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］

Background: The hypotension prediction index (HPI) is an algorithm designed to predict hypotension. Some studies have reported that HPI-guided hemodynamic management strategies decrease intraoperative hypotension and complications; however, the effect of HPI on reducing perioperative complications is controversial. This meta-analysis aimed to assess the efficacy of the HPI in reducing major complications and intraoperative hypotension. Methods: We conducted this meta-analysis according to the PRISMA statement and Cochrane Handbook guidelines. A comprehensive literature review was conducted to identify studies focusing on the efficacy of HPI-guided management in reducing intraoperative hypotension and postoperative complications. The PubMed, Embase, Scopus, and Web of Science databases were searched, and the resulting data were combined to calculate the pooled mean differences or risk ratios (RRs) with 95% CIs of both randomized controlled trials (RCTs) and retrospective studies, as appropriate. Heterogeneity and potential publication bias were also assessed. Results: Nineteen articles (12 RCTs and 7 retrospective studies) with 2570 recruited patients were included in this meta-analysis. The critical evaluation of the study quality revealed a low risk of bias in the included RCTs. Among the non-randomized trials, one was rated 7, two were rated 8, and the remaining four were rated 9 on the Newcastle-Ottawa Scale, indicating high quality and a low risk of bias. HPI-guided management significantly reduced intraoperative hypotension and associated major complications (RR = 0.79, 95% CI [0.69–0.90], I2 = 0, P < 0.001). Blood loss and length of hospital stay were comparable between the groups. Conclusions HPI-guided management significantly reduced intraoperative hypotension and major complications.

Objective To investigate the capacity of municipal and county-level Centers for Disease Control (CDC) in Shandong Province for γ radionuclides in food as well as gross α and gross β in drinking water, and to provide evidence for strengthening radiological laboratories. Method Data regarding radioactive detection capacity were collected from 16 prefecture-level cities and 136 county-level CDCs. Chi-square test and Fisher's exact tests were used to compare capacity differences across regions and between cities with and without nuclear power plants. Correlation analysis was used to evaluate the spatial equity of gross α and gross β detection capacity for drinking water. Result The detection capacity of gross α and gross β in drinking water varied significantly among counties (χ²=81.026, P<0.001），no significant difference was found between coastal and inland cities (χ²=2.021，P>0.155); Cities with nuclear power plants showed better detection capacity (χ²=20.253，P<0.01). The detection capacity for γ radionuclides in food was primarily concentrated in the prefecture-level cities that host nuclear power plants. Conclusion The overall detection capacity for radioactivity in drinking water was acceptable but spatially uneven. The capacity for monitoring radioactive contamination in food was generally weak. It is necessary to strengthen capacity building at the grassroots level.

Objective: To analyze the serological phenotypes and molecular genetic characteristics of a proband with ABO forward and reverse typing discrepancy and their family members, and to investigate the molecular genetic mechanism underlying the Ael/AelB phenotype caused by the c. 575T>C variant on an ABO A1.02 background. Methods: Serological testing and adsorption-elution assays were performed for blood group identification of the proband and family members. PCR-SBT, cloning sequencing, and Nanopore third-generation sequencing were used to analyze ABO gene variants and haplotypes. Phyre2 and PyMOL were used to predict the effect of the p. Ile192Thr variant on the structure of glycosyltransferase A (GTA), and plasma GTA activity was evaluated using an in vitro transferase assay. Results: Among thirteen family members, four members showed a serological phenotype consistent with the Ael subtype and one with the AelB subtype. Cloning sequencing and third-generation sequencing confirmed that five family members carried the ABO A1.02 (c. 575T>C) variant, which co-segregated with the weak A phenotype in the family. Structural modeling suggested that p. Ile192Thr may alter the local spatial conformation and hydrogen-bond interactions of GTA. Plasma GTA activity testing showed markedly reduced GTA activity in the tested individuals. Conclusion: The ABO A1.02 (c. 575T>C) variant is associated with the Ael/AelB phenotype. The p. Ile192Thr substitution may weaken A antigen expression by altering GTA conformation and reducing enzymatic activity. This study provides additional evidence for the role of this variant in the Ael/AelB phenotype from the perspectives of familial inheritance, full-length haplotype analysis, and functional assessment, which is important for accurate ABO subtype identification and individualized transfusion strategies.

