13-Oxyingenol-dodecanoate inhibits the growth of non-small cell lung cancer cells by targeting ULK1.

Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. Euphorbia kansui yielded 13-oxyingenol-dodecanoate (13OD), an ingenane-type diterpenoid, which had a strong cytotoxic effect on NSCLC cells. The underlying mechanism and potential target, however, remained unknown. The study found that 13OD effectively inhibited the cell proliferation and colony formation of NSCLC cells (A549 and H460 cells), with less toxicity in normal human lung epithelial BEAS-2B cells. Moreover, 13OD can cause mitochondrial dysfunction, and apoptosis in NSCLC cells. Mechanistically, the transcriptomics results showed that differential genes were mainly enriched in the mTOR and AMPK signaling pathways, which are closely related to cellular autophagy, the related indicators were subsequently validated. Additionally, bafilomycin A1 (Baf A1), an autophagy inhibitor, reversed the mitochondrial damage caused by 13OD. Furthermore, the Omics and Text-based Target Enrichment and Ranking (OTTER) method predicted ULK1 as a potential target of 13OD against NSCLC cells. This hypothesis was further confirmed using molecular docking, the cellular thermal shift assay (CETSA), and Western blot analysis. Remarkably, ULK1 siRNA inhibited 13OD's toxic activity in NSCLC cells. In line with these findings, 13OD was potent and non-toxic in the tumor xenograft model. Our findings suggested a possible mechanism for 13OD's role as a tumor suppressor and laid the groundwork for identifying targets for ingenane-type diterpenoids.

The classical D1 dopamine receptor antagonist SCH23390 is a functional sigma-1 receptor allosteric modulator.

SCH23390 is a widely used D1 dopamine receptor (D1R) antagonist that also elicits some D1R-independent effects. We previously found that the benzazepine, SKF83959, an analog of SCH23390, produces positive allosteric modulation of the Sigma-1 receptor (Sig1R). SCH23390 does not bind to the orthodoxic site of Sig1R but enhances the binding of 3H (+)-pentazocine to Sig1R. In this study, we investigated whether SCH23390 functions as an allosteric modulator of Sig1R. We detected increased Sig1R dissociation from binding immunoglobulin protein (BiP) and translocation of Sig1R to the plasma membrane in response to SCH23390 in transfected HEK293T and SH-SY5Y cells, respectively. Activation of Sig1R by SCH23390 was further confirmed by inhibition of GSK3ß activity in a time- and dose-dependent manner; this effect was blocked by pretreatment with the Sig1R antagonist, BD1047, and by knockdown of Sig1R. SCH23390 also inhibited GSK3ß in wild-type mice but not in Sig1R knockout mice. Finally, we showed that SCH23390 allosterically modulated the effect of the Sig1R agonist SKF10047 on inhibition of GSK3ß. This positive allosteric effect of SCH23390 was further confirmed via promotion of neuronal protection afforded by SKF10047 in primary cortical neurons challenged with MPP+. These results provide the first evidence that SCH23390 elicits functional allosteric modulation of Sig1R. Our findings not only reveal novel pharmacological effects of SCH23390 but also indicate a potential mechanism for SCH23390-mediated D1R-independent effects. Therefore, attention should be paid to these Sig1R-mediated effects when explaining pharmacological responses to SCH23390.

Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome.

BACKGROUND: Diabetic cardiomyopathy (DCM), which is a complication of diabetes, poses a great threat to public health. Recent studies have confirmed the role of NLRP3 (NOD-like receptor protein 3) activation in DCM development through the inflammatory response. Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes. Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells. AIM: To examine the therapeutic effects of teneligliptin on DCM in diabetic mice. METHODS: Streptozotocin was administered to induce diabetes in mice, followed by treatment with 30 mg/kg teneligliptin. RESULTS: Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening, ejection fraction, and heart rate; increases in creatine kinase-MB (CK-MB), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels; and upregulated NADPH oxidase 4 were observed in diabetic mice, all of which were significantly reversed by teneligliptin. Moreover, NLRP3 inflammasome activation and increased release of interleukin-1ß in diabetic mice were inhibited by teneligliptin. Primary mouse cardiomyocytes were treated with high glucose (30 mmol/L) with or without teneligliptin (2.5 or 5 µM) for 24 h. NLRP3 inflammasome activation. Increases in CK-MB, AST, and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin, and AMP (p-adenosine 5'-monophosphate)-p-AMPK (activated protein kinase) levels were increased. Furthermore, the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C. CONCLUSION: Overall, teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

Measuring statistics-induced entanglement entropy with a Hong-Ou-Mandel interferometer.

