Effect of neutrophil to lymphocyte ratio on prognosis of elderly patients with severe sepsis combined with diabetes mellitus.

BACKGROUND: To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) in the short-term prognosis of elderly patients with severe sepsis combined with diabetes mellitus (DM). METHODS: The clinical data of 162 elderly patients with severe sepsis combined with DM from January 2018 to December 2022 were retrospectively collected. These patients were divided into a survival group (n = 104) and a death group (n = 58) according to 90-day prognosis. The number of neutrophils, lymphocytes, and NLR were compared. The optimal cut-off value for NLR to predict 90-day prognosis in elderly patients with severe sepsis combined with DM was determined using Receiver Operator Characteristic (ROC) curves, and the patients were divided into high and low NLR groups depending on the optimal cut-off value. The Kaplan-Meier method was used to plot the survival curves of the high and low NLR groups. Risk factors for the 90-day death in elderly patients with severe sepsis combined with DM were analyzed by a multivariate cox regression model. RESULTS: There were no significant differences in gender, age, history of hypertension and hyperlipidemia, intensive care unit (ICU) stay, duration of mechanical ventilation, and oxygenation index between the survival group and death group (p > 0.05). However, acute physiological and chronic health evaluation II (APACHE II) scores, and sepsis-related organ failure assessment (SOFA) scores were significantly lower in the survival group compared with the death group (p < 0.05). In the survival group, neutrophils counts and NLR were much lower than those in the death group, while lymphocytes counts were much higher (p < 0.05). ROC curves showed that the optimal cut-off value for NLR to predict 90-day mortality in elderly patients with severe sepsis combined with DM was 3.482. Patients were divided into high NLR and low NLR groups based on whether NLR was ≥ 3.482. In terms of the log-rank test results, patients in the low NLR group had a significantly higher 90-day survival rate than those in the high NLR group (Logrank χ2 = 8.635, p = 0.003). The multivariate cox regression model showed that the length of ICU stay longer than 15 days and NLR ≥ 3.482 were independent risk factors for 90-day prognosis in elderly patients with severe sepsis combined with DM. CONCLUSION: NLR ≥ 3.482 can be used to predict whether poor prognosis occurs in the short term after illness in elderly patients with severe sepsis combined with DM, and has good assessment value.

Population pharmacokinetic models of lamotrigine in different age groups of Chinese children with epilepsy.

PURPOSE: The study aims to establish population pharmacokinetic (PPK) models of lamotrigine (LTG) in different age groups of epileptic children by nonlinear mixed effect modelling(NONMEM), and provide essential tools and theoretical basis for individualised optimal drug dose. METHODS: Cases of 473 epileptic children were divided into infant, toddler and preschool age (≤6 years) (n = 211), school age (6-12 years) (n = 171) and adolescence age (>12 years) (n = 81). A total of 625 steady-state serum trough concentration samples were extracted. The clinical information included demography, medication, serum concentration data and blood biochemical parameters. PPK models of LTG were established by NONMEM program, using first-order absorption and elimination. Demography and drug combination was investigated for influence on apparent clearance (CL) and apparent volume of distribution (Vd). To assess the accuracy and precision of the different ages and whole-age model, the mean prediction error (MPE), mean absolute error (MAE) and root mean squared error (RMSE) were compared. RESULTS: The final model of LTG in different ages stage and whole age was as follows: (1) infant, toddler and preschool age CL = 0.715 × [(WEIG/16.25)0.655] × (0.458VPA) × (1.99IND), V = 10.4; (2) school age CL(L/h) = 1.01 × (WEIG/30)0.399 × 0.465VPA × 1.98IND, Vd(L) = 17.7; (3) adolescence age CL(L/h) = 1.49 × (WEIG/51.5)0.509 × 0.498VPA × 1.7IND, Vd(L) = 23.1; (4) whole age CL = 0.945 × [(WEIG/25)0.645] × (0.463VPA) × (1.94IND), V = 16.7 × (WEIG/25)0.919 (WEIG, total body weight; VPA, combination with valproate, yes = 1, no = 0; IND, combination with enzyme inducer, yes = 1, no = 0). The values of MPE, MAE and RMSE in age-stage-specific models were less than the ones in the whole-age model, which suggests the age-stage-specific models have better precision and accuracy than the whole-age model. CONCLUSION: PPK models of LTG in different age groups of epileptic children were successfully established. Weight and combination therapy were identified as significant covariates on LTG clearance. Compared with the whole-age model, the age-specific models are more reliable.

Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder.

