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］

Aberrant activation of glycolysis represents a key metabolic mechanism underlying the initiation and progression of nasal inflammation. Allergic rhinitis, chronic rhinosinusitis, and vasomotor rhinitis exhibit distinct etiologies, yet all are characterized by inflammatory responses, impaired epithelial barrier function, and neurovascular dysregulation, in which glycolytic metabolic reprogramming acts as a central hub connecting immunometabolism and inflammatory regulation.Recent evidence indicates that glycolysis-dependent activation of immune cells provides the essential energy basis for inflammatory onset. In dendritic cells, eosinophils, mast cells, and Th2 cells, the expression of key glycolytic enzymes including HK2, PKM2, and LDHA is upregulated, thereby promoting cellular activation and proinflammatory cytokine release via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.

Aberrant activation of glycolysis represents a key metabolic mechanism underlying the initiation and progression of nasal inflammation. Allergic rhinitis, chronic rhinosinusitis, and vasomotor rhinitis exhibit distinct etiologies, yet all are characterized by inflammatory responses, impaired epithelial barrier function, and neurovascular dysregulation, in which glycolytic metabolic reprogramming acts as a central hub connecting immunometabolism and inflammatory regulation.Recent evidence indicates that glycolysis-dependent activation of immune cells provides the essential energy basis for inflammatory onset. In dendritic cells, eosinophils, mast cells, and Th2 cells, the expression of key glycolytic enzymes including HK2, PKM2, and LDHA is upregulated, thereby promoting cellular activation and proinflammatory cytokine release via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.

This paper discussed the differentiation and treatment of chemotherapy-induced nausea and vomiting （CINV） in traditional Chinese medicine， based on the theory of "yin qi descends， while all yang qi ascends” from Inner Canon of Yellow Emperor （《黄帝内经》）. The core pathogenesis of CINV is attributed to chemotherapy-induced injury to the middle jiao （焦）， resulting in the separation of yin and yang and loss of their mutual communication. Acute and explosive CINV is often characterized by "all yang qi ascends"， with stomach yang constraint transforming into fire， and qi counterflow leading to vomiting， which can be treated by unblocking stomach yang， draining fire and scattering the counterflow， with Huoxiang Zhengqi Powder （藿香正气散） and medicinals of clearing function. For delayed cases， which are often due to "yin qi descends"， and the accumulation of turbid yin obstructs and constrains the deficient yang， the treatment should focus on promoting qi flow to eliminate turbidity， unblocking and boosting yang qi， and Chengqi-series Formulas （承气类方） or Xiao Banxia Decoction （小半夏汤） can be considered. Refractory and anticipated cases usually involve stomach-kidney deficiency and zang-fu （脏腑） organs disharmony， making yin and yang difficult to restore balance， for which the treatment should focus on nourishing both the stomach and kidneys and harmonize the zang-fu organs， with formulas such as Fuzi Lizhong Decoction （附子理中汤） or Xiaoyao Powder （逍遥散） modified as appropriate.

Background Previous studies have found that exposure to benzo[a]pyrene (BaP) can lead to functional impairment of the human pancreas. Pancreatic and duodenal homeobox factor 1 (PDX-1) may play a role in regulating mitochondrial function. It is hypothesized that BaP exposure may interfere with PDX-1 expression in human pancreatic ductal epithelial cells (H6C7), thereby affecting mitochondrial transcription factor A (TFAM). This process could induce mitochondrial DNA (mtDNA) damage, disrupt pancreatic development and function, and elevate the risk of diabetes onset. Objective To investigate the mechanism of BaP-induced mtDNA damage through disruption of the PDX-1/TFAM pathway in a H6C7 cell model. Methods A H6C7 cell injury model was established using different concentrations of BaP. Cell viability was determined using cell counting kit-8 (CCK-8). After 24 h of BaP exposure (5,10, and 20 μmol·L⁻¹), cell morphological and mitochondrial membrane potential (MMP) changes were observed via confocalmicroscopy, and PDX-1/TFAM protein expression levels were assessed. Bioinformatics analysis combined with dual-luciferase reporter assays was used to confirm PDX-1 directly targeting the TFAM promoter. Following PDX-1 overexpression or silencing in BaP treated cells, flow cytometry was used to evaluate viability and apoptosis, while Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) measured PDX-1/TFAM expression and mitochondrial DNA copy number (mtDNA-cn). Results The cell injury model demonstrated that, compared with the control group, BaP exposure reduced cell viability, disrupted membrane integrity, induced nuclear fragmentation, and decreased MMP. Protein expression levels of PDX-1 and TFAM were significantly downregulated in the 10 and 20 μmol·L⁻¹ groups (P<0.05). Dual-luciferase reporter assays confirmed that PDX-1 overexpression upregulated TFAM levels. Flow cytometry revealed that PDX-1 overexpression significantly reduced apoptosis rate (P<0.001), whereas PDX-1 silencing increased apoptosis rate (P<0.001). Compared with the BaP-only group, BaP+PDX-1 overexpression elevated TFAM protein and mRNA expression as well as mtDNA-cn (P<0.01), while BaP+siRNA-PDX-1 suppressed these parameters (P<0.001). Conclusion BaP exposure promotes apoptosis in human pancreatic cells. PDX-1, a key gene in pancreatic development, regulates the expression of TFAM, a core regulator of mitochondrial function. This interaction triggers changes in MMP and mtDNA-cn, activates the PDX-1/TFAM/mtDNA axis, and ultimately leads to pancreatic cell injury.

