[Changes and significance of oxidized phospholipids and endothelial nitric oxide synthase in the acute stage of Kawasaki disease]. / å·å´Žç— æ€¥æ€§æœŸæ°§åŒ–ç£·è„‚å’Œå† çš®ä¸€æ°§åŒ–æ°®åˆé ¶çš„å˜åŒ–åŠæ„ä¹‰.

OBJECTIVES: To investigate the changes in the serum levels of oxidized phospholipids (OxPLs) and endothelial nitric oxide synthase (eNOS) and their association with coronary artery disease (CAL) in children in the acute stage of Kawasaki disease (KD), as well as the clinical significance of OxPLs and eNOS. METHODS: A prospective study was conducted on 95 children in the acute stage of KD (KD group). According to the presence of absence of CAL, the KD group was further divided into a CAL subgroup and a non-CAL (NCAL) subgroup. Thirty children with fever due to lower respiratory tract infection were enrolled as the fever group. Thirty healthy children who underwent physical examination were enrolled as the healthy control group. The above groups were compared in terms of general information and serum levels of OxPLs, eNOS and other laboratory indexes, and the correlation between OxPLs level and eNOS level was analyzed. RESULTS: The KD group had a significantly higher level of OxPLs and a significantly lower level of eNOS compared with the fever group and the healthy control group (P<0.05). After treatment, the children with KD had a significantly decreased OxPLs level and a significantly increased eNOS level (P<0.05). Compared with the NCAL subgroup, the CAL subgroup had a significantly higher level of OxPLs and a significantly lower level of eNOS (P<0.05). Among the children of KD, the level of OxPLs was negatively correlated with that of eNOS (rs=-0.353, P<0.05). CONCLUSIONS: Serum OxPLs and eNOS in the acute stage of KD may be involved in the development of CAL in children with KD, and therefore, they may be used as the biomarkers to predict CAL in these children.

Exploring blood transcriptomic signatures in patients with herpes zoster and postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN is developed from herpes zoster (HZ), the developing mechanism is unknown. A previous study investigated blood metabolomic and proteomic profiling in patients with PHN and HZ. The current study aims to explore the blood transcriptomic signature of PHN compared to HZ patients. Whole blood from eight PHN and 15 HZ patients was used for RNA-Seq analysis. There were 82 and 1,788 genes detected specifically in the PHN and HZ groups, respectively. PHN-specific genes are involved in viral infection, lipid and carbohydrate metabolism, and immune response. For genes coexpressed in PHN and HZ patients, there were 407 differential expression genes (DEGs), including 205 upregulated (UP DEGs) and 202 downregulated (DOWN DEGs) in PHN compared to HZ groups. DEGs are involved in viral infection, type I interferon (IFN), and hemoglobin and oxygen carrier activity. UP DEGs are associated with regulatory T cells (Tregs), activated NK cells, and neutrophils, while DOWN DEGs are associated with Tregs, resting NK cells, and monocytes. The results suggest that the metabolism of lipid, glycan, and nucleotides, type I IFN signaling, and altered neutrophil activation are associated with and might contribute to the development of PHN in HZ. It is also suggested that persistent or altered activation of nonspecific immunity may contribute to the development of PHN from HZ.

[Effect and safety of pulsatile GnRH therapy for male congenital hypogonadotropic hypogonadism].

OBJECTIVE: To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congenital hypogonadotropic hypogonadism (CHH). METHODS: We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023. We treated the patients with gonadorelin at 7－15 µg, one pulse/90 min, and followed them up every month in the first 3 months and then every 3 to 6 months after treatment, for an average of 19.1±4.3 months, during which we recorded the height, body weight, penile length, testis volume, Tanner stages, levels of FSH, LH and T, semen parameters and adverse reactions of the patients, followed by comparison of the data obtained with the baseline. RESULTS: The levels of FSH, LH and T of the patients were dramatically elevated after treatment (P < 0.01). The T level of the 6 cases of cryptorchidism, however, failed to reach the normal value within 18.2 ± 8.6 months of follow-up. Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients, and spermatogenesis was observed in the semen in 33 cases (73.3%), with a mean sperm concentration of (18.2 ± 6.2) 106/ml, sperm progressive motility of (19.7 ± 6.5) %, and semen volume of (1.8 ± 0.6) ml. Eight of the cases achieved natural fertility, and another 3 achieved childbirth by assisted reproductive technology. As for adverse events, gynecomastia was observed in 8, subcutaneous induration in 6, and allergic reaction to therapeutic agent in 3 cases. CONCLUSION: Pulsatile GnRH therapy is an effective and safe strategy for male CHH. However, clinicians should choose appropriate approaches to different individual cases.

