Host-microbiota interactions contributing to the heterogeneous tumor microenvironment in colorectal cancer.

Colorectal cancer (CRC) exhibits pronounced heterogeneity and is categorized into four widely accepted consensus molecular subtypes (CMSs) with unique tumor microenvironments (TMEs). However, the intricate landscape of the microbiota and host-microbiota interactions within these TMEs remains elusive. Using RNA-sequencing data from The Cancer Genome Atlas, we analyzed the host transcriptomes and intratumoral microbiome profiles of CRC samples. Distinct host genes and microbial genera were identified among the CMSs. Immune microenvironments were evaluated using CIBERSORTx and ESTIMATE, and microbial coabundance patterns were assessed with FastSpar. Through LASSO penalized regression, we explored host-microbiota associations for each CMS. Our analysis revealed distinct host gene signatures within the CMSs, which encompassed ferroptosis-related genes and specific immune microenvironments. Moreover, we identified 293, 153, 66, and 109 intratumoral microbial genera with differential abundance, and host-microbiota associations contributed to distinct TMEs, characterized by 829, 1,270, 634, and 1,882 robust gene-microbe associations for each CMS in CMS1-CMS4, respectively. CMS1 featured inflammation-related HSF1 activation and gene interactions within the endothelin pathway and Flammeovirga. Integrin-related genes displayed positive correlations with Sutterella in CMS2, whereas CMS3 spotlighted microbial associations with biosynthetic and metabolic pathways. In CMS4, genes involved in collagen biosynthesis showed positive associations with Sutterella, contributing to disruptions in homeostasis. Notably, immune-rich subtypes exhibited pronounced ferroptosis dysregulation, potentially linked to tissue microbial colonization. This comprehensive investigation delineates the diverse landscapes of the TME within each CMS, incorporating host genes, intratumoral microbiota, and their complex interactions. These findings shed light on previously uncharted mechanisms underpinning CRC heterogeneity and suggest potential therapeutic targets.NEW & NOTEWORTHY This study determined the following: 1) providing a comprehensive landscape of consensus molecular subtype (CMS)-specific tumor microenvironments (TMEs); 2) constructing CMS-specific networks, including host genes, intratumoral microbiota, and enriched pathways, analyzing their associations to uncover unique patterns that demonstrate the intricate interplay within the TME; and 3) revealing a connection between immune-rich subtypes and ferroptosis activation, suggesting a potential regulatory role of the microbiota in ferroptosis dysregulation of the colorectal cancer TME.

Comprehensive characterization of Epimedium-Rhizoma drynariae herb pair in rat plasma, urine, and feces metabolic profiles by UHPLC-Q-Orbitrap HRMS combined with diagnostic extraction strategy and multicomponent pharmacokinetic study by UHPLC-MS/MS.

Epimedium-Rhizoma drynariae (EP-RD) was a well-known herb commonly used to treat bone diseases in traditional Chinese medicine. Nevertheless, there was incomplete pharmacokinetic behavior, metabolic conversion and chemical characterization of EP-RD in vivo. Therefore, this study aimed to establish metabolic profiles combined with multicomponent pharmacokinetics to reveal the in vivo behavior of EP-RD. Firstly, the diagnostic product ions (DPIs) and neutral losses (NLs) filtering strategy combined with UHPLC-Q-Orbitrap HRMS for the in vitro chemical composition of EP-RD and metabolic profiles of plasma, urine, and feces after oral administration of EP-RD to rats were proposed to comprehensively characterize the 47 chemical compounds and the 97 exogenous in vivo (35 prototypes and 62 metabolites), and possible biotransformation pathways of EP-RD were proposed, which included phase I reactions such as hydrolysis, hydrogenation, dehydrogenation, hydroxylation, dehydroxylation, isomerization, and demethylation and phase II reactions such as glucuronidation, acetylation, methylation, and sulfation. Moreover, a UHPLC-MS/MS quantitative approach was established for the pharmacokinetic analysis of seven active components: magnoflorine, epimedin A, epimedin B, epimedin C, icariin, baohuoside II, and icariin II. Results indicated that the established method was reliably used for the quantitative study of plasma active ingredients after oral administration of EP-RD in rats. Compared to oral EP alone, the increase in area under curves and maximum plasma drug concentration (P < 0.05). This study increased the understanding of the material basis and biotransformation profiles of EP-RD in vivo, which was of great significance in exploring the pharmacological effects of EP-RD.

