Precise profiling of the sialic acid (SA) expression on the membrane of cancer cells is critical for early identification of cancers and assessment of cancer metastasis. However, the complex ...physiological environments often result in false positives with currently available imaging technologies. Herein, we have established a background-free surface-enhanced Raman scattering (SERS) imaging platform that allows high-precision profiling of SA expression in cancer cells and differentiation of clinically relevant cancer tissues with various metastasis degrees. Three-dimensional Raman imaging technique provided a deeper insight into visualizing the probe distribution and thus the SA expression at the single-cell level, without destructing the cells. This noninvasive, high-precision imaging technique could favor early diagnosis, staging, and monitoring therapeutic responses of cancers that are highly essential in clinical settings.
Elevation of glucose level in response to acute coronary syndrome (ACS) has been recognized as stress induced hyperglycemia (SIH). Plenty of clinical studies have documented that SIH occurs very ...common in patients hospitalized with ACS, even in those without previously known diabetes mellitus. The association between elevated blood glucose levels with adverse outcome in the ACS setting is well-established. Yet, the precise definition of SIH in the context of ACS remains controversial, bringing confusions about clinical management strategy. Several randomized trials aimed to evaluate the effect of insulin-based therapy on outcomes of ACS patients failed to demonstrate a consistent benefit of intensive glucose control. Mechanisms underlying detrimental effects of SIH on patients with ACS are undetermined, oxidative stress might play an important role in the upstream pathways leading to subsequent harmful effects on cardiovascular system. This review aims to discuss various definitions of SIH and their values in predicting adverse outcome in the context of ACS, as well as the effect of intensive glucose control on clinical outcome. Finally, a glimpse of the underlying mechanisms is briefly discussed.
To critically review the currently available evidence of studies comparing robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN).
A comprehensive review of the literature from Pubmed, ...Web of Science and Scopus was performed in October 2013. All relevant studies comparing RPN with OPN were included for further screening. A cumulative meta-analysis of all comparative studies was performed and publication bias was assessed by a funnel plot.
Eight studies were included for the analysis, including a total of 3418 patients (757 patients in the robotic group and 2661 patients in the open group). Although RPN procedures had a longer operative time (weighted mean difference WMD: 40.89; 95% confidence interval CI, 14.39-67.40; p = 0.002), patients in this group benefited from a lower perioperative complication rate (19.3% for RPN and 29.5% for OPN; odds ratio OR: 0.53; 95%CI, 0.42-0.67; p<0.00001), shorter hospital stay (WMD: -2.78; 95%CI, -3.36 to -1.92; p<0.00001), less estimated blood loss(WMD: -106.83; 95%CI, -176.4 to -37.27; p = 0.003). Transfusions, conversion to radical nephrectomy, ischemia time and estimated GFR change, margin status, and overall cost were comparable between the two techniques. The main limitation of the present meta-analysis is the non-randomization of all included studies.
RPN appears to be an efficient alternative to OPN with the advantages of a lower rate of perioperative complications, shorter length of hospital stay and less blood loss. Nevertheless, high quality prospective randomized studies with longer follow-up period are needed to confirm these findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims/Introduction
Neonatal diabetes mellitus is created by alterations in the genes responsible for beta‐cell mass and/or function. The present study aimed to evaluate the genetic variants in the ...insulin gene (INS) in four Chinese infants aged <12 months with diabetes onset, and to explore the clinical and genetic characteristics of permanent neonatal diabetes mellitus caused by INS mutations.
Materials and Methods
The complete coding sequences of KCNJ11, ABCC8 and INS were detected using Sanger sequencing. The pathogenicity of the mutations was determined based on the American College of Medical Genetics and Genomics, and the structure of wild‐type and mutant proteins was predicted using the web‐based tool, Phyre2.
Results
One novel mutation (p.I99_C100insSI) and three previously reported variants (p.G32S, p.R89C and p.C96R) in INS were identified in four infants with early‐onset diabetes. All the mutations in the four patients were de novo. Except for mutation R89C, which causes permanent neonatal diabetes mellitus through the addition of an additional cysteine residue at the cleavage site of the A chain and C‐peptide, the other three mutations affected disulfide bonds. The patients had diabetes with marked hyperglycemia or diabetic ketoacidosis, and were then treated with exogenous insulin. Mutations in crucial regions of the INS might give rise to diabetes with varying severity.
Conclusions
This study enriches our awareness of the mutant spectrum in INS, and suggests the important role of INS in the development of permanent neonatal diabetes mellitus.