Plastome evolution of Engelhardia facilitates phylogeny of Juglandaceae.

BACKGROUND: Engelhardia (Juglandaceae) is a genus of significant ecological and economic importance, prevalent in the tropics and subtropics of East Asia. Although previous efforts based on multiple molecular markers providing profound insights into species delimitation and phylogeography of Engelhardia, the maternal genome evolution and phylogeny of Engelhardia in Juglandaceae still need to be comprehensively evaluated. In this study, we sequenced plastomes from 14 samples of eight Engelhardia species and the outgroup Rhoiptelea chiliantha, and incorporated published data from 36 Juglandaceae and six outgroup species to test phylogenetic resolution. Moreover, comparative analyses of the plastomes were conducted to investigate the plastomes evolution of Engelhardia and the whole Juglandaceae family. RESULTS: The 13 Engelhardia plastomes were highly similar in genome size, gene content, and order. They exhibited a typical quadripartite structure, with lengths from 161,069 bp to 162,336 bp. Three mutation hotspot regions (TrnK-rps16, ndhF-rpl32, and ycf1) could be used as effective molecular markers for further phylogenetic analyses and species identification. Insertion and deletion (InDels) may be an important driving factor for the evolution of plastomes in Juglandoideae and Engelhardioideae. A total of ten codons were identified as the optimal codons in Juglandaceae. The mutation pressure mostly contributed to shaping codon usage. Seventy-eight protein-coding genes in Juglandaceae experienced relaxed purifying selection, only rpl22 and psaI genes showed positive selection (Ka/Ks > 1). Phylogenetic results fully supported Engelhardia as a monophyletic group including two sects and the division of Juglandaceae into three subfamilies. The Engelhardia originated in the Late Cretaceous and diversified in the Late Eocene, and Juglandaceae originated in the Early Cretaceous and differentiated in Middle Cretaceous. The phylogeny and divergence times didn't support rapid radiation occurred in the evolution history of Engelhardia. CONCLUSION: Our study fully supported the taxonomic treatment of at the section for Engelhardia species and three subfamilies for Juglandaceae and confirmed the power of phylogenetic resolution using plastome sequences. Moreover, our results also laid the foundation for further studying the course, tempo and mode of plastome evolution of Engelhardia and the whole Juglandaceae family.

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations.

PURPOSE: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. METHODS: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. RESULTS: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. CONCLUSION: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

[Anti-inflammatory effect and its mechanism of Saracae Cortex based on zebrafish model and network pharmacology].

