[Research progress in biosynthesis-related enzymes of coumarin compounds and their bioactivities].

Coumarins are natural products with benzopyran ring as the parent nucleus. Numerous coumarin derivatives exhibit a variety of pharmacological activities, including antibacterial, anti-inflammatory, antitumor, anti-coagulant, anti-osteoporotic, and insecticidal activities. Therefore, they play an important role in both medicine and agriculture. The development and utilization of coumarin derivatives have attracted increasing attention. The advancement of gene sequencing technology and the rapid progress in synthetic bio-logy have led to significant advancement in the biosynthesis of coumarin derivatives, and has received increasing attention from global researchers. This paper presents a comprehensive overview of the key biosynthesis-related enzymes of coumarin derivatives, such as cytochrome P450 enzyme(CYP450), prenyltransferase(PT), UDP-glucosyltransferase(UGT). Additionally, the pharmacological activities of these enzymes, including anti-tumor, anti-inflammatory, antioxidant, and antibacterial activities, are systematically summarized. This review aims to provide a valuable reference for the biosynthesis of coumarin derivatives and further exploration of their medicinal potential.

Cavity-Induced Optical Nonreciprocity Based on Degenerate Two-Level Atoms.

We developed and experimentally realized a scheme of optical nonreciprocity (ONR) by using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg = 4 ↔ Fe = 3, we first studied the cavity-transmission property in different coupling field configurations and verified that under the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) showed ONR. The stable ground-state Zeeman coherence for Λ-chains involved in the degenerate two-level system was found to be important in the formation of intracavity EIT. However, different from the three-level atom-cavity system, in the degenerate two-level system, the ONR effect based on intracavity EIT occurred only at a low probe intensity, because the cavity-atom coupling strength was weakened in the counter-propagating probe and coupling field configuration. Furthermore, ONR transmission with a high contrast and linewidth-narrowing was experimentally demonstrated.

Renal protective effects of helix B surface polypeptide in rats with puromycin aminonucleoside nephropathy.

BACKGROUND: Recent studies have reported that helix B surface polypeptide (HBSP), an erythropoietin derivative, exhibits strong tissue protective effects, independent of erythropoietic effects, in a renal ischemia-reperfusion (IR) injury model. Meanwhile, the transforming growth factor-ß (TGF-ß) superfamily member glial cell line-derived neurotrophic factor (GDNF) demonstrated protective effect on podocytes in vitro. Using a rat puromycin aminonucleoside nephropathy (PAN) model, this study observed the renal protective effect of HBSP and investigated its renal protective effect on podocytes and mechanism related to GDNF. METHODS: Rats nephropathy model was induced by injection of 60 mg/kg of PAN via the tail vein. Rats in the PAN + HBSP group were injected intraperitoneally with HBSP (8 nmol/kg) 4 h before the model was induced, followed by intraperitoneal injections of HBSP once every 24 h for 7 consecutive days. The 24-hour urinary protein level was measured once every other day, and blood and renal tissue samples were collected on the 7th day for the examination of renal function, complete blood count, renal pathological changes and the expression levels of GDNF. RESULTS: Compared with the control group, the PAN nephropathy rat model showed a large amount of urinary protein. The pathological manifestations were mainly extensive fusion and disappearance of foot processes, along with vacuolar degeneration of podocytes and their separation from the glomerular basement membrane. GDNF expression was upregulated. Compared with the PAN + vehicle group, the PAN + HBSP group showed decreased urinary protein (p < 0.05). Pathological examination revealed ameliorated glomerular injury and vacuolar degeneration of podocytes. The expression of GDNF in the PAN nephropathy group was increased, when compared with the control group. The greatest expression of GDNF observed in the PAN + HBSP group (p < 0.05). CONCLUSIONS: The expression of GDNF in the kidney of PAN rat model was increased. HBSP reduced urinary protein, ameliorated pathological changes in renal podocytes, increased the expression of GDNF in the PAN rat model. HBSP is likely to exert its protective effects on podocytes through upregulation of GDNF expression.

Characterization, Epitope Confirmation, and Cross-Reactivity Analysis of Parvalbumin from Lateolabrax maculatus by Multiomics Technologies.