Despite its ubiquity in quantum computation and quantum information, a universally applicable definition of quantum entanglement remains elusive. The challenge is further accentuated when entanglement is associated with other key themes, e.g., quantum interference and quantum statistics. Here, we introduce two novel motifs that characterize the interplay of entanglement and quantum statistics: an 'entanglement pointer' and a 'statistics-induced entanglement entropy'. The two provide a quantitative description of the statistics-induced entanglement: (i) they are finite only in the presence of quantum entanglement underlined by quantum statistics and (ii) their explicit form depends on the quantum statistics of the particles (e.g., fermions, bosons, and anyons). We have experimentally implemented these ideas by employing an electronic Hong-Ou-Mandel interferometer fed by two highly diluted electron beams in an integer quantum Hall platform. Performing measurements of auto-correlation and cross-correlation of current fluctuations of the scattered beams (following 'collisions'), we quantify the statistics-induced entanglement by experimentally accessing the entanglement pointer and the statistics-induced entanglement entropy. Our theoretical and experimental approaches pave the way to study entanglement in various correlated platforms, e.g., those involving anyonic Abelian and non-Abelian states.

Terahertz parametric amplification as a reporter of exciton condensate dynamics.

Condensates are a hallmark of emergence in quantum materials such as superconductors and charge density waves. Excitonic insulators are an intriguing addition to this library, exhibiting spontaneous condensation of electron-hole pairs. However, condensate observables can be obscured through parasitic coupling to the lattice. Here we employ nonlinear terahertz spectroscopy to disentangle such obscurants through measurement of the quantum dynamics. We target Ta2NiSe5, a putative room-temperature excitonic insulator in which electron-lattice coupling dominates the structural transition (Tc = 326 K), hindering identification of excitonic correlations. A pronounced increase in the terahertz reflectivity manifests following photoexcitation and exhibits a Bose-Einstein condensation-like temperature dependence well below the Tc, suggesting an approach to monitor the exciton condensate dynamics. Nonetheless, dynamic condensate-phonon coupling remains as evidenced by peaks in the enhanced reflectivity spectrum at select infrared-active phonon frequencies, indicating that parametric reflectivity enhancement arises from phonon squeezing. Our results highlight that coherent dynamics can drive parametric stimulated emission.

GMMAD: a comprehensive database of human gut microbial metabolite associations with diseases.

BACKGROUND: The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs. RESULTS: We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD . CONCLUSIONS: As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases.

Application value of multimodal MRI combined with PET metabolic parameters in temporal lobe epilepsy with dual pathology.

OBJECTIVES: To investigate the application value of multimodal MRI combined with PET metabolic parameters in detecting temporal lobe epilepsy (TLE) with dual pathology (DP) and the prediction effect of post-surgical outcomes in these patients. METHODS: We retrospectively reviewed 50 patients with TLE-DP who underwent surgery at our hospital between January 2016 and December 2021 and collected the demographics, clinical characteristics, video-electroencephalography (v-EEG), neuroimaging, and surgical data. Seizure outcome data were collected during a regular follow-up of at least 12 months and were graded using Engel scores. Fisher's exact test was used to compare the differences in DP detection rates of various diagnostic modalities. Univariate and multivariate analyses were performed to explore the prognostic factors for predicting seizure outcomes post-surgery. RESULTS: Of the 50 patients, 20 were males. The median age was 30, the median age at first seizure was 14, and the median duration was ten years. Voxel-based morphometry-PET statistical parametric mapping-PET/MRI (VBM-PSPM-PET/MRI) had the highest detection rate, followed by PET/MRI, VBM analysis, and PET-SPM. Regardless of follow-up duration, v-EEG, PET, image post-processing methods, and VBM-PSPM-PET/MRI statistically correlated with seizure outcomes using the log-rank test in the Kaplan-Meier analysis. Multivariate analysis showed that VBM-PSPM-PET/MRI was an independent predictor of TLE-DP (hazard ratio (HR) = 15.674, 95 % CI = 0.002-0.122, P < 0.00 1). CONCLUSIONS: Our study illustrates that VBM-PSPM-PET/MRI has the highest detection value in patients with TLE-DP and can provide independent prognostic information for patients who undergo surgery. This approach has the most substantial potential for the selection of candidates for patients who undergo surgical treatment and for prognostic stratification.

Anomalous universal conductance as a hallmark of non-locality in a Majorana-hosted superconducting island.

