VSG-GAN: A high-fidelity image synthesis method with semantic manipulation in retinal fundus image.

In recent years, advancements in retinal image analysis, driven by machine learning and deep learning techniques, have enhanced disease detection and diagnosis through automated feature extraction. However, challenges persist, including limited data set diversity due to privacy concerns and imbalanced sample pairs, hindering effective model training. To address these issues, we introduce the vessel and style guided generative adversarial network (VSG-GAN), an innovative algorithm building upon the foundational concept of GAN. In VSG-GAN, a generator and discriminator engage in an adversarial process to produce realistic retinal images. Our approach decouples retinal image generation into distinct modules: the vascular skeleton and background style. Leveraging style transformation and GAN inversion, our proposed hierarchical variational autoencoder module generates retinal images with diverse morphological traits. In addition, the spatially adaptive denormalization module ensures consistency between input and generated images. We evaluate our model on MESSIDOR and RITE data sets using various metrics, including structural similarity index measure, inception score, Fréchet inception distance, and kernel inception distance. Our results demonstrate the superiority of VSG-GAN, outperforming existing methods across all evaluation assessments. This underscores its effectiveness in addressing data set limitations and imbalances. Our algorithm provides a novel solution to challenges in retinal image analysis by offering diverse and realistic retinal image generation. Implementing the VSG-GAN augmentation approach on downstream diabetic retinopathy classification tasks has shown enhanced disease diagnosis accuracy, further advancing the utility of machine learning in this domain.

Genome-wide identification and functional characterization of borneol dehydrogenases in Wurfbainia villosa.

MAIN CONCLUSION: Genome-wide screening of short-chain dehydrogenases/reductases (SDR) family reveals functional diversification of borneol dehydrogenase (BDH) in Wurfbainia villosa. Wurfbainia villosa is an important medicinal plant, the fruits of which accumulate abundant terpenoids, especially bornane-type including borneol and camphor. The borneol dehydrogenase (BDH) responsible for the conversion of borneol to camphor in W. villosa remains unknown. BDH is one member of short-chain dehydrogenases/reductases (SDR) family. Here, a total of 115 classical WvSDR genes were identified through genome-wide screening. These WvSDRs were unevenly distributed on different chromosomes. Seven candidate WvBDHs based on phylogenetic analysis and expression levels were selected for cloning. Of them, four BDHs can catalyze different configurations of borneol and other monoterpene alcohol substrates to generate the corresponding oxidized products. WvBDH1 and WvBDH2, preferred (+)-borneol to (-)-borneol, producing the predominant ( +)-camphor. WvBDH3 yielded approximate equivalent amount of (+)-camphor and (-)-camphor, in contrast, WvBDH4 generated exclusively (+)-camphor. The metabolic profiles of the seeds showed that the borneol and camphor present were in the dextrorotatory configuration. Enzyme kinetics and expression pattern in different tissues suggested WvBDH2 might be involved in the biosynthesis of camphor in W. villosa. All results will increase the understanding of functional diversity of BDHs.

High-solids enzymatic saccharification of starch-rich raw herbal biomass residues for producing high titers of glucose.

The bioresource utilization of herbal biomass residues (HBRs) has been receiving more attention. Herein, three different HBRs from Isatidis Radix (IR) and Sophorae Flavescentis Radix (SFR) and Ginseng Radix (GR) were subjected to batch and fed-batch enzymatic hydrolysis to produce high-concentration glucose. Compositional analysis showed the three HBRs had substantial starch content (26.36-63.29%) and relatively low cellulose contents (7.85-21.02%). Due to their high starch content, the combined action of cellulolytic and amylolytic enzymes resulted in greater release of glucose from the raw HBRs compared to using the individual enzyme alone. Batch enzymatic hydrolysis of 10% (w/v) raw HBRs with low loadings of cellulase (≤ 10 FPU/g substrate) and amylolytic enzymes (≤ 5.0 mg/g substrate) led to a high glucan conversion of ≥ 70%. The addition of PEG 6000 and Tween 20 did not contribute to glucose production. Furthermore, to achieve higher glucose concentrations, fed-batch enzymatic hydrolysis was conducted using a total solid loading of 30% (w/v). After 48-h of hydrolysis, glucose concentrations of 125 g/L and 92 g/L were obtained for IR and SFR residues, respectively. GR residue yielded an 83 g/L glucose concentration after 96 h of digestion. The high glucose concentrations produced from these raw HBRs indicate their potential as ideal substrate for a profitable biorefinery. Notably, the obvious advantage of using these HBRs is the elimination of the pretreatment step, which is typically required for agricultural and woody biomass in similar studies.