Spotted seabass (Lateolabrax maculatus) is the second largest maricultural fish species in China and is the main trigger of food-related allergic reactions. Nevertheless, studies on the allergens of L. maculatus are limited. This study aimed to characterize pan-allergen parvalbumin from L. maculatus. Two proteins of about 11 kDa were purified and confirmed as parvalbumins by mass spectrometry. The IgG- and IgE-binding activities were evaluated through an immunoblotting assay. The molecular characteristics of ß-parvalbumin were investigated by combining proteomics, genomics, and immunoinformatics approaches. The results indicated that ß-parvalbumin consists of 109 amino acids with a molecular weight of 11.5 kDa and is the major allergen displaying strong IgE-binding capacity. In silico analysis and a dot blotting assay confirmed seven linear B cell epitopes distributed mainly on α-helixes and the calcium-binding loops. In addition, the cross-reactivity among 26 commonly consumed fish species was analyzed. The in-house generated anti-L. maculatus parvalbumin polyclonal antibody recognized 100% of the 26 fish species, demonstrating cross-reactivity and better binding capacity than the anticod parvalbumin antibody. Together, this study provides an efficient protocol to characterize allergens with multiomics methods and supports parvalbumin from L. maculatus as a candidate for fish allergen determination and allergy diagnosis.

Gene Expression Profile Identifies LncRNA AL355974.3 As a Potential Glioma Biomarker.

OBJECTIVE: Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients. METHODS: First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes. CONCLUSION: Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.

Low-temperature magnetic properties of the S = 1/2 kagomé antiferromagnet YCo3(OH)6.55Br2.45.

We report the synthesis, crystal structure, magnetization and specific heat measurements of YCo3(OH)6.55Br2.45 single crystal, in which Co2+ ions occupy a kagomé lattice. YCo3(OH)6.55Br2.45 crystallizes in trigonal structure with the formation of perfect kagomé lattice. The magnetic susceptibility reveals successive magnetic transitions at 6.5 and 7.8 K and the Curie-Weiss fitting demonstrates that YCo3(OH)6.55Br2.45 has strong antiferromagnetic coupling and pronounced magnetic frustration effect. Specific heat data suggest that low-T magnetic transitions are attributed to antiferromagnetic ordering of Co2+ ions and the magnetic entropy points to effective 1/2 spin in the system. These results indicate that an unusual magnetic ordering state with effective spin-1/2 is realized in kagomé lattice system YCo3(OH)6.55Br2.45.

Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.

Platelets promote primary hepatocellular carcinoma metastasis through TGF-ß1-mediated cancer cell autophagy.

Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.

Applying Microsoft Power Platform to Improve Primary Medical Equipment Maintenance Processes.

Post-COVID, our hospital shifted to online systems using Microsoft Power Platform to mitigate errors and delays. SharePoint and Power Apps manage equipment maintenance records and submissions, enhancing immediacy and transparency. Power Automate automates report generation and reminders, improving task completion rates. Power BI visualizes data for streamlined management. Adjustments to real-time reporting enhanced efficiency, reducing manual efforts and improving completion rates.

Applying Microsoft Power Platform to Improve Healthcare Worker Health Monitoring Processes.

Through the Microsoft Power Platform, we have developed a mobile health monitoring application, simplifying the reporting process with an individual reporting mode. Employees simply click "Very Healthy" or "Health Abnormality" and fill out the relevant information. Automated reports reduce managerial workload, enhancing satisfaction.

Extremely Large Anomalous Hall Conductivity and Unusual Axial Diamagnetism in a Quasi-1D Dirac Material La3MgBi5.

Anomalous Hall effect (AHE), one of the most important electronic transport phenomena, generally appears in ferromagnetic materials but is rare in materials without magnetic elements. Here, a study of La3MgBi5 is presented, whose band structure carries multitype Dirac fermions. Although magnetic elements are absent in La3MgBi5, the signals of AHE can be observed. In particular, the anomalous Hall conductivity is extremely large, reaching 42,356 Ω-1 cm-1 with an anomalous Hall angle of 8.8%, the largest one that has been observed in the current AHE systems. The AHE is suggested to originate from the combination of skew scattering and Berry curvature. Another unique property discovered in La3MgBi5 is the axial diamagnetism. The diamagnetism is significantly enhanced and dominates the magnetization in the axial directions, which is the result of the restricted motion of the Dirac fermion at the Fermi level. These findings not only establish La3MgBi5 as a suitable platform to study AHE and quantum transport but also indicate the great potential of 315-type Bi-based materials for exploring novel physical properties.

Use of a Penrose Drain for Decompression of a Large Periapical Lesion: A Case Report With 4.5-Year Follow-up.

Managing large cyst-like periapical lesions poses significant challenges, especially when nonsurgical treatment or retreatment options are ineffective. Despite its efficacy, decompression remains an underutilized minimally invasive alternative in modern dentistry. This case report describes the use of a Penrose drain for decompression following aspiration and irrigation to manage a large periapical lesion associated with a 56-year-old man's maxillary lateral incisor. The lesion had caused thinning and perforation of the facial and palatal cortical plates, as well as the inferior border of the nasal fossa. Cone-beam computed tomography was used to evaluate the lesion preoperatively and to assess the healing progress postoperatively. Complete 3-dimensional healing was observed after a subsequent root-end surgery performed 3.5 years post-decompression. This report suggests that decompression using a Penrose drain in combination with aspiration and irrigation could be a simple but effective modality for managing large cyst-like periapical lesions when nonsurgical endodontics are attempted and deemed ineffective.