The non-local feature of topological states of matter is the key for the topological protection of quantum information and enables robust non-local manipulation in quantum information. Here we propose to manifest the non-local feature of a Majorana-hosted superconducting island by measuring the temperature dependence of Coulomb blockade peak conductance in different regimes. In the low-temperature regime, we discover a coherent double Majorana-assisted teleportation (MT) process, where any independent tunneling process always involves two coherent non-local MTs; and we also find an anomalous universal scaling behavior, i.e., a crossover from a [Formula: see text] power-law to a [Formula: see text] power-law conductance behavior when energy scale increases - in stark contrast to the usual exponential suppression due to certain local transport. In the high-temperature regime, the conductance is instead proportional to the temperature inverse, indicating a non-monotonic temperature-dependence of the conductance. Both the anomalous power law and non-monotonic temperature-dependence of the conductance can be distinguished from the conductance peak in the traditional Coulomb block, and therefore, together serve as a hallmark for the non-local feature in the Majorana-hosted superconducting island.

Direct Tie2 Agonists Stabilize Vasculature for the Treatment of Diabetic Macular Edema.

Purpose: Diabetic macular edema (DME) is the leading cause of vision loss and blindness among working-age adults. Although current intravitreal anti-vascular endothelial growth factor (VEGF) therapies improve vision for many patients with DME, approximately half do not achieve the visual acuity required to drive. We therefore sought additional approaches to resolve edema and improve vision for these patients. Methods: We explored direct agonists of Tie2, a receptor known to stabilize vasculature and prevent leakage. We identified a multivalent PEG-Fab conjugate, Tie2.1-hexamer, that oligomerizes Tie2 and drives receptor activation and characterized its activities in vitro and in vivo. Results: Tie2.1-hexamer normalized and stabilized intercellular junctions of stressed endothelial cell monolayers in vitro, suppressed vascular leak in mice under conditions where anti-VEGF alone was ineffective, and demonstrated extended ocular exposure and robust pharmacodynamic responses in non-human primates. Conclusions: Tie2.1-hexamer directly activates the Tie2 pathway, reduces vascular leak, and is persistent within the vitreal humor. Translational Relevance: Our study presents a promising potential therapeutic for the treatment of DME.

Plateau Regions for Zero-Bias Peaks within 5% of the Quantized Conductance Value 2e

Probing an isolated Majorana zero mode is predicted to reveal a tunneling conductance quantized at 2e^{2}/h at zero temperature. Experimentally, a zero-bias peak (ZBP) is expected and its height should remain robust against relevant parameter tuning, forming a quantized plateau. Here, we report the observation of large ZBPs in a thin InAs-Al hybrid nanowire device. The ZBP height can stick close to 2e^{2}/h, mostly within 5% tolerance, by sweeping gate voltages and magnetic field. We further map out the phase diagram and identify two plateau regions in the phase space. Despite the presence of disorder and quantum dots, our result constitutes a step forward toward establishing Majorana zero modes.

PEGylation of anti-MerTK Antibody Modulates Ocular Biodistribution.

Here, we explore whether PEGylation of antibodies can modulate their biodistribution to the eye, an organ once thought to be immune privileged but has recently been shown to be accessible to IV-administered large molecules, such as antibodies. We chose to PEGylate an anti-MerTK antibody, a target with known potential for ocular toxicity, to minimize biodistribution to retinal pigment epithelial cells (RPEs) in the eye by increasing the hydrodynamic volume of the antibody. We used site-specific conjugation to an engineered cysteine on anti-MerTK antibody to chemically attach 40-kDa branched or linear PEG polymers. Despite reduced binding to MerTK on cells, site-specifically PEGylated anti-MerTK retained similar potency in inhibiting MerTK-mediated macrophage efferocytosis of apoptotic cells. Importantly, we found that PEGylation of anti-MerTK significantly reduced MerTK receptor occupancy in RPE cells in both naïve mice and MC-38 tumor-bearing mice, with the branched PEG exhibiting a greater effect than linear PEG. Furthermore, similar to unconjugated anti-MerTK, PEGylated anti-MerTK antibody triggered type I IFN response and exhibited antitumor effect in syngeneic mouse tumor studies. Our results demonstrate the potential of PEGylation to control ocular biodistribution of antibodies.

Treatment outcomes and prognosis of patients with primary and acquired BRAF-mutated non-small cell lung cancer: A multicenter retrospective study.