Background Previous studies have found that exposure to benzo[a]pyrene (BaP) can lead to functional impairment of the human pancreas. Pancreatic and duodenal homeobox factor 1 (PDX-1) may play a role in regulating mitochondrial function. It is hypothesized that BaP exposure may interfere with PDX-1 expression in human pancreatic ductal epithelial cells (H6C7), thereby affecting mitochondrial transcription factor A (TFAM). This process could induce mitochondrial DNA (mtDNA) damage, disrupt pancreatic development and function, and elevate the risk of diabetes onset. Objective To investigate the mechanism of BaP-induced mtDNA damage through disruption of the PDX-1/TFAM pathway in a H6C7 cell model. Methods A H6C7 cell injury model was established using different concentrations of BaP. Cell viability was determined using cell counting kit-8 (CCK-8). After 24 h of BaP exposure (5,10, and 20 μmol·L⁻¹), cell morphological and mitochondrial membrane potential (MMP) changes were observed via confocalmicroscopy, and PDX-1/TFAM protein expression levels were assessed. Bioinformatics analysis combined with dual-luciferase reporter assays was used to confirm PDX-1 directly targeting the TFAM promoter. Following PDX-1 overexpression or silencing in BaP treated cells, flow cytometry was used to evaluate viability and apoptosis, while Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) measured PDX-1/TFAM expression and mitochondrial DNA copy number (mtDNA-cn). Results The cell injury model demonstrated that, compared with the control group, BaP exposure reduced cell viability, disrupted membrane integrity, induced nuclear fragmentation, and decreased MMP. Protein expression levels of PDX-1 and TFAM were significantly downregulated in the 10 and 20 μmol·L⁻¹ groups (P<0.05). Dual-luciferase reporter assays confirmed that PDX-1 overexpression upregulated TFAM levels. Flow cytometry revealed that PDX-1 overexpression significantly reduced apoptosis rate (P<0.001), whereas PDX-1 silencing increased apoptosis rate (P<0.001). Compared with the BaP-only group, BaP+PDX-1 overexpression elevated TFAM protein and mRNA expression as well as mtDNA-cn (P<0.01), while BaP+siRNA-PDX-1 suppressed these parameters (P<0.001). Conclusion BaP exposure promotes apoptosis in human pancreatic cells. PDX-1, a key gene in pancreatic development, regulates the expression of TFAM, a core regulator of mitochondrial function. This interaction triggers changes in MMP and mtDNA-cn, activates the PDX-1/TFAM/mtDNA axis, and ultimately leads to pancreatic cell injury.

Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Objective: To evaluate the effectiveness of school-family-community comprehensive intervention aimed at reducing sugar sweetened beverage(SSB) consumption among primary and secondary school students, so as to provide scientific basis for relevant departments to formulate campus sugar reduction measures for primary and secondary school students. Methods: In October 2023, a multi stage random cluster sampling method was used to select four primary schools (grade 4) and four junior high schools (grade 7) in Nanjing City, and they were randomly divided into the intervention group ( n =1 601) and the control group ( n = 1 433 ) (primary and secondary schools). The intervention group received a one year comprehensive intervention activity with the theme of “drinking less SSBs and enjoying a healthy life” for one consecutive year. The measures included the school conducting health education courses (once a month, 15 minutes each time), environmental support (posting promotional posters, changing them once a month), class bulletin board and interest projects (once a semester); interventions for families included conducting parent lectures (once per semester 30 min each time), new media (once a month) and hand in hand activities (once per semester); community carried out square promotion and create a supportive environment (post promotional posters and replace them once a month). The control group did not receive any intervention measures except regular health education classes. Self administered questionnaires were used to collect knowledge, attitudes, and intake of SSB at the baseline and after the intervention among primary and secondary school students. Results: After the intervention, the proportion of students in the intervention group with an SSB related knowledge awareness rate of 60% or above was 91.4%, which was higher than that of the control group (81.9%) ( χ 2=60.35, P < 0.01 ). The reporting rate of the behavior of choosing to drink beverages when thirsty in the intervention group was 25.4%, which was lower than that of the control group (33.3%); the reporting rates of informing parents about the hazards of sugar sweetened beverages and paying attention to nutrition labels were 62.0% and 78.0% respectively, both of which were higher than those of the control group (52.3%, 65.9%); the reporting rate of having sugar sweetened beverages at home frequently was 43.7% in the intervention group, which was lower than that of the control group (62.3%); the reporting rate of parents restricting the consumption of sugar sweetened beverages was 84.1%, which was higher than that of the control group (78.4%) ( χ 2= 22.66, 29.05, 54.40, 104.84, 16.24, all P <0.05). The reporting rate of students in the intervention group who consumed sugar sweetened beverages more than 4 times per week was 21.5%, which was lower than that of the control group (28.6%), and the difference was statistically significant ( χ 2=20.36, P <0.01). Conclusion The comprehensive intervention of school-family-community can effectively improve primary and secondary school students knowledge and attitudes regarding SSBs and reduce their consumption of these beverages.

ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.