Quantitative morphometric changes in vascular mild cognitive impairment patients: early diagnosis of dementia.

Vascular mild cognitive impairment (VMCI) is an early and reversible stage of dementia. Volume differences in regional gray matter may reveal the development and prognosis of VMCI. This study selected 2 of the most common types of VMCI, namely, periventricular white matter hyperintensities (PWMH, n = 14) and strategic single infarctions (SSI, n = 10), and used the voxel-based morphometry method to quantify their morphological characteristics. Meanwhile, age- and sex-matched healthy volunteers were included (n = 16). All the participants were neuropsychologically tested to characterize their cognitive function and underwent whole-brain magnetic resonance imaging scanning. Our results showed that the volumes of the bilateral temporal lobes and bilateral frontal gray matter were obviously diminished in the PWMH group. The atrophy volume difference was 4,086 voxels in the left temporal lobe, 4,154 voxels in the right temporal lobe, 1,718 voxels in the left frontal lobe, and 1,141 voxels in the right frontal lobe (P ≤ 0.001). Moreover, the characteristics of the gray matter atrophy associated with the PWMH were more similar to those associated with Alzheimer's disease than SSI, which further revealed the susceptibility for escalation from PWMH to dementia. In conclusion, PWMH patients and SSI patients have different morphological characteristics, which explain the different prognoses of VMCI.

A high level of uric acid is associated with long-term adverse cardiovascular outcomes in patients who received fractional flow reserve with coronary intermediate stenosis.

BACKGROUND AND AIMS: The role of fractional flow reserve (FFR) in coronary intermediate lesions is widely recommended by guidelines. The effect of uric acid (UA) on cardiovascular events is also well known. However, the relationship between UA and long-term cardiovascular outcomes in patients who received FFR with intermediate lesions remains unknown. METHODS AND RESULTS: We retrospectively included 428 patients who underwent both coronary angiography (CAG) and FFR. Participants were stratified into two groups based on the median UA. The primary endpoint was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including repeat revascularization, nonfatal stroke, nonfatal myocardial infarction, and all-cause death. A Cox proportional hazards model was utilized to analyze the association between UA and the prevalence of MACCEs. During a median follow-up of 5.8 years, a higher MACCEs rate occurred in the high UA group compared to the low UA group (16.8% vs. 5.1%, p log-rank<0.01). Elevated UA was independently linked to a higher incidence of MACCEs, whether UA was treated as a categorical or continuous variable (hazard ratio [HR] 2.76, 95% confidence interval [CI] 1.27-6.03 or HR 1.01, 95% CI 1.01-1.02). The restricted cubic spline (RCS) analysis illustrated that the HR for MACCEs increased with increasing UA. CONCLUSION: The present study demonstrates that UA is associated with MACCEs risk and suggests that UA is a reliable predictor of long-term cardiovascular events in coronary intermediate stenosis patients.

Triglyceride to high-density lipoprotein cholesterol ratio associated with long-term adverse clinical outcomes in patients deferred revascularization following fractional flow reserve.

