In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

Bladder tumor is a common tumor in the urinary system, posing a serious threat to patients’ health and quality of life. The standard surgical method for non-muscle-invasive bladder cancer is the transurethral resection of bladder tumor. As a new type of minimally invasive treatment, transurethral holmium laser has shown unique advantages in the treatment of bladder tumors. This work introduces the epidemiological characteristics of bladder tumors and the limitations of traditional treatment methods and elaborates on the technical principles, development history of holmium laser and its application status in the treatment of bladder tumors. By analyzing clinical research data, it compares therapeutic effects between holmium laser and other treatment methods. It also presents the key points of surgical techniques, perioperative management strategies, and measures for the prevention and treatment of complications. This research discusses the current technical challenges and future development directions in holmium laser treatment, providing references for clinical practice and research.

Background: and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD). Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert’s syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al. Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41–2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43–2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45–2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson–Neyman analyses showed cut-off concentrations of 22.3–22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not. Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.

Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

OBJECTIVE To establish the fingerprint of Gerbera delavayi and the methods for the content determination of 11 components in G. delavayi. METHODS High-performance liquid chromatography（HPLC）was adopted to establish the fingerprints of 13 batches of G. delavayi（No. S1-S13）， and the similarities were evaluated according to Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）， while the common peaks were identified. Hierarchical clustering analysis （HCA）， principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were carried out by using SPSS 25.0 software and SIMCA 14.1 software. The contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， 3，8-dihydroxy-4-methoxy-2-oxo-2H-1-benzopyran-5-carboxylic acid， caffeic acid， 3-hydroxy-4-methoxy-2- oxo-2H-1-benzopyran- 5-carboxylic acid， luteolin-7-O-β-D-glucoside， isochlorogenic acid A， apigenin-7-O-β-D-glucoside， isochlorogenic acid C and xanthotoxin were determined by HPLC. RESULTS The similarities in HPLC fingerprint of 13 batches of G. delavayi were 0.801-0.994； a total of 38 common peaks were identified and 13 common peaks were identified. The results of HCA showed that S1-S5 and S7 were clustered into one group， S6 into one category， S8 into one category， S9 and S11 into one category， S10， S12 and S13 into one category， and the results of PCA were consistent with them. The results of OPLS-DA showed that variable importance values for the projection of peak 7 （chlorogenic acid）， peak 21 （isochlorogenic acid A）， peak 26 （xanthotoxin）， peak 19 （isochlorogenic acid B）， peak 33， peak 13， peak 23 （isochlorogenic acid C）， peak 2 （new chlorogenic acid）， peak 17 （luteolin-7-O-β-D- glucoside） were greater than 1. The above 11 components had good linearity in their respective detection concentration ranges （r was greater than 0.999）. RSDs of precision， repeatability， and stability tests were not more than 2% （n＝6）. The average recovery rates were 92.54%-105.55%， and the RSDs were 0.83%-1.93% （n＝6）. The average contents of 11 components were 0.744， 5.014， 0.646， 0.431， 0.069， 0.582， 0.979， 2.754， 0.157， 1.284 and 2.943 mg/g， respectively. CONCLUSIONS The constructed HPLC fingerprint and content determination methods are simple， accurate and stable， which can provide reference for quality control of G. delavayi. Xanthotoxin， chlorogenic acid， isochlorogenic acid A， luteolin-7-O- β -D-glucoside， isochlorogenic acid C and new chlorogenic acid can be used as markers for G. delavayi.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Irradiated blood emerged as a preventive measure for transfusion-associated graft-versus-host disease (TA-GVHD), ensuring the safety of blood transfusion for patients. In recent years, with the continuous development of transfusion medicine, the utilization rate of irradiated blood has been increasing, and there has been a growing number of studies on the effects of irradiation on blood components. Meanwhile, besides preventing TA-GVHD, irradiated blood holds promising applications in addressing other clinical transfusion issues. This article reviews the clinical applications and research of irradiated blood in transfusion medicine, aiming to provide a reference for achieving safe blood transfusion.

Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.