In this study, we discovered four mutations in the insulin gene (INS), one of which was novel and was considered to cause permanent neonatal diabetes mellitus. We explored the clinical and genetic characteristics of Chinese permanent neonatal diabetes mellitus caused by INS mutations. This study enriches our awareness of the mutant spectrum in INS, and suggests the important role of INS in the development of permanent neonatal diabetes mellitus.
It is highly expected to develop a simple and effective method to reinforce polyamide 6 (PA6) to enlarge its application potential. This is challenging because of frequently encountered ...multi-component phase separations. In this paper, we propose a novel method to solve this issue, essentially comprising two steps. Firstly, a kind of poly (amide-block-aramid) block copolymers, i.e., thermotropic liquid crystalline polymer (TLCP)-polyamide 6 (TLCP-PA6), that contains both rigid aromatic liquid crystal blocks, and flexible alkyl blocks were synthesized. It is unique in that TLCP is chemically linked with PA6, which is advantageous in excellent chemical and physical miscibility with the precursors of monomer casting polyamide 6 (MCPA6), i.e., ε-caprolactam. Secondly, such newly synthesized block copolymer TLCP-PA6 was dissolved in the melting ε-caprolactam, and followed by in situ polymerization to obtain composite polymer blends, i.e., MCPA6/TLCP-PA6. The thermodynamic, morphological, and crystalline properties of MCPA6/TLCP-PA6 can be easily manipulated by tailoring the loading ratios between TLCP-PA6 and ε-caprolactam. Especially, at the optimized condition, such MCPA6/TLCP-PA6 blends show an excellent miscibility. Systematic characterizations, including nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimeter (DSC), and polarizing optical microscope (POM), were performed to confirm these statements. In view of these results, it is anticipated that the overall mechanical properties of such PA6-based polymer composites will be satisfactory, which should enable applications in the modern plastic industry and other emerging areas, such as wearable fabrics.
Backgrounds:
Emerging evidence suggests that stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is of great prognostic value in acute myocardial infarction (AMI), but ...current evidence is limited in elderly patients. In this study, we aimed to assess whether SHR is associated with in-hospital outcomes in elderly patients with AMI.
Methods:
In this retrospective study, patients who were aged over 75 years and diagnosed with AMI were consecutively enrolled from 2015, January 1st to 2019, December 31th. Admission blood glucose and glycosylated hemoglobin (HbA1C) during the index hospitalization were used to calculate SHR. Restricted quadratic splines, receiver-operating curves, and logistic regression were performed to evaluate the association between SHR and in-hospital outcomes, including in-hospital all-cause death and in-hospital major adverse cardiac and cerebrovascular events (MACCEs) defined as a composite of all-cause death, cardiogenic shock, reinfarction, mechanical complications of MI, stroke, and major bleeding.
Results:
A total of 341 subjects were included in this study. Higher SHR levels were observed in patients who had MACCEs (
n
= 69) or death (
n
= 44) during hospitalization. Compared with a SHR value below 1.25, a high SHR was independently associated with in-hospital MACCEs (odds ratio OR: 2.945, 95% confidence interval CI: 1.626–5.334,
P
< 0.001) and all-cause death (OR: 2.871 95% CI: 1.428–5.772,
P
= 0.003) in univariate and multivariate logisitic analysis. This relationship increased with SHR levels based on a non-linear dose-response curve. In contrast, admission glucose was only associated with clinical outcomes in univariate analysis. In subgroup analysis, high SHR was significantly predictive of worse in-hospital clinical outcomes in non-diabetic patients (MACCEs: 2.716 1.281–5.762,
P
= 0.009; all-cause death: 2.394 1.040–5.507,
P
= 0.040), but the association was not significant in diabetic patients.
Conclusion:
SHR might serve as a simple and independent indicator of adverse in-hospital outcomes in elderly patients with AMI, especially in non-diabetic population.
Inherited dilated cardiomyopathy (DCM) contributes to approximately 25% of idiopathic DCM cases, and the proportion is even higher in familial DCM patients. Most studies have focused on familial DCM, ...whereas the genetic profile of sporadic DCM in Chinese patients remains unknown.
Between June 2018 and September 2019, 24 patients diagnosed with idiopathic DCM without a family history were included in the present study. All patients underwent genetic screening for 80 DCM-related genes using targeted next-generation sequencing.