BACKGROUND: Guidelines on coronary intermediate lesions strongly recommend deferred revascularization after detecting a normal fractional flow reserve (FFR). Researches about triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) on cardiovascular diseases has also been well conducted. However, the association of TG/HDL-C and long-term adverse clinical outcomes remains unknown for patients deferred revascularization following FFR. METHODS: This study retrospectively included 374 coronary artery disease (CAD) patients with non-significant coronary lesions diagnosed by coronary angiography (CAG) and FFR. The main outcome measure was the combination of major adverse cardiovascular and cerebrovascular events (MACCEs). All patients were categorized into three subgroups in terms of TG/HDL-C tertiles (T1 < 0.96, 0.96 ≤ T2 < 1.58, T3 ≥ 1.58). Three different Cox regression models were utilized to reveal the association between TG/HDL-C and prevalence of MACCEs. RESULTS: 47 MACCEs were recorded throughout a median monitoring period of 6.6 years. The Kaplan-Meier survival curves showed a higher MACCEs rate occurred in the higher TG/HDL-C group (5.6% vs. 12.9% vs. 19.4%, log-rank P < 0.01). After adjustment, patients in T3 suffered a 2.6-fold risk compared to the T1 group (T3 vs. T1: HR 2.55, 95% CI 1.05-6.21, P = 0.038; T2 vs. T1: HR 1.71, 95% CI 0.65-4.49, P = 0.075; P for trend = 0.001). The restricted cubic spline (RCS) analysis demonstrated that the HR for MACCEs rose as TG/HDL-C increased. Both the receiver operating characteristic (ROC) and time-dependent ROC proved the excellent predictive ability of TG/HDL-C. CONCLUSION: The study illustrates that TG/HDL-C correlates with the risk of MACCEs in CAD patients deferred revascularization following FFR. TG/HDL-C could serve as a dependable predictor of cardiovascular events over the long term in this population.

Association between the gut microbiota and diabetic nephropathy: a two-sample Mendelian randomization study.

Numerous studies have revealed a correlation between the risk of developing diabetic nephropathy (DN) and the gut microbiota (GM) composition. However, it remains uncertain whether the GM composition causes DN. We aimed to explore any potential causal links between the GM composition and the risk of developing DN. A meta-analysis conducted by the MiBioGen consortium of the largest genome-wide association study (GWAS) provided aggregated data on the GM. DN data were obtained from the IEU database. The inverse-variance weighting (IVW) method was employed as the primary analytical approach. The IVW analysis indicated that genus Dialister (OR = 0.51, 95% CI: 0.34-0.77, p = 0.00118) was protective against DN. In addition, class Gammaproteobacteria (OR = 0.47, 95% CI: 0.27-0.83, p = 0.0096), class Lentisphaeria (OR =0.76, 95% CI: 0.68-0.99, p = 0.04), order Victivallales (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04), and phylum Proteobacteria (OR = 0.53, 95% CI: 0.33-0.85, p = 0.00872) were negatively associated with the risk of developing DN. Genus LachnospiraceaeUCG008 (OR =1.45, 95% CI: 1.08-1.95, p = 0.01), order Bacteroidales (OR = 1.59, 95% CI: 1.02-2.49, p = 0.04), and genus Terrisporobacter (OR = 1.98, 95% CI: 1.14-3.45, p = 0.015) were positively associated with the risk of developing DN. In this study, we established a causal relationship between the genus Dialister and the risk of developing DN. Further trials are required to confirm the protective effects of probiotics on DN and to elucidate the precise protective mechanisms involving genus Dialister and DN.

[Analysis of a case of Kabuki syndrome due to a novel variant of KMT2D gene].

OBJECTIVE: To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene. METHODS: A child diagnosed with KS at the Fujian Children's Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c.6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.6285dup variant of the KMT2D gene probably underlay the KS in this child.

Metabolomic profiles in serum and urine uncover novel biomarkers in children with nephrotic syndrome.

BACKGROUND: Nephrotic syndrome is common in children and adults worldwide, and steroid-sensitive nephrotic syndrome (SSNS) accounts for 80%. Aberrant metabolism involvement in early SSNS is sparsely studied, and its pathogenesis remains unclear. Therefore, the goal of this study was to investigate the changes in initiated SSNS patients-related metabolites through serum and urine metabolomics and discover the novel potential metabolites and metabolic pathways. METHODS: Serum samples (27 SSNS and 56 controls) and urine samples (17 SSNS and 24 controls) were collected. Meanwhile, the non-targeted analyses were performed by ultra-high-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS) to determine the changes in SSNS. We applied the causal inference model, the DoWhy model, to assess the causal effects of several selected metabolites. An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to validate hits (D-mannitol, dulcitol, D-sorbitol, XMP, NADPH, NAD, bilirubin, and α-KG-like) in 41 SSNS and 43 controls. In addition, the metabolic pathways were explored. RESULTS: Compared to urine, the metabolism analysis of serum samples was more clearly discriminated at SSNS. 194 differential serum metabolites and five metabolic pathways were obtained in the SSNS group. Eight differential metabolites were identified by establishing the diagnostic model for SSNS, and four variables had a positive causal effect. After validation by targeted MS, except XMP, others have similar trends like the untargeted metabolic analysis. CONCLUSION: With untargeted metabolomics analysis and further targeted quantitative analysis, we found seven metabolites may be new biomarkers for risk prediction and early diagnosis for SSNS.