C-reactive Protein/Albumin Ratio as a Prognostic Indicator in Posttraumatic Shock and Outcome of Multiple Trauma Patients.

OBJECTIVE: C-reactive protein (CRP)/albumin ratio (CAR) is a new inflammation-based index for predicting the prognosis of various diseases. The CAR determined on admission may help to predict the prognostic value of multiple trauma patients. METHODS: A total of 264 adult patients with severe multiple trauma were included for the present retrospective study, together with the collection of relevant clinical and laboratory data. CAR, CRP, albumin, shock index and ISS were incorporated into the prognostic model, and the receiver operating characteristic (ROC) curve was drawn. Then, the shock index for patients with different levels of CAR was analyzed. Finally, univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for the 28-day mortality of multiple trauma patients. RESULTS: A total of 36 patients had poor survival outcomes, and the mortality rate reached 13.6%. Furthermore, after analyzing the shock index for patients with different levels of CAR, it was revealed that the shock index was significantly higher when CAR was ≥4, when compared to CAR <2 and 2≤ CAR <4, in multiple trauma patients. The multivariate logistic analysis helped to identify the independent association between the variables CAR (P=0.029) and shock index (P=0.019), and the 28-day mortality of multiple trauma patients. CONCLUSION: CAR is higher in patients with severe multiple trauma. Furthermore, CAR serves as a risk factor for independently predicting the 28-day mortality of multiple trauma patients. The shock index was significantly higher when CAR was ≥4 in multiple trauma patients.

Highly efficient glucose production from raw non-pretreated Chinese medicinal herbal residues via the synergism of cellulase and amylolytic enzymes.

Available literature on Chinese medicinal herbal residues (CMHRs) bioconversion highlights pretreatment prior to saccharification with cellulase without considering the presence of starch constituent. Herein, four commonly found CMHRs were tested for starch content, and it was found they all contained starch with content ranging from 4.74% to 16.78%. Hydrolysis of raw CMHRs with combined cellulase and amylolytic enzymes yielded increments of 16.85% to 26.51% in 48-h glucan conversion compared to cellulase alone. Further study showed 48-h glucan conversion of raw CMHRs outperformed that pretreated by water-ethanol successive extraction, ultrasound and acid, but underperformed alkali-pretreated CMHRs. Although increasing 48-h glucan conversion in the range of 7.40% to 24.10% compared to raw CMHRs, alkaline pretreatment demonstrated low glucose recovery and incurred additional cost, making it unfavorable. Saccharification of the four raw CMHRs with combined enzymes seems like a preferred option considering the elimination of high-cost pretreatment step.

Optimizing the SERS Performance of 3D Substrates through Tunable 3D Plasmonic Coupling toward Label-Free Liver Cancer Cell Classification.

Three-dimensional (3D) plasmonic nanostructures are emerging as excellent surface-enhanced Raman spectroscopy (SERS) substrates for chemical and biomedical applications. However, the correlation of 3D (including both in-plane and out-of-plane) plasmonic coupling with the SERS properties to deepen the understanding of 3D SERS substrates remains a challenge. Here, we perform correlation studies of 3D plasmonic coupling and SERS properties of the 3D hierarchical SERS substrates by tuning the multiscale structural elements. The effects of zero-dimensional (0D; the size of the building blocks), one-dimensional (1D; the thickness of the 3D substrates), and two-dimensional (2D; the composition of individual monolayers) structural elements on 3D plasmonic coupling are studied by performing UV-vis-near-infrared (NIR) spectroscopy and measuring SERS performance. It shows that both the extinction spectra and SERS enhancement are tuned at the 3D structural level. It is demonstrated that the plasmonic resonance wavelength (PRW) stemming from the 3D plasmonic coupling correlates with the SERS averaged surface enhancement factor (ASEF) and is improved by more than tenfold at the optimum 3D nanostructure. The optimized substrate is used to quantitatively analyze two small biological molecules. Moreover, as a proof-of-concept study, the substrate is first applied to differentiate between living liver normal and cancer cells with a high prediction accuracy through the spectral features of the cell membranes and the metabolites secreted outside the cells. We expect that the tuning of plasmonic coupling at the 3D level can open up new routes to design high-performance SERS substrates for wide applications.

FVIIa prevents the progressive hemorrhaging of a brain contusion by protecting microvessels via formation of the TF-FVIIa-FXa complex.