The incidence of primary and acquired BRAF mutations is low in non-small cell lung cancer (NSCLC), with limited demographic and treatment outcome data available for this patient population. We evaluated lung cancer samples with programmed cell death ligand 1 (PD-L1) information extracted from 12 051 cases (cohort A) of lung cancer from OncoPanscan™-based sequencing of tissue (Genetron Health) and conducted retrospective multicenter data analysis using the database of Zhejiang Cancer Hospital and four other centers (cohort B, including 73 primary BRAF mutation and 14 acquired BRAF mutation cases) to compare treatment outcomes of patient groups with primary and acquired BRAF mutations. In cohort A, after propensity score analysis, 165 samples of NSCLC with BRAF mutations were screened along with 165 paired non-BRAF mutation samples. We observed no significant differences in the proportion of samples with ≥1% PD-L1 between BRAF and non-BRAF mutant groups. The median progression-free survival (mPFS) period in 13 patients with primary BRAF mutations receiving BRAF tyrosine kinase inhibitors (BRAF-TKIs) was 7.0 months. The group with primary BRAF mutations receiving immune checkpoint inhibitor (ICI) combination chemotherapy had better PFS than those administered ICI monotherapy (14.77 months vs. 5.0 months, p = 0.025) and similar results were obtained for OS (unreached vs. 20.3 months, p = 0.013). For acquired BRAF mutations, mPFS of BRAF-TKI, ICI-based, and chemotherapy-based regimens were 3.8, 1.5, and 1.9 months, respectively. Therefore, for patients with the primary BRAF V600E mutation, targeted therapy or immunochemotherapy could serve as effective treatment choices, while for those with acquired BRAF V600E, targeted drug therapy may remain the preferred solution in China.

Clinical validation of a 90-gene expression test for tumor tissue of origin diagnosis: a large-scale multicenter study of 1417 patients.

BACKGROUND: Once malignancy tumors were diagnosed, the determination of tissue origin and tumor type is critical for clinical management. Although the significant advance in imaging techniques and histopathological approaches, the diagnosis remains challenging in patients with metastatic and poorly differentiated or undifferentiated tumors. Gene expression profiling has been demonstrated the ability to classify multiple tumor types. The present study aims to assess the performance of a 90-gene expression test for tumor classification (i.e. the determination of tumor tissue of origin) in real clinical settings. METHODS: Formalin-fixed paraffin-embedded samples and associated clinicopathologic information were collected from three cancer centers between January 2016 and January 2021. A total of 1417 specimens that met quality control criteria (RNA quality, tumor cell content ≥ 60% and so on) were analyzed by the 90-gene expression test to identify the tumor tissue of origin. The performance was evaluated by comparing the test results with histopathological diagnosis. RESULTS: The 1417 samples represent 21 main tumor types classified by common tissue origins and anatomic sites. Overall, the 90-gene expression test reached an accuracy of 94.4% (1338/1417, 95% CI: 0.93 to 0.96). Among different tumor types, sensitivities were ranged from 74.2% (head&neck tumor) to 100% (adrenal carcinoma, mesothelioma, and prostate cancer). Sensitivities for the most prevalent cancers of lung, breast, colorectum, and gastroesophagus are 95.0%, 98.4%, 93.9%, and 90.6%, respectively. Moreover, specificities for all 21 tumor types are greater than 99%. CONCLUSIONS: These findings showed robust performance of the 90-gene expression test for identifying the tumor tissue of origin and support the use of molecular testing as an adjunct to tumor classification, especially to those poorly differentiated or undifferentiated tumors in clinical practice.

Universal Conductance Scaling of Andreev Reflections Using a Dissipative Probe.

The Majorana search is caught up in an extensive debate about the false-positive signals from nontopological Andreev bound states. We introduce a remedy using the dissipative probe to generate electron-boson interaction. We theoretically show that the interaction-induced renormalization leads to significantly distinct universal zero-bias conductance behaviors, i.e., distinct characteristic power law in temperature, for different types of Andreev reflections, that show a sharp contrast to that of a Majorana zero mode. Various specific cases have been studied, including the cases in which two charges involved in an Andreev reflection process maintain or lose coherence, and the cases for multiple Andreev bound states with or without a Majorana. A transparent list of conductance features in each case is provided to help distinguish the observed subgap states in experiments, which also promotes the identification of Majorana zero modes.

Suppressing Andreev Bound State Zero Bias Peaks Using a Strongly Dissipative Lead.

Hybrid semiconductor-superconductor nanowires are predicted to host Majorana zero modes that induce zero-bias peaks (ZBPs) in tunneling conductance. ZBPs alone, however, are not sufficient evidence due to the ubiquitous presence of Andreev bound states. Here, we implement a strongly resistive normal lead in InAs-Al nanowire devices and show that most of the expected Andreev bound state-induced ZBPs can be suppressed, a phenomenon known as environmental Coulomb blockade. Our result is the first experimental demonstration of this dissipative interaction effect on Andreev bound states and can serve as a possible filter to narrow down the ZBP phase diagram in future Majorana searches.