BACKGROUND: We aimed to investigate the disruptions of functional connectivity of amygdala-based networks in adolescents with untreated generalized anxiety disorder (GAD). MATERIAL AND METHODS: A total of 26 adolescents with first-episode GAD and 20 normal age-matched volunteers underwent resting-state and T1 functional magnetic resonance imaging (fMRI). We analyzed the correlation of fMRI signal fluctuation between the amygdala and other brain regions. The variation of amygdala-based functional connectivity and its correlation with anxiety severity were investigated. RESULTS: Decreased functional connectivity was found between the left amygdala and left dorsolateral prefrontal cortex. An increased right amygdala functional connectivity with right posterior and anterior lobes of the cerebellum, insula, superior temporal gyrus, putamen, and right amygdala were found in our study. Negative correlations between GAD scores and functional connectivity of the right amygdala with the cerebellum were also observed in the GAD adolescents. CONCLUSIONS: Adolescents with GAD have abnormalities in brain regions associated with the emotional processing pathways.

Quantitative radiomics analysis of imaging features in adults and children Mycoplasma pneumonia.

Purpose: This study aims to explore the value of clinical features, CT imaging signs, and radiomics features in differentiating between adults and children with Mycoplasma pneumonia and seeking quantitative radiomic representations of CT imaging signs. Materials and methods: In a retrospective analysis of 981 cases of mycoplasmal pneumonia patients from November 2021 to December 2023, 590 internal data (adults:450, children: 140) randomly divided into a training set and a validation set with an 8:2 ratio and 391 external test data (adults:121; children:270) were included. Using univariate analysis, CT imaging signs and clinical features with significant differences (p < 0.05) were selected. After segmenting the lesion area on the CT image as the region of interest, 1,904 radiomic features were extracted. Then, Pearson correlation analysis (PCC) and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomic features. Based on the selected features, multivariable logistic regression analysis was used to establish the clinical model, CT image model, radiomic model, and combined model. The predictive performance of each model was evaluated using ROC curves, AUC, sensitivity, specificity, accuracy, and precision. The AUC between each model was compared using the Delong test. Importantly, the radiomics features and quantitative and qualitative CT image features were analyzed using Pearson correlation analysis and analysis of variance, respectively. Results: For the individual model, the radiomics model, which was built using 45 selected features, achieved the highest AUCs in the training set, validation set, and external test set, which were 0.995 (0.992, 0.998), 0.952 (0.921, 0.978), and 0.969 (0.953, 0.982), respectively. In all models, the combined model achieved the highest AUCs, which were 0.996 (0.993, 0.998), 0.972 (0.942, 0.995), and 0.986 (0.976, 0.993) in the training set, validation set, and test set, respectively. In addition, we selected 11 radiomics features and CT image features with a correlation coefficient r greater than 0.35. Conclusion: The combined model has good diagnostic performance for differentiating between adults and children with mycoplasmal pneumonia, and different CT imaging signs are quantitatively represented by radiomics.

Predicting the severity of mycoplasma pneumoniae pneumonia in pediatric and adult patients: a multicenter study.

The purpose of this study is to develop a nomogram model for early prediction of the severe mycoplasma pneumoniae pneumonia (SMPP) in Pediatric and Adult Patients. A retrospective analysis was conducted on patients with MPP, classifying them into SMPP and non-severe MPP (NSMPP) groups. A total of 550 patients (NSMPP 374 and SMPP 176) were enrolled in the study and allocated to training, validation cohorts. 278 patients (NSMPP 224 and SMPP 54) were retrospectively collected from two institutions and allocated to testing cohort. The risk factors for SMPP were identified using univariate analysis. For radiomic feature selection, Spearman's correlation and the least absolute shrinkage and selection operator (LASSO) were utilized. Logistic regression was used to build different models, including clinical, imaging, radiomics, and integrated models (combining clinical, imaging, and radiomics features selected). The model's discrimination was evaluated using a receiver operating characteristic curve, its calibration with a calibration curve, and the results were visualized using the Hosmer-Lemeshow goodness-of-fit test. Thirteen clinical features and fourteen imaging features were selected for constructing the clinical and imaging models. Simultaneously, a set of twenty-five radiomics features were utilized to build the radiomics model. The integrated model demonstrated good calibration and discrimination in the training cohorts (AUC, 0.922; 95% CI: 0.900, 0.942), validation cohorts (AUC, 0.879; 95% CI: 0.806, 0.920), and testing cohorts (AUC, 0.877; 95% CI: 0.836, 0.916). The discriminatory and predictive efficacy of the clinical model in testing cohorts increased further after clinical and radiological features were incorporated (AUC, 0.849 vs. 0.922, P = 0.002). The model demonstrated exemplary predictive efficacy for SMPP by leveraging a comprehensive set of inputs, encompassing clinical data, quantitative and qualitative radiological features, along with radiomics features. The integration of these three aspects in the predictive model further enhanced the performance of the clinical model, indicating the potential for extensive clinical applications.

The in vitro effects of gibberellin on human sperm motility.