Factor VII (FVII) plays a key role in the initiation of the coagulation cascade and, in clinical situations, recombinant human activated FVII (rFVIIa) effectively prevents progressive hemorrhaging after a brain contusion. However, it remains unclear whether decreases in FVII activity directly lead to progressive hemorrhaging and, moreover, the precise mechanisms underlying this process are not yet known. The present study demonstrated that decreased FVII activity directly led to progressive hemorrhaging of the cerebral contusions. Administration of FVII prevented the progression of hemorrhaging from cerebral contusions by protecting microvessel endothelial cells in the penumbra of the contusion. The present study also showed that the ternary TF-FVIIa-FXa complex cleaved endogenous protease-activated receptor 2 (PAR2) on endothelial cells, activated the p44/42 mitogen-activated protein kinase (MAPK) signaling cascade, and inhibited p65 nuclear factor-κB (NF-κB) signaling. Furthermore, exposure to ternary TF-FVIIa-FXa protected endothelial cells from thrombin- or inflammatory cytokine-induced apoptosis. Although activation of the p44/42 MAPK signaling pathway is endothelial cell protein C receptor (EPCR)-dependent, inhibition of the p65 NF-κB signaling pathway is EPCR-independent; thus, the regulation mechanism underlying the effects of TF-FVIIa-FXa in vascular endothelial cells appears to be multiple signaling pathways. In summary, the present findings demonstrated that FVIIa prevented the progressive hemorrhaging of brain contusions by protecting microvessel endothelial cells via the formation of the ternary TF-FVIIa-FXa complex. These findings are novel and of great clinical significance because FVIIa is used to prevent the progressive hemorrhaging of brain contusions in humans.

Is Intracranial Pressure Monitoring of Patients With Diffuse Traumatic Brain Injury Valuable? An Observational Multicenter Study.

BACKGROUND: Although intracranial pressure (ICP) monitoring of patients with severe traumatic brain injury (TBI) is recommended by the Brain Trauma Foundation, any benefits remain controversial. OBJECTIVE: To evaluate the effects of ICP monitoring on the mortality of and functional outcomes in patients with severe diffuse TBI. METHODS: Data were collected on patients with severe diffuse TBI (Glasgow Coma Scale [GCS] score on admission <9 and Marshall Class II-IV) treated from January 2012 to December 2013 in 24 hospitals (17 level I trauma centers and 7 level II trauma centers) in 9 Chinese provinces. We evaluated the impact of ICP monitoring on 6-month mortality and favorable outcome using propensity score-matched analysis after controlling for independent predictors of these outcomes. RESULTS: ICP monitors were inserted into 287 patients (59.5%). After propensity score matching, ICP monitoring significantly decreased 6-month mortality. ICP monitoring also had a greater impact on the most severely injured patients on the basis of head computed tomography data (Marshall computed tomography classification IV) and on patients with the lowest level of consciousness (GCS scores 3-5). After propensity score matching, monitoring remained nonassociated with a 6-month favorable outcome for the overall sample. However, monitoring had a significant impact on the 6-month favorable outcomes of patients with the lowest level of consciousness (GCS scores 3-5). CONCLUSION: ICP monitor placement was associated with a significant decrease in 6-month mortality after adjustment for the baseline risk profile and the monitoring propensity of patients with diffuse severe TBI, especially those with GCS scores of 3 to 5 or of Marshall computed tomography classification IV.

Prevalence of severe hypokalaemia in patients with traumatic brain injury.

INTRODUCTION: Patients with traumatic brain injury (TBI) are more vulnerable to develop hypokalaemia, we sought to investigate the prevalence, and the relationship between severe hypokalaemia and the mortality of traumatic brain injury patients. METHODS: Isolated traumatic brain patients who had hypokalaemia (serum potassium <3.5mmol/L) and age≥14yrs were recruited into the study between January 2008 and March 2013. Hypokalaemia was defined as potassium level in the blood <3.5mmol/L during the hospitalisation, which was classified by severity: mild (3.0mmol/L≤K<3.5mmol/L), moderate (2.5mmol/L≤K<3.0mmol/L) and severe (K<2.5mmol/L). Multivariable logistic regression was performed to find the impact of hypokalaemia on mortality. RESULTS: A total 375 cases were included in analysis. The peak incidence of severe hypokalaemia occurred in the first 24-96h. TBI patients with severe hypokalaemia had significantly higher serum sodium and lower serum phosphorus than those patients with mild or moderate hypokalaemia (p<0.001). Compare to other groups, the severe hypokalaemia group had the worst outcome. Moreover, the patients (n=15) who had severe hypokalaemia, hypernatraemia (Na>160mmol/L), and hypophosphataemia (P<0.3mmol/L) all died in hospital. Multiple logistic regression analysis resulted in decrease of GCS (OR=1.27; 95% CI=1.15-1.41; p<0.001) and potassium (OR=4.35; 95% CI=2.04-9.26; p<0.001) being associated with significant increased risk of mortality. CONCLUSIONS: The peak incidence of severe hypokalaemia occurred in the first 24-96h. TBI patients with severe hypokalaemia are more vulnerable to develop hypophosphataemia and hypernatraemia than patients with mild and moderate hypokalaemia. Severe hypokalaemia are the independent risk factors for mortality in TBI patients.