By in silico analysis, 10 of 99 detected variants were considered pathogenic or likely-pathogenic, including seven TTN truncating variants (TTNtv), one in-frame deletion in TNNT2, one missense mutation in RBM20, and one frameshift deletion variant in FLNC. Of these variants, eight are reported for the first time.
Using targeted next-generation sequencing, potential genetic causes of idiopathic DCM were identified. Sarcomere mutations remained the most common genetic cause of inherited DCM in this cohort of sporadic Chinese DCM.
To explore the possible predicting factors related to prostate cancer and develop a validated nomogram for predicting the probability of patients with prostate cancer.
Clinical data of 697 patients ...who underwent prostate biopsy in Handan Central Hospital from January 2014 to January 2020 were retrospectively collected. Cases were randomized into two groups: 80% (548 cases) as the development group, and 20% (149 cases) as the validation group. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for prostate cancer. The nomogram prediction model was generated using the finalized independent risk factors. Decision curve analysis (DCA) and the area under receiver operating characteristics curve (ROC) of both development group and validation group were calculated and compared to validate the accuracy and efficiency of the nomogram prediction model. Clinical utility curve (CUC) helped to decide the desired cut-off value for the prediction model. The established nomogram with Prostate Cancer Prevention Trial Derived Cancer Risk Calculator (PCPT-CRC) and other domestic prediction models using the entire study population were compared.
The independent risk factors determined through univariate and multivariate logistic regression analyses were: age, tPSA, fPSA, PV, DRE, TRUS and BMI. Nomogram prediction model was developed with the cut-off value of 0.31. The AUC of development group and validation group were 0.856 and 0.797 respectively. DCA exhibits consistent observations with the findings. Through validating our prediction model as well as other three domestic prediction models based on the entire study population of 697 cases, our prediction model demonstrated significantly higher predictive value than all the other models.
The nomogram for predicting prostate cancer can facilitate more accurate evaluation of the probability of having prostate cancer, and provide better ground for prostate biopsy.
MIL-88B(Cr) is a prototypical flexible chromium-based metal-organic framework (MOF), which possesses extremely strong water/thermal stability and excellent “swelling/breathing” ability. However, in ...previous studies, there have been very few reports on MIL-88B(Cr) due to unclear synthesis details. Here, we found that the pure MIL-88B(Cr) can be facile synthesized through a hydrothermal method with the co-use of nitric acid and acetic acid (molar ratio = 1:15). The obtained MIL-88B(Cr) was sufficiently characterized by diverse techniques to assure its high-level quality. This work emphasizes a future valuable approach to expanding the production of flexible Cr-based MOF.
Aims/Introduction
To investigate the clinical and genetic characteristics of Chinese patients with a phenotype consistent with maturity‐onset diabetes of the young type 2 and explore the pathogenic ...mechanism of their hyperglycemia.
Materials and Methods
We studied 12 probands and their extended families referred to our center for screening mutations in the glucokinase gene (GCK). Clinical data were collected and genetic analysis was carried out. The recombinant wild‐type and mutant glucokinase were generated in Escherichia coli. The kinetic parameters and thermal stability of the enzymes were determined in vitro.
Results
In the 12 families, 11 GCK mutations (R43C, T168A, K169N, R191W, Y215X, E221K, M235T, R250H, W257X, G261R and A379E) and one variant of uncertain significance (R275H) were identified. R191W was detected in two unrelated families. Of the 11 GCK mutations, three mutations (c.507G>C, K169N; c.645C>A, Y215X; c.771G>A, W257X; NM_000162.3, NP_000153.1) are novel. Basic kinetics analysis explained the pathogenicity of the five mutants (R43C, K169N, R191W, E221K and A379E), which showed reduced enzyme activity with relative activity indexes between ~0.001 and 0.5 compared with the wild‐type (1.0). In addition, the thermal stabilities of these five mutants were also decreased to varying degrees. However, for R250H and R275H, there was no significant difference in the enzyme activity and thermal stability between the mutants and the wild type.
Conclusions
We have identified 11 GCK mutations and one variant of uncertain significance in 12 Chinese families with hyperglycemia. For five GCK mutations (R43C, K169N, R191W, E221K and A379E), the changes in enzyme kinetics and thermostability might be the pathogenic mechanisms by which mutations cause hyperglycemia.
We examined the clinical and genetic characteristics of 12 Chinese pedigrees suspected with maturity‐onset diabetes of the young type 2 and found 11 different GCK mutations. The function of the mutant enzymes were determined in vitro.
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