Classification accuracy of machine learning algorithms for Chinese local cattle breeds using genomic markers.

Accurate breed classification is required for the conservation and utilization of farm animal genetic resources. Traditional classification methods mainly rely on phenotypic characterization. However, it is difficult to distinguish between the highly similar breeds due to the challenges in qualifying the phenotypic character. Machine learning algorithms show unique advantages in breed classification using genomic information. To evaluate the classification methods for Chinese cattle breeds, this study utilized genomic SNP data from 213 individuals across seven Chinese local breeds and compared the classification accuracies of three feature selection methods (FST value sorting and screening, mRMR, and Relief-F) and three machine learning algorithms (Random Forest, Support Vector Machine, and Naive Bayes). Results showed that: 1) using the FST method to screen more than 1500 SNPs, or using the mRMR algorithm to screen more than 1000 SNPs, the SVM classification algorithm can achieve more than 99.47% classification accuracy; 2) the most effective algorithm was SVM, followed by NB, while the best SNP selection method was FST and mRMR, followed by Relief-F; 3) species misclassification often occurs between breeds with high similarity. This study demonstrates that machine learning classification models combined with genomic data are effective methods for the classification of local cattle breeds, providing a technical basis for the rapid and accurate classification of cattle breeds in China.

Can We Screen for Limb Length Discrepancy on Spinal Radiographs of Patients With Adolescent Idiopathic Scoliosis?

BACKGROUND: The aim of this study was to determine whether height differences in the levels of the iliac crests and femoral heads on erect spinal radiographs can be used as indirect measurements for the screening and surveillance of limb length discrepancy (LLD) in patients with scoliosis. METHODS: Whole body posteroanterior (PA) and lateral erect radiographs of patients with adolescent idiopathic scoliosis (AIS) were retrospectively reviewed. Patients with congenital, syndromic, and neuromuscular scoliosis were excluded. A direct measurement of each limb was taken from the highest point of the femoral head to the middle of the tibial plafond; any difference between the sides was recorded as the LLD. In addition, the PACS Software tool was used to measure femoral head height difference (FHHD) and iliac crest height difference (ICHD). Pearson's correlation, linear regression, and Bland-Altman plots were used to determine the relationships between LLD and FHHD, and LLD and ICHD. RESULTS: Radiographs of 141 patients (92 women, 49 men) with an average age of 12.0±2.65 years were analyzed. A strong correlation (r=0.730, P<0.001) was found between LLD and FHHD; the correlation between LLD and ICHD was weaker (r=0.585, P<0.001). The Bland-Altman analysis showed good agreements of LLD with FHHD and ICHD. Linear regression analysis predicted an LLD of ≤10 mm based on an FHHD of ≤11.5 mm or an ICHD of ≤15.3 mm. CONCLUSIONS: FHHD and ICHD on spinal PA radiographs can be used for the screening and monitoring of LLD in patients with AIS with FHHD being the preferred indirect measurement. These measurements are readily learned and quick to perform. The FHHD and ICHD can be measured on any erect scoliosis PA radiograph. Therefore, these proxy measurements can be used to screen and monitor for LLD in patients with AIS. LEVEL OF EVIDENCE: Level III.

Fgf9 regulates bone marrow mesenchymal stem cell fate and bone-fat balance in osteoporosis by PI3K/AKT/Hippo and MEK/ERK signaling.

Bone-fat balance is crucial to maintain bone homeostasis. As common progenitor cells of osteoblasts and adipocytes, bone marrow mesenchymal stem cells (BMSCs) are delicately balanced for their differentiation commitment. However, the exact mechanisms governing BMSC cell fate are unclear. In this study, we discovered that fibroblast growth factor 9 (Fgf9), a cytokine expressed in the bone marrow niche, controlled bone-fat balance by influencing the cell fate of BMSCs. Histomorphology and cytodifferentiation analysis showed that Fgf9 loss-of-function mutation (S99N) notably inhibited bone marrow adipose tissue (BMAT) formation and alleviated ovariectomy-induced bone loss and BMAT accumulation in adult mice. Furthermore, in vitro and in vivo investigations demonstrated that Fgf9 altered the differentiation potential of BMSCs, shifting from osteogenesis to adipogenesis at the early stages of cell commitment. Transcriptomic and gene expression analyses demonstrated that FGF9 upregulated the expression of adipogenic genes while downregulating osteogenic gene expression at both mRNA and protein levels. Mechanistic studies revealed that FGF9, through FGFR1, promoted adipogenic gene expression via PI3K/AKT/Hippo pathways and inhibited osteogenic gene expression via MAPK/ERK pathway. This study underscores the crucial role of Fgf9 as a cytokine regulating the bone-fat balance in adult bone, suggesting that FGF9 is a potentially therapeutic target in the treatment of osteoporosis.

