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］

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

This article reported a case of a newborn with congenital absence of the penis. The prenatal examinations were unremarkable. Physical examination of the newborn revealed abnormal external genitalia, with well-developed scrotum and fully descended testicle in normal size, but without the penis. Postnatal ultrasound showed no obvious signals of uterus and ovaries in pelvis and had normal bilateral testicles and urinary system. The diagnosis was congenital absence of the penis.

Objective To explore the effect of moxibustion on bone metabolism and the mechanism of bone protection,the effect of moxibustion,a traditional Chinese treatment in patients with rheumatoid arthritis(RA),especially the levels of two biomarkers,interleukin 35(IL-35)and β-catenin in the serum of rheumatoid arthritis patients were investigated.Methods A total of 72 RA patients were randomly assigned equally to the treatment group(36 cases)and 36 patients each of the control group(36 cases).The control group was intervened with standardized Western medicine treatment.For the treatment group,moxibustion intervened on Zusanli,Shenshu,and Ashi acupoints three times a week for 5-week treatment,with the remaining treatments being the same as the control group.The clinical symptom-related scores,routine clinical test indicators,and serum IL-35,β-catenin,BMP-2,IL-1β contents of RA patients before and after treatment were compared between the two groups.Results After treatment,VAS score,DAS28 score,morning stiffness score and BMP-2,