ObjectiveTo investigate the feasibility and efficacy of modified video-endoscopic inguinal lymphadenectomy （M-VEIL）， guided by the layer surgery concept， in reducing postoperative complications in patients with penile cancer. MethodsA retrospective analysis was conducted on 27 patients with penile cancer who underwent bilateral laparoscopic inguinal lymphadenectomy at the Affiliated Hospital of Qingdao University between March 2018 and March 2022. All patients had undergone prior penile surgery. M-VEIL followed a standardized four-step procedure guided by fascial planes to achieve compartment-oriented resection， with deep lymphatic trunks ligated by silk sutures and endoscopic compression suture of the skin to the muscle layer using 4-0 absorbable threads. ResultsPreoperative physical examinations and imaging findings revealed bilateral inguinal lymphadenopathy， and no distant metastases were detected in any patient. Among the 27 patients， 12 underwent traditional video-endoscopic inguinal lymphadenectomy （T-VEIL； mean age 61.08±12.75） years and 15 underwent M-VEIL （mean age 54.47±14.64） years. All 27 operations were successfully completed without conversion to open surgery. No significant differences were observed between the two groups in operative time， intraoperative blood loss， postoperative hospital stay， number of lymph nodes retrieved， or lymph node positivity rate （all P >0.05）. Drain removal time was significantly shorter in the M-VEIL group （15.93±6.89 days vs. 23.33±10.42 days； P＜0.05）. Lymphatic leakage （2 vs. 8 patients） and surgical site infection （1 vs. 6 patients） occurred less frequently in the M-VEIL group （both P ＜0.05）. No significant differences were found in lymphocele， flap necrosis， lymphedema， or lower limb edema between the two groups （all P >0.05）. During postoperative follow-up for 1-3 years， 2 patients developed pelvic lymph node metastases， while the remaining 25 showed no evidence of local or pelvic recurrence. ConclusionCompared with T-VEIL， M-VEIL appears to reduce postoperative complications and shorten drain removal time in patients undergoing inguinal lymphadenectomy for penile cancer， while providing favorable clinical outcomes. Preliminary evidence suggests that M-VEIL is a safe and feasible modified procedure.

The drug resistance in the treatment of solid tumors is closely related to abnormalities in the tumor vascular microenvironment (TVM). The TVM is dynamically composed of multiple stromal, vascular, and immune cell populations together with extracellular matrix. Its structural disorder and functional imbalance can lead to abnormal angiogenesis, perfusion disorders, limited drug delivery, and insufficient immune cell infiltration, thereby creating a microenvironment conducive to tumor progression and treatment resistance. Therefore, the coordinated regulation of TVM through vascular normalization and immune remodeling has become an important research direction for improving the treatment effect of solid tumors. Tumor necrosis factor superfamily member 14 (TNFSF14), also known as LIGHT (homologous to lymphotoxin, inducible, competes with herpes simplex virus (HSV) glycoprotein D for herpesvirus entry mediator (HVEM), expressed by T lymphocyte), is an important molecule connecting tumor vascular remodeling and immune regulation. LIGHT can bind to the lymphotoxin β receptor (LTβR) to activate the NF-κB (nuclear factor kappa B)-related signaling pathway, regulate the functions of vascular endothelial cells and stromal cells, and induce the expression of adhesion molecules and chemokines such as VCAM-1(vascular cell adhesion molecule 1), ICAM-1(intercellular adhesion molecule 1), CCL19 (C-C motif chemokine ligand 19), CCL21 (C-C motif chemokine ligand 21), and CXCL13 (C-X-C motif chemokine ligand 13), promoting the formation of high endothelial venules (HEVs). HEVs can improve the vascular access of immune cells into tumor tissues and further promote the formation of tertiary lymphoid structures (TLS), providing a structural basis for the recruitment of effector T cells and sustained anti-tumor immune responses. At the same time, LIGHT interacts with HVEM to provide costimulatory signals to T cells, enhancing their activation, proliferation, and cytotoxic function. Thus, LIGHT can link tumor vascular normalization, immune cell recruitment, and T cell activation through the dual actions mediated by LTβR and HVEM, forming a coordinated regulation model of “vascular remodeling-immune infiltration-immune activation”, providing new molecular targets for the treatment of solid tumors. Despite LIGHT’s good anti-tumor potential, its therapeutic application is still limited by factors such as insufficient stability in vivo, short half-life, and potential off-target effects due to systemic exposure. In recent years, researchers have developed various strategies for the precise delivery of LIGHT, including fusion proteins, bacterial vectors, viral vectors, nanoparticles, chimeric antigen receptor T cells (CAR-T), and mesenchymal stem cells (MSCs), to enhance the enrichment, expression, or sustained release of LIGHT in tumor sites through different approaches, thereby improving its therapeutic efficacy and safety. This article systematically reviews the structural characteristics, biological functions, and molecular mechanisms mediating TVM remodeling by LIGHT, with a focus on the signal transduction mediated by LTβR and HVEM and their roles in tumor immune regulation. Subsequently, it systematically outlines the molecular mechanisms by which LIGHT regulates the tumor vascular microenvironment and its intrinsic connection with immune cell recruitment and activation, from the perspectives of TVM abnormalities, vascular normalization, HEV formation, and TLS induction. Furthermore, it categorizes and summarizes precise delivery strategies such as LIGHT fusion proteins, bacterial vectors, viral vectors, nanoparticles, CAR-T cells, and MSCs according to delivery vectors and modes of action, and compares their functional characteristics, antitumor effects, and potential advantages and limitations. On this basis, the article further discusses the key issues that LIGHT therapeutic strategies still face in terms of targeting, controllability,in vivo stability, safety, and clinical translation, and anticipates the potential value of its combination with immune checkpoint inhibitors, anti-angiogenic therapy, and other tumor treatment methods. This article aims to deepen the understanding of the antitumor mechanism of LIGHT from the perspective of synergistic regulation of tumor vascular microenvironment remodeling and immune activation, providing theoretical basis and new research ideas for the design of solid tumor treatment strategies based on precise regulation of TVM and the clinical translation of LIGHT-related treatment systems.

Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.