Gibberellin, a plant growth regulator, is widely used to increase the shelf life and quality of fruits and vegetables. In this study, human semen samples were exposed to different concentrations of gibberellin, which reduced spermatozoa motility in vitro. Gibberellin exposure also increased levels of reactive oxygen species and the protein levels of apoptosis markers in human sperm. Gibberellin inhibited the activity of Na+/K+-adenosine triphosphatase (ATPase) and Ca2+-ATPase, which maintain the stability of ions inside and outside the membranes of spermatozoa. Moreover, gibberellin exposure suppressed adenosine triphosphate production and reduced the protein levels of adenosine triphosphate synthases, which may have induced the protein expression of adenosine 5'-monophosphate-activated protein kinase (AMPK) and its phosphorylated form. These results suggest that gibberellin reduces human sperm motility in vitro by increasing reactive oxygen species levels and reducing ATPase activity, which may upregulate AMPK and consequently reduce the fertilization potential of spermatozoa.

Research progress of ursolic acid's anti-tumor actions.

Ursolic acid (UA) is a sort of pentacyclic triterpenoid carboxylic acid purified from natural plant. UA has a series of biological effects such as sedative, anti-inflammatory, anti-bacterial, anti-diabetic, antiulcer, etc. It is discovered that UA has a broad-spectrum anti-tumor effect in recent years, which has attracted more and more scholars' attention. This review explained anti-tumor actions of UA, including (1) the protection of cells' DNA from different damages; (2) the anti-tumor cell proliferation by the inhibition of epidermal growth factor receptor/mitogen-activated protein kinase signal or of FoxM1 transcription factors, respectively; (3) antiangiogenesis, (4) the immunological surveillance to tumors; (5) the inhibition of tumor cell migration and invasion; (6) the effect of UA on caspase, cytochromes C, nuclear factor kappa B, cyclooxygenase, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or mammalian target of rapamycin signal to induce tumor cell apoptosis respectively, and etc. Moreover, UA has selective toxicity to tumor cells, basically no effect on normal cells. With further studies, UA would be one of the potential anti-tumor agents.

[Clinical and genetic study of twelve Chinese patients with Alexander disease].

OBJECTIVE: To delineate the phenotype and genotype characteristics in 12 Chinese children with Alexander disease (AD), which is helpful for the molecular diagnosis and genetic counseling in China. METHODS: Clinical diagnosis of AD was based on MRI criteria proposed by van der Knaarp in 2001. Included AD patients were followed up for 0.50 - 3.67 years. Mutations in GFAP were detected by DNA sequencing. RESULTS: The 12 cases of AD were clinically diagnosed. Age of first visit was 4.87 years (0.75 - 12.00 years), with 3 types of chief complaints: developmental delay in 3, recurrent seizures in 7, unable to walk after falling in 2. Average head circumference was 52.34 cm (44 - 58 cm), which larger than age-matched average by 6.45% (1.80% - 13.95%). On the first visit, scaling according to Gross motor functional classification system (GMFCS) was performed, with GMFCSI in 8, II in 3, V in 1. Mild to severe cognitive dysfunction were found in 8, and seizures in 11 cases. The 12 patients were followed up for 0.50 - 3.67 years, their motor and cognitive function remained stable. Episodic aggravations provoked by fever or falling were observed in 5 cases (41.67%). Heterozygous missense mutations of GFAP were detected in 12 patients. All mutations were de novo; 3 out of 10 mutations identified were novel. R79 and R239 were hot mutations, which was consistent with previous reports. Mutations were located in exon 1 in 8 cases. CONCLUSIONS: The phenotype in these patients is characterized by slower progression compared with reports from other population and high incidence of seizures. And episodic aggravations provoked by fever or falling were more common. The genotype characteristics are consistent with previous reports. The results of this research expanded the number of patients with Alexander disease found to have GFAP coding mutations in China.

Analysis of 142 genes resolves the rapid diversification of the rice genus.

BACKGROUND: The completion of rice genome sequencing has made rice and its wild relatives an attractive system for biological studies. Despite great efforts, phylogenetic relationships among genome types and species in the rice genus have not been fully resolved. To take full advantage of rice genome resources for biological research and rice breeding, we will benefit from the availability of a robust phylogeny of the rice genus. RESULTS: Through screening rice genome sequences, we sampled and sequenced 142 single-copy genes to clarify the relationships among all diploid genome types of the rice genus. The analysis identified two short internal branches around which most previous phylogenetic inconsistency emerged. These represent two episodes of rapid speciation that occurred approximately 5 and 10 million years ago (Mya) and gave rise to almost the entire diversity of the genus. The known chromosomal distribution of the sampled genes allowed the documentation of whole-genome sorting of ancestral alleles during the rapid speciation, which was responsible primarily for extensive incongruence between gene phylogenies and persisting phylogenetic ambiguity in the genus. Random sample analysis showed that 120 genes with an average length of 874 bp were needed to resolve both short branches with 95% confidence. CONCLUSION: Our phylogenomic analysis successfully resolved the phylogeny of rice genome types, which lays a solid foundation for comparative and functional genomic studies of rice and its relatives. This study also highlights that organismal genomes might be mosaics of conflicting genealogies because of rapid speciation and demonstrates the power of phylogenomics in the reconstruction of rapid diversification.