Effects of a novel ANLN E841K mutation associated with SRNS on podocytes and its mechanism.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is characterized by unrelieved proteinuria after an initial 4-8 weeks of glucocorticoid therapy. Genes in podocytes play an important role in causing SRNS. OBJECTIVE: This study aimed to report a pathogenic mutation in SRNS patients and investigate its effects on podocytes, as well as the pathogenic mechanism. METHODS: We screened out a novel mutation by using whole-exon sequencing in the SRNS cohort and verified it via Sanger sequencing. Conservative analysis and bioinformatic analysis were used to predict the pathogenicity of the mutation. In vitro, stable podocyte cell lines were constructed to detect the effect of the mutation on the function of the podocyte. Moreover, an in vivo mouse model of podocyte ANLN gene knockout (ANLNpodKO) was used to confirm clinical manifestations. Transcriptome analysis was performed to identify differential gene expression and related signaling pathways. RESULTS: ANLN E841K was screened from three unrelated families. ANLN E841K occurred in the functional domain and was predicted to be harmful. The pathological type of A-II-1 renal biopsy was minimal change disease, and the expression of ANLN was decreased. Cells in the mutation group showed disordered cytoskeleton, faster cell migration, decreased adhesion, increased endocytosis, slower proliferation, increased apoptosis, and weakened interaction with CD2 association protein. ANLNpodKO mice exhibited more obvious proteinuria, more severe mesangial proliferation, glomerular atrophy, foot process fusion, and increased tissue apoptosis levels than ANLNflox/flox mice after tail vein injection of adriamycin. Upregulated differentially expressed genes in cells of the mutation group were mainly enriched in the PI3K-AKT pathway. CONCLUSION: The novel mutation known as ANLN E841K affected the function of the ANLN protein by activating the PI3K/AKT/mTOR/apoptosis pathway, thus resulting in structural and functional changes in podocytes. Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes. Video Abstract.

Prognosis of incidental pulmonary embolism vs. symptomatic pulmonary embolism in cancer patients: a single-center retrospective cohort study in China.

BACKGROUND: The incidence of incidental pulmonary embolism (IPE) has greatly increased, but its clinical characteristics and outcomes are still controversial. This study aimed to compare the clinical characteristics and outcomes between cancer patients with IPE and patients with symptomatic pulmonary embolism (SPE). PATIENTS/METHODS: Clinical data of 180 consecutive patients with cancer complicated with pulmonary embolism admitted to Beijing Cancer Hospital from July 2011 to December 2019 were retrospectively collected and analysed. General characteristics, diagnosis time of pulmonary embolism (PE), location of PE, concurrent deep venous thrombosis, anticoagulant treatment, impact of PE on anti-tumor treatment, recurrent venous thromboembolism, rate of bleeding after anticoagulation therapy, survival and risk factors of IPE were compared with SPE. RESULTS: Of 180 patients, 88 (49%) had IPEs and 92 (51%) had SPEs. Patients with IPE and SPE did not differ in age, sex, tumor type, or tumor stage. Median diagnosis times of IPE and SPE after cancer were 108 (45, 432) days and 90 (7, 383) days, respectively. Compared to SPE, IPE tended to be central (44% versus 26%; P < 0.001), isolated (31.8% versus 0.0%; P < 0.001), and unilateral (67.1% versus 12.8%; P < 0.00). The rate of bleeding after anticoagulation therapy did not differ between IPE and SPE. Patients with IPE had a better prognosis than patients with SPE in terms of 30-, and 90-day mortality, as well as overall survival after diagnosis of PE (median: 314.5 vs. 192.0 days, log-rank P = 0.004) and cancer (median: 630.0 vs. 450.5 days, log-rank P = 0.018). SPE (compared to IPE) was an independent risk factor for poor survival after diagnosis of PE in multivariate analysis (hazard ratio [HR] = 1.564, 95% confidence interval [CI]: 1.008-2.425, p = 0.046). CONCLUSIONS: IPE accounts for nearly one half of PE cases among Chinese cancer patients. With active anticoagulation treatment, IPE is expected to achieve better survival rates than SPE.