Examination of the relationship between chromosome abnormality in pituitary adenomas and tumor invasiveness by normal karyotype analysis and interphase fluorescence staining.

To study the potential relationship between chromosome abnormality and tumor invasiveness in pituitary adenomas. To use conventional R-band cytogenetic karyotype analysis and interphase fluorescence in situ hybridization using centromeric probe of chromosomes 8, 9, and 11 to detect chromosome abnormality in 30 cases of pituitary adenoma. All chromosomes except chromosomes 4, 16, and Y show significant variation between invasive and noninvasive pituitary adenomas. Chromosomes 8 and 12 display some type of numeric alteration in all endocrine subtypes of pituitary adenoma. Numeric alterations in chromosomes 9, 11, and 19 are more frequently detected in invasive pituitary adenomas compared with noninvasive tumors. Numeric alterations in chromosomes are common in all endocrine subtype pituitary adenomas. Furthermore, chromosome numbers are significantly different in invasive and noninvasive pituitary adenomas. On the basis of our study and literature review, we conclude that while chromosomes 8 and 12 may play important roles in the occurrence of pituitary adenomas, chromosomes 9, 11, and 19 may be specifically associated with invasiveness.

[Preliminary study of p16 gene expression in pituitary adenomas].

BACKGROUND & OBJECTIVE: The inactivation and low expression of tumor suppressor gene p16 has been found to play an important role in the tumorigenesis of a wide variety of human tumors, but its association with human pituitary adenomas was not clear. This study was conducted to investigate the relationship between p16 gene expression and clinicopathologic features including invasiveness and recurrence in pituitary adenoma patients. METHODS: The p16 mRNA and p16 protein expression levels were examined using reverse transcription polymerase chain reaction (RT-PCR) and Western Blot analysis respectively in 70 pituitary adenomas and 10 normal brain tissues. RESULTS: Fifty-two of 70 (74.3%) tumor samples presented loss or low p16 mRNA and p16 protein. The invasive and recurrent adenomas had higher loss expression rates than noninvasive and nonrecurrent group respectively; however, there was no significant difference (P >0.05). Moreover, the mean diameter of adenomas without p16 expression was obviously larger than that of p16-positive tumors (22.1+/-7.2 mm versus 8.1+/-4.5 mm, P< 0.01). There was no association between p16 expression and other clinicopathologic features of pituitary adenomas. CONCLUSION: These findings suggested that p16 down-regulation may play an important role in the initial tumorigenesis, growth, and biological behavior of pituitary adenomas.

[Preliminary study of chromosome aberrations in pituitary adenoma].

BACKGROUND & OBJECTIVE: Pituitary adenoma is one of the most common intracranial benign tumor. This study was designed to seek the most suitable method for cytogenetic study of pituitary adenoma(PA), and then to analyze the genetic change of PA cell. METHODS: Twenty-five samples of primary PA were examined by R-banding through direct preparation(DP) and short-term culture(STC) to analyze genomic alterations. RESULTS: A karyotype of 17 samples was identified in 25 PAs by using the DP, whereas there was a karyotype of 21 samples by using the STC. An abnormal clonal karyotype was observed in 11 samples processed by the DP, however only 3 of 25 samples when processed by the STC. The common chromosomal alterations included gains of chromosomes X(6/25), 7(4/25), 8(2/25), 5(2/25) as well as losses of chromosomes 11(5/25), 9(4/25), 13(3/25), and the latter was observed predominantly in invasive PAs. CONCLUSIONS: DP is one of the most suitable methods for the cytogenetic study of PA. There were multiple regions of chromosomes with copy number changes in PA including gains of chromosomes X, 7, 8, and losses of chromosomes 11, 9, 13. However, structural chromosome aberrations are not common. The loss of chromosome and the abnormality of structure may have some correlation with the biologic behavior of PA.