This paper aims to explore the anti-inflammatory mechanism of Saracae Cortex by using network pharmacology and molecular docking methods and verify it through the inflammation model of zebrafish. The effective components, potential core targets, and signaling pathways of Saracae Cortex were obtained by using network pharmacology. A lipopolysaccharide(LPS)-induced inflammation model of zebrafish was established to evaluate the anti-inflammatory activity of aqueous extract and 70% ethanol extract of Saracae Cortex with cell apoptosis rate and reactive oxygen species(ROS) production rate as indicators. q PCR was performed to verify the main targets predicted by network pharmacology. The prediction found that there were 121 potential anti-inflammatory targets in Saracae Cortex. Protein-protein interaction(PPI) analysis showed that Saracae Cortex mainly acted on signal transducer and activator of transcription 3(STAT3), vascular endothelial growth factor A( VEGFA), epidermal growth factor( EGF), tumor necrosis factor( TNF),tumor protein p53(TP53), matrix metalloprotein 9(MMP9), c-fos proto-oncogene protein(FOS), estrogen receptor 1(ESR1), cx-c motif chemokine ligand 8(CXCL8), cluster of differentiation 8(CD8), and other targets. Gene Ontology(GO) analysis showed the biological process mainly acted on the inhibition of apoptosis, the positive regulation of gene expression, and the positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the mitogen-activated protein kinase(MAPK) signaling pathway, PI3K-Akt signaling pathway, and hypoxia-inducible factor 1(HIF-1) signaling pathway may play a key role in anti-inflammation of Saracae Cortex. Molecular docking verified that five key compounds had a strong binding force with their corresponding core target. Zebrafish animal experiments showed that Saracae Cortex could significantly inhibit ROS formation and reduce cell apoptosis in juvenile fish caused by inflammation and inhibit the further enhancement of inflammatory response in tissue. In addition, compared with the blank group, the transcription levels of nuclear factor kappa-B(NF-κB), TP53, FOS, adaptor protein complex-1(AP-1), and mitogen-activated protein kinases P38(P38) were significantly up-regulated in the model group. Compared with the model group, the m RNA expression of NF-κB, TP53, FOS, AP-1, and P38 was significantly down-regulated in zebrafish tissue treated with aqueous extract and 70% ethanol extract of Saracae Cortex. Saracae Cortex plays an anti-inflammatory role through multiple components and targets, and its anti-inflammatory effect may be related to the inhibition of the MAPK signaling pathway.

Radiomics-Based Prediction of Microvascular Invasion Grade in Nodular Hepatocellular Carcinoma Using Contrast-Enhanced Magnetic Resonance Imaging.

Objective: The aim of this study is to develop and verify a magnetic resonance imaging (MRI)-based radiomics model for predicting the microvascular invasion grade (MVI) before surgery in individuals diagnosed with nodular hepatocellular carcinoma (HCC). Methods: A total of 198 patients were included in the study and were randomly stratified into two groups: a training group consisting of 139 patients and a test group comprising 59 patients. The tumor lesion was manually segmented on the largest cross-sectional slice using ITK SNAP, with agreement reached between two radiologists. The selection of radiomics features was carried out using the LASSO (Least Absolute Shrinkage and Selection Operator) algorithm. Radiomics models were then developed through maximum correlation, minimum redundancy, and logistic regression analyses. The performance of the models in predicting MVI grade was assessed using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix. Results: There were no notable statistical differences in sex, age, BMI (body mass index), tumor size, and location between the training and test groups. The AP and PP radiomic model constructed for predicting MVI grade demonstrated an AUC of 0.83 (0.75-0.88) and 0.73 (0.64-0.80) in the training group and an AUC of 0.74 (0.61-0.85) and 0.62 (0.48-0.74) in test group, respectively. The combined model consists of imaging data and clinical data (age and AFP), achieved an AUC of 0.85 (0.78-0.91) and 0.77 (0.64-0.87) in the training and test groups, respectively. Conclusion: A radiomics model utilizing-contrast-enhanced MRI demonstrates strong predictive capability for differentiating MVI grades in individuals with nodular HCC. This model could potentially function as a dependable and resilient tool to support hepatologists and radiologists in their preoperative decision-making processes.

Support for banning sale of smoked tobacco products among adults who smoke: findings from the International Tobacco Control Four Country Smoking and Vaping Surveys (2018-2022).

BACKGROUND: Many people continue to smoke despite strong policies to deter use, thus stronger regulatory measures may be required. In four high-income countries, we examined whether people who smoke would support a total ban on smoked tobacco products under two differing policy scenarios. METHODS: Data were from 14 363 adults (≥18) who smoked cigarettes (≥monthly) and participated in at least one of the 2018, 2020 or 2022 International Tobacco Control Four Country Smoking and Vaping Surveys in Australia, Canada, England and the USA. In 2018, respondents were asked whether they would support a law that totally bans smoked tobacco if the government provides smoking cessation assistance (Cessation Assistance scenario). In 2020 and 2022, respondents were asked a slightly different question as to whether they would support a law that totally bans smoked tobacco if the government encourages people who smoke to use alternative nicotine products like vaping products and nicotine replacement products instead (substitution scenario). Responses (support vs oppose/don't know) were estimated on weighted data. RESULTS: Support was greater for the cessation assistance scenario (2018, 36.6%) than the nicotine substitution scenario (2020, 26.9%; 2022, 26.3%, both p<0.0001). In the longitudinal analysis, there was a significant scenario by country interaction effect with lower support in Canada, the USA and Australia under the substitution scenario than in the cessation scenario, but equivalent levels in England under both scenarios. The strongest correlates of support under both scenarios were planning to quit smoking within 6 months, wanting to quit smoking 'a lot' and recent use of nicotine replacement therapy. CONCLUSIONS: Opposition to banning smoked tobacco predominates among people who smoke, but less with a cessation assistance scenario than one encouraging nicotine substitution. Wanting to quit a lot was the strongest indicator of support.