Pd-Catalyzed Asymmetric 5-exo-trig Cyclization/Cyclopropanation/Carbonylation of 1,6-Enynes for the Construction of Chiral 3-Azabicyclo[3.1.0]hexanes.

We herein disclose a mild and efficient access to chiral 3-azabicyclo[3.1.0]hexanes via a Pd-catalyzed asymmetric 5-exo-trig cyclization/cyclopropanation/carbonylation of 1,6-enynes. Various nucleophiles, such as alcohols, phenols, amines and water, are well compatible with the reaction system. This reaction forms three C-C bonds, two rings, two adjacent quaternary carbon stereocenters as well as one C-O/C-N bond with excellent regio- and enantioselectivities. The products could be further functionalized to generate a library of 3-azabicyclo[3.1.0]hexane frameworks.

Enantioselective Synthesis of Bicyclo[3.2.1]octadienes via Palladium-Catalyzed Intramolecular Alkene-Alkyne Coupling Reaction.

Bicyclo[3.2.1]octadiene compounds and derivatives exist in a number of natural products and bioactive compounds. Nevertheless, catalytic enantioselective protocols for the synthesis of these skeletons have not been disclosed. Herein we reported a palladium-catalyzed asymmetric intramolecular alkene-alkyne coupling of alkyne-tethered cyclopentenes, affording a library of enantionenriched bicyclo[3.2.1]octadienes in excellent yields and enantioselectivities (mostly >99 % ee). Moreover, the products could undergo an unusual iodination-induced 1,2-acyl migration, forming iodinated bicyclo[3.2.1]octadienes with three vicinal stereocenters. The enone and isolated olefin motifs embedded in the products provide useful handles for downstream elaboration.

Palladium-Catalyzed Asymmetric Sequential Hydroamination of 1,3-Enynes: Enantioselective Syntheses of Chiral Imidazolidinones.

Pd-catalyzed sequential hydroamination of readily available 1,3-enynes is reported. The redox-neutral process provides an efficient route to synthesize a broad scope of imidazolidinones, thiadiazolidines, and imidazolidines. Asymmetric sequential hydroamination generates a series of synthetically valuable, enantioenriched imidazolidinones. Mechanistic studies revealed that the transformation occurred via an intermolecular enyne hydroamination pathway to give an allene intermediate. Subsequent intramolecular hydroamination of the allene intermediate proceeded under the Curtin-Hammett principle to provide enantioenriched imidazolidinone products.

Uric Acid to High-Density Lipoprotein Cholesterol Ratio is a Novel Marker to Predict Functionally Significant Coronary Artery Stenosis.

Background: Intermediate coronary stenosis (ICS) is defined as a visually estimated percentage of diameter stenosis ranging between 40% and 70% by conventional coronary angiography (CAG). Whether to perform percutaneous coronary intervention (PCI) for these lesions is a challenge in clinical practice. The fractional flow reserve (FFR) can guide treatment by determining the functional significance of ICS. Studies have shown that some clinical indicators can be used to predict FFR. However, there is little research on this in the Chinese population. Methods: We retrospectively analyzed 690 patients who underwent FFR measurements to determine the functional significance of a single ICS. Patients were divided into 2 groups: FFR ≤0.8 (n = 280) and FFR >0.8 (n = 410). We compared the clinical factors between the two groups and performed multivariate logistic regression analyses to explore the risk factors. In addition, receiver-operating characteristic (ROC) curves were constructed for FFR ≤0.8 diagnoses. Results: The mean UHR (uric acid to high-density lipoprotein cholesterol ratio) level was significantly higher in the FFR ≤0.8 group (p < 0.001). UHR corrects negatively with FFR (r = -0.44, p < 0.001). High-level UHR was an independent risk factor for the FFR ≤0.8 (OR = 7.17, 95% CI 4.17-12.34). The area under the curve (AUC) of the UHR diagnostic capacity for the FFR ≤0.8 is 0.77, with 77.3% sensitivity and 68.2% specificity. Conclusion: UHR levels were significantly increased in patients with hemodynamically significant coronary lesions. UHR is a novel predictor of functionally significant lesions in patients with a single-vessel disease of ICS.

