 expression post-transcriptionally. In parallel to Sirt1 siRNA, miR-34a-5p could enhance p66shc expression, accompanied by increases of Bax and the activated caspase-3 and a decrease of Bcl-2 in H9c2 cells. Moreover, enforced expression of Sirt1 alleviated Dox-induced apoptosis of H9c2 cells, with suppressing levels of p66shc, Bax, the activated caspase-3 and miR-34a-5p, and enhancing Bcl-2 expression. Therefore, miR-34a-5p enhances cardiomyocyte apoptosis by targeting Sirt1, activation of miR-34a-5p/Sirt1/p66shc pathway contributes to Dox-induced cardiotoxicity, and blockage of this pathway represents a potential cardioprotective effect against anthracyclines.