Multimodal Neuroimaging in Rett Syndrome With MECP2 Mutation.

Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by severe cognitive, social, and physical impairments resulting from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2). While there is still no cure for RTT, exploring up-to date neurofunctional diagnostic markers, discovering new potential therapeutic targets, and searching for novel drug efficacy evaluation indicators are fundamental. Multiple neuroimaging studies on brain structure and function have been carried out in RTT-linked gene mutation carriers to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed the neuroimaging literature on this disorder. MRI morphologic studies have shown global atrophy of gray matter (GM) and white matter (WM) and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral WM areas, left major WM tracts, and cingulum bilaterally, and WM microstructural/network topology changes have been further found to be correlated with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies using single-photon emission CT (SPECT) or PET have evidenced a decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unraveling metabolic alterations in patients with RTT. The results obtained from the available reports confirm that multimodal neuroimaging can provide new insights into a complex interplay between genes, neurotransmitter pathway abnormalities, disease-related behaviors, and clinical severity. However, common limitations related to the available studies include small sample sizes and hypothesis-based and region-specific approaches. We, therefore, conclude that this field is still in its early development phase and that multimodal/multisequence studies with improved post-processing technologies as well as combined PET-MRI approaches are urgently needed to further explore RTT brain alterations.

CLEC5a-directed bispecific antibody for effective cellular phagocytosis.

While antibody-dependent cellular phagocytosis mediated by activating Fcγ receptor is a key mechanism underlying many antibody drugs, their full therapeutic activities can be restricted by the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we describe a bispecific antibody approach that harnesses phagocytic receptor CLEC5A (C-type Lectin Domain Containing 5A) to drive Fcγ receptor-independent phagocytosis, potentially circumventing the negative impact of FcγRIIB. First, we established the effectiveness of such an approach by constructing bispecific antibodies that simultaneously target CLEC5A and live B cells. Furthermore, we demonstrated its in vivo application for regulatory T cell depletion and subsequent tumor regression.

[Research Progress of Magnetic Resonance Imaging-based Radiomics in Prostate Cancer].

Radiomics can extract high-throughput and quantitative image features from medical images and mine the information related to the pathophysiology of tumors,which can help clinical decision-making and improve the diagnostic and predictive performance.Radiomics has been widely used in the study of prostate cancer (PCa),demonstrating application values in the diagnosis and differential diagnosis,pathology classification,invasion assessment,efficacy prediction,and prognosis analysis of PCa.Here we reviewed the recent research progress of magnetic resonance imaging-based radiomics in PCa.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

Diffusion kurtosis imaging as an imaging biomarker for predicting prognosis in chronic kidney disease patients.

BACKGROUND: Renal fibrosis is the strongest prognostic predictor of end-stage renal disease (ESRD) in chronic kidney disease (CKD). Diffusion kurtosis imaging (DKI) is a promising method of magnetic resonance imaging successfully used to assess renal fibrosis in immunoglobulin A nephropathy. This study aimed to be the first to evaluate the long-term prognostic value of DKI in CKD patients. METHODS: Forty-two patients with CKD were prospectively enrolled, and underwent DKI on a clinical 3T MR scanner. We excluded patients with comorbidities that could affect the volume or the components of the kidney. DKI parameters, including mean Kurtosis (K), mean diffusivity and apparent diffusion coefficient (ADC) of kidney cortex were obtained by region-of-interest measurement. We followed up these patients for a median of 43 months and investigated the correlations between each DKI parameter and overall renal prognosis. RESULTS: Both K and ADC values were correlated well with the estimated glomerular filtration rate (eGFR) on recruitment and the eGFR of the last visit in follow-up (P ˂ 0.001). K and ADC values were also well associated with the eGFR slopes in CKD patients, both with the first-last time point slope (P = 0.011 and P ˂ 0.001, respectively) and with the regression slope (P = 0.010 and P ˂ 0.001, respectively). Cox proportional hazard regression indicated that lower eGFR and ADC values independently predicted eGFR loss of ˃30% and ESRD. The receiver operating characteristic analysis showed that K and ADC values were predictable for renal prognosis, and ADC displayed better capabilities for both ESRD [area under the curve (AUC) 0.936, sensitivity 92.31%, specificity 82.76%] and the composite endpoint (eGFR loss ˃30% or ESRD) (AUC 0.881, sensitivity 66.67%, specificity 96.3%). CONCLUSIONS: Renal ADC values obtained from DKI showed significant predictive value for the prognosis of CKD patients, which could be a promising noninvasive technique in follow-up.