Low Pt-Doped Crystalline/Amorphous Heterophase Pd12P3.2 Nanowires as Efficient Catalysts for Methanol Oxidation.

Pd-based catalysts are attractive anodic electrocatalysts for direct methanol fuel cells owing to their low cost and natural abundance. However, they suffer from sluggish reaction kinetic and insufficient electroactivity in methanol oxidation reaction (MOR). In this work, we developed a facile one-pot approach to fabricate low Pt-doped Pd12P3.2 nanowires with crystalline/amorphous heterophase (termed Pt-Pd12P3.2 NWs) for MOR. The unique crystalline/amorphous heterophase structures promote the catalytic activity by the plentiful active sites at the phase boundaries and/or interfaces and the synergistic effect between different phases. Moreover, the incorporation of trace Pt into Pd lattices modifies the electronic structure and improves the electron transfer ability. Therefore, the obtained Pt-Pd12P3.2 NWs display significantly enhanced electrocatalytic performance toward MOR with the mass activity of 2.35 A mgPd+Pt-1, which is 9.0, 2.9, and 2.0 times higher than those of the commercial Pd/C (0.26 A mgPd-1), Pd12P3.2 NWs (0.82 A mgPd-1), and commercial Pt/C (1.19 A mgPt-1). The high mass activity enables the Pt-Pd12P3.2 NWs to be the promising Pd-based catalysts for MOR.

Functional connectivity density alterations in children with strabismus and amblyopia based on resting-state functional magnetic resonance imaging (fMRI).

PURPOSE: To explore functional connectivity density (FCD) values of brain areas in children with strabismus and amblyopia (SA) based on blood oxygen level-dependent (BOLD) signals. METHODS: This study recruited 26 children (14 male, 12 females) with SA and 26 healthy children (14 male, 12 female) as healthy controls (HCs). Both groups matched in age, gender, educational level and socioeconomic background. While resting, all participants underwent fMRI scanning and global FCD (gFCD) and local FCD (lFCD) values were calculated. Receiver operating characteristic (ROC) curves were created to investigate whether there was a significant difference between children with SA and healthy controls. RESULTS: When compared with healthy controls, children with SA had significantly lower gFCD values in the right cerebellum, left putamen, and right superior frontal gyrus; however, the same metrics showed opposite changes in the right angular gyrus, left middle cingulate gyrus, left angular gyrus, right superior parietal gyrus, and right middle frontal gyrus. In children with SA, lFCD values were found to be remarkably decreased in regions of the middle right temporal pole, right cerebellum, left putamen, left hippocampus, right hippocampus, left thalamus, left cerebellum; values were increased in the right superior parietal gyrus as compared with healthy controls. CONCLUSION: We noted abnormal neural connectivity in some brain areas of children with SA; detailing such connectivity aberrations is useful in exploring the pathophysiology of SA and providing useful information for future clinical management.

Renoprotection with sodium-glucose cotransporter-2 inhibitors in children: Knowns and unknowns.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent novel hypoglycemic drugs for the treatment of adult diabetes that have shown considerable potential for cardioprotection and renoprotection. This new drug can inhibit SGLT2 at the proximal tubule, increase glucosuria and natriuresis, and thus decreases the serum glucose level and blood pressure. Furthermore, the tubuloglomerular feedback activated by the natriuresis can decrease glomerular hyperfiltration, acknowledged as the main foundation of renoprotection. Several studies have confirmed the protective effects of SGLT2 inhibitors on the kidneys of adult diabetic patients and those with non-diabetic nephropathy; however, limited researches are seen in paediatric patients. In this review, we have summarized the mechanisms of action of SGLT2 inhibitors, the current experiences in adults, results of exploratory studies in children, and adverse events & obstacles of paediatric use. We further explore the potential and possible future research direction of SGLT2 inhibitors in paediatric diseases.