Targeting HMGCS1 restores chemotherapy sensitivity in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common hematological malignancy with overall poor prognosis. Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory (RR) AML patients. Through clinical specimens, animal models and cell-level studies, we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1) in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation, increase chemotherapy sensitivity and improve the occurrence and development of AML. Here, we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival (OS). Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity, while stable overexpression of HMGCS1 had the opposite effects. Mechanistically, we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase (MAPK) pathway activity, while overexpression of HMGCS1 could remarkably enhance the pathway. U0126, a MEK1 inhibitor, offset the effects of HMGCS1 overexpression, indicating that HMGCS1 promotes RR AML through the MAPK pathway. Further, we verified that hymeglusin, a specific inhibitor of HMGCS1, decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients. Furthermore, combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin (ADR) had synergistic toxic effects on AML cells. Our study demonstrates the important role of HMGCS1 in AML, and targeting this protein is promising for the treatment of RR AML.

Prospective cohort study evaluating efficacy and safety of efgartigimod in Chinese generalized myasthenia gravis patients.

Background: Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). Methods: This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod's therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Results: Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. Discussion: A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.

Resolution of anti-LGI1-associated autoimmune encephalitis in a patient after treatment with efgartigimod.

BACKGROUND: Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE. CASE DESCRIPTION: The patient presented with five episodes of generalized tonic-clonic seizures in the past 2 weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47 mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000 mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10 mg/kg efgartigimod was administered intravenously once a week for 2 weeks. After 2 weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3 months. CONCLUSIONS: This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan.

Tip bendable suction ureteral access sheath versus traditional sheath in retrograde intrarenal stone surgery: an international multicentre, randomized, parallel group, superiority study.

Background: Retrograde intrarenal surgery (RIRS) is the main treatments for upper urinary tract stones. The Ureteral Access Sheath (UAS) serves as a supplementary tool, facilitating direct kidney access during RIRS. High quality of evidence comparing tip bendable suction ureteral access sheath (S-UAS) with traditional UAS in RIRS for the treatment of renal and ureteral stones is lacking. The purpose of the study is to compare the efficacy and safety of S-UAS with traditional UAS in RIRS for the treatment of renal or ureteral stones ≤30 mm. Methods: An international, multicenter, and superiority randomized controlled trial included 320 intention-to-treat patients across 8 medical centers in China, the Philippines, Malaysia and Turkey from August 2023 to February 2024. The inclusion criteria were patients ≥18 years old with renal or ureteral stones ≤30 mm. RIRS was performed using either S-UAS or traditional UAS. The primary outcome was the immediately stone-free rate (SFR). Secondary outcomes included SFR 3 months after operation, operating time, hospital stay, auxiliary procedures, complications (using the Clavien-Dindo grading system), and improvement in the Quality of Life (QoL) score. Differences between proportions [risk difference (RD)]/means [mean difference (MD)] and 95% confidence intervals (CI) were presented. This study is registered at ClinicalTrials.gov: NCT05952635. Findings: The S-UAS group demonstrated a significantly higher immediately SFR (81.3% versus 49.4%; RD 31.9%; 95% CI 22.5%-41.7%; p = 0.004) compared to the traditional UAS group, as determined by the one-side superiority test. Additionally, the S-UAS group exhibited a higher SFR at 3 months post-operation (87.5% versus 70.0%; RD 17.5%; 95% CI 8.7%-26.3%; p < 0.001), lower postoperative fever rate (RD -11.9%; 95% CI -18.7% to -4.9%; p < 0.001), reduced use of stone baskets (RD -70.6%; 95% CI -77.8% to -63.5%; p < 0.001), and better QoL improvement (MD 7.25; 95% CI 2.21-12.29; p = 0.005). No statistically significant differences were observed in operation time, hospital stay, or the need for second-stage RIRS. Interpretation: In RIRS for upper urinary tract stones ≤30 mm, S-UAS exhibited superior performance compared to traditional UAS, demonstrating higher SFR, reduced postoperative fever rate, and improved QoL outcomes. S-UAS emerges as a prudent and advantageous alternative to traditional UAS for RIRS. Funding: National Natural Science Foundation of China and Guangdong Province, and Zhejiang Medicine and Health Program.