Adult Female Patient with Untreated Truncus Arteriosus Type I and Torsion of Small Bowel Gastrointestinal Stromal Tumor: A Rare Case Report.

BACKGROUND Persistent truncus arteriosus is a rare congenital cyanotic heart defect characterized by a single ventricular outflow tract. Without surgical intervention, it has a poor prognosis in infancy. Here, we report an adult female patient with uncorrected truncus arteriosus type I, who presented with acute-onset abdominal pain due to torsion of a small bowel gastrointestinal stromal tumor (GIST). CASE REPORT A 41-year-old woman came to our Emergency Department with acute-onset lower abdominal pain for 2 days. Congenital heart disease, truncus arteriosus, had been diagnosed at birth, and there had been no surgical intervention. Abdominal computed tomography revealed a 10×9×12-cm mixed-density mass in the pelvic capacity. Transthoracic echocardiography revealed a 33-mm ventricular septal defect. The ascending aorta originated mainly from the right ventricle, and the pulmonary artery originated from the beginning of the aorta (type I truncus arteriosus, according to Collett and Edwards classification). After a quick and detailed preoperative workup, the patient underwent tumor resection by open surgery with general anesthesia. CONCLUSIONS This is the first case to report emergency surgery for a patient with uncorrected persistent truncus arteriosus due to torsion of a small bowel GIST. A multidisciplinary team with deep understanding of the disease entity was crucial. By considering the fixed hemodynamic and respiratory physiology, overtreatment and unrealistic goals were avoided. Eventually, the patient was discharged after being hospitalized for 2 weeks.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Liver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress ß-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model.

BACKGROUND: Cancer patients often suffer from severe stress reactions psychologically, such as anxiety and depression. Prostate cancer (PC) is one of the common cancer types, with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis. Therefore, attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment. AIM: To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model. METHODS: A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022. The patient cohort was divided into a training group (n = 84) and a validation group (n = 36) at a ratio of 7:3. The patients' anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), respectively. Logistic regression was used to analyze the risk factors affecting negative mood, and a risk prediction model was constructed. RESULTS: In the training group, 35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50, respectively. Based on the scores, we further subclassified patients into two groups: a bad mood group (n = 35) and an emotional stability group (n = 49). Multivariate logistic regression analysis showed that marital status, castration scheme, and postoperative Visual Analogue Scale (VAS) score were independent risk factors affecting a patient's bad mood (P < 0.05). In the training and validation groups, patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients (P < 0.0001). The area under the curve (AUC) of the risk prediction model for predicting bad mood in the training group was 0.743, the specificity was 70.96%, and the sensitivity was 66.03%, while in the validation group, the AUC, specificity, and sensitivity were 0.755, 66.67%, and 76.19%, respectively. The Hosmer-Lemeshow test showed a χ2 of 4.2856, a P value of 0.830, and a C-index of 0.773 (0.692-0.854). The calibration curve revealed that the predicted curve was basically consistent with the actual curve, and the calibration curve showed that the prediction model had good discrimination and accuracy. Decision curve analysis showed that the model had a high net profit. CONCLUSION: In PC patients, marital status, castration scheme, and postoperative pain (VAS) score are important factors affecting postoperative anxiety and depression. The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

Features of thromboelastogram in populations exposed to or transferring from high altitude.