Measuring functional connectivity in patients with strabismus using stationary functional magnetic resonance imaging: a resting-state network study.

BACKGROUND: Strabismus (STR) is a common eye disease characterized by abnormal eye movements and stereo vision. Neuroimaging studies have revealed that STR patients have impaired functional connectivity (FC) in the visual cortex and sensorimotor cortex. PURPOSE: To investigate alterations in FC and connections within and between subnetworks of the visual network (VN), sensorimotor network (SMN), and default mode network (DMN) in patients with STR. MATERIAL AND METHODS: A total of 32 patients with STR (24 men, 8 women) and 32 age- and sex-matched healthy controls (HCs) (24 men, 8 women) were recruited. Participants underwent resting-state functional magnetic resonance imaging scans. The resting-state network (RSN) was examined by independent component analysis, and differences in RSN FC between STR and HC groups were evaluated with the t test. Functional network connectivity (FNC) analysis was performed for the three RSNs. RESULTS: Compared to the HC group, the STR group showed increased FC in the VN and SMN (voxel-level P < 0.01; two-tailed Gaussian random field correction; cluster-level P < 0.05). There were no significant alterations in DMN FC between the two groups. FNC analysis of connections in the RSN revealed that one of the three connections in the VN was reduced, but no connectivity changes were observed in the SMN or DMN. FNC analysis of the connection between two RSNs showed that two had increased and one had a decreased connection value. CONCLUSION: The VN, SMN, and DMN are reorganized in patients with STR compared to HCs, providing novel insight into the neural substrates of STR.

Abnormal fractional amplitude of low-frequency fluctuations in MOG-lgG optic neuritis patients: a resting-state functional MRI study.

Optic neuritis (ON) is a general term for inflammation of any part of the optic nerve resulting from demyelination or infection. The number of patients with MOG-lgG antibody-related optic neuritis is increasing recently. Our study uses the fractional amplitude of low-frequency fluctuation (fALFF) method to compare the activity of specific brain regions in MOG-lgG ON patients and healthy controls (HCs). We selected a total of 21 MOG-lgG ON patients and 21 HCs were included in the study. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI). The independent-samples t-test was used to compare demographic data and average fALFF values between groups. The specificity and sensitivity of fALFF values for distinguishing between MOG-lgG ON patients and HCs were evaluated by receiver operating characteristic (ROC) curve analysis. Pearson's correlation analysis was used to analyze the relationship between fALFF values and clinical characteristics in MOG-lgG ON patients. Our results showed that fALFF values of the right cerebellum and left middle cingulum were lower whereas those of bilateral inferior temporal lobes, right gyrus rectus, and the left superior and right middle frontal lobes of MOG-lgG ON patients were higher than those of HCs (P < 0.05). The average fALFF value of the left superior frontal lobe in MOG-lgG ON patients was positively correlated with Hospital Anxiety and Depression Scale score (HADS) (r = 0.6004; P < 0.05) and duration of MOG-lgG ON (r = 6487; P < 0.05). Thus, patients with MOG-lgG ON have abnormal activity in the brain regions related to vision. Changes in fALFF value can reflect functional sequelae of MOG-lgG ON, including abnormal anxiety or depressive emotional changes.

Altered functional connectivity of primary visual cortex in adults with strabismus and amblyopia: a resting-state fMRI study.

Functional connectivity of the primary visual cortex was explored with resting functional magnetic resonance imaging among adults with strabismus and amblyopia and healthy controls. We used the two-sample test and receiver operating characteristic curves to investigate the differences in mean functional connectivity values between the groups with strabismus and amblyopia and healthy controls. Compared with healthy controls, functional connectivity values in the left Brodmann areas 17, including bilateral lingual/angular gyri, were reduced in groups with strabismus and amblyopia. Moreover, functional connectivity values in the right Brodmann area 17, including left cuneus, right inferior occipital gyrus, and left inferior parietal lobule, were reduced in adults with strabismus and amblyopia. Our findings indicate that functional connectivity abnormalities exist between the primary visual cortex and other regions. This may be the basis of the pathological mechanism of visual dysfunction and stereovision disorders in adults with strabismus and amblyopia.