Background: Thromboelastogram (TEG) is an effective indicator that monitors the dynamic changes of blood coagulation in real-time. It still remains controversial about the performance and influence of coagulation at high altitude. The present study intends to describe comprehensively the clinical features of TEG in populations exposed to or transferring from high altitude. Methods: Two groups were recruited in the present study. Group A included young males who worked at high-altitude (4888 m or 5418 m) areas for some time, while Group B included young males who had recently returned from high-altitude (4888 m or 5418 m) areas. Medical examinations were performed using portable devices. Spearman's test was used to evaluate the correlations between thromboelastogram (TEG) variables and other variables. Logistic regression analysis was used to analyze the factors affecting various abnormal TEG variables. Results: A total of 51 adult males were included in the two groups. Significantly increased reaction time (R) and decreased maximum amplitude (MA) were found in group B (P < 0.05). No significant differences were observed in the comparisons of K and angle between the two groups. Various TEG variables were identified to be correlated with different coagulation and biochemical variables. Logistic regression analysis demonstrated that abnormal R was independently associated with direct bilirubin, and abnormal K was independently associated with the platelet count in Group A (P < 0.05). However, none of the factors were independently associated with abnormal TEG variables in Group B. Conclusion: Populations exposed to or transferring from high altitudes are characterized by different TEG characteristics. Our findings give a comprehensive description of the complex interaction between TEG indexes, coagulation dynamics, and hematological parameters, which can help guide the development of appropriate medical approaches tailored to the unique needs of these populations.

Performance of the walking trail making test in older adults with white matter hyperintensities.

BACKGROUND: Several studies have reported that the walking trail making test (WTMT) completion time is significantly higher in patients with developmental coordination disorders and mild cognitive impairments. We hypothesized that WTMT performance would be altered in older adults with white matter hyperintensities (WMH). AIM: To explore the performance in the WTMT in older people with WMH. METHODS: In this single-center, observational study, 25 elderly WMH patients admitted to our hospital from June 2019 to June 2020 served as the WMH group and 20 participants matched for age, gender, and educational level who were undergoing physical examination in our hospital during the same period served as the control group. The participants completed the WTMT-A and WTMT-B to obtain their gait parameters, including WTMT-A completion time, WTMT-B completion time, speed, step length, cadence, and stance phase percent. White matter lesions were scored according to the Fazekas scale. Multiple neuropsychological assessments were carried out to assess cognitive function. The relationships between WTMT performance and cognition and motion in elderly patients with WMH were analyzed by partial Pearson correlation analysis. RESULTS: Patients with WMH performed significantly worse on the choice reaction test (CRT) (0.51 ± 0.09 s vs 0.44 ± 0.06 s, P = 0.007), verbal fluency test (VFT, 14.2 ± 2.75 vs 16.65 ± 3.54, P = 0.012), and digit symbol substitution test (16.00 ± 2.75 vs 18.40 ± 3.27, P = 0.010) than participants in the control group. The WMH group also required significantly more time to complete the WTMT-A (93.00 ± 10.76 s vs 70.55 ± 11.28 s, P < 0.001) and WTMT-B (109.72 ± 12.26 s vs 82.85 ± 7.90 s, P < 0.001). WTMT-A completion time was positively correlated with CRT time (r = 0.460, P = 0.001), while WTMT-B completion time was negatively correlated with VFT (r = -0.391, P = 0.008). On the WTMT-A, only speed was found to statistically differ between the WMH and control groups (0.803 ± 0.096 vs 0.975 ± 0.050 m/s, P < 0.001), whereas on the WTMT-B, the WMH group exhibited a significantly lower speed (0.778 ± 0.111 vs 0.970 ± 0.053 m/s, P < 0.001) and cadence (82.600 ± 4.140 vs 85.500 ± 5.020 steps/m, P = 0.039), as well as a higher stance phase percentage (65.061 ± 1.813% vs 63.513 ± 2.465%, P = 0.019) relative to controls. CONCLUSION: Older adults with WMH showed obviously poorer WTMT performance. WTMT could be a potential indicator for cognitive and motor deficits in patients with WMH.

Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. METHODS: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. RESULTS: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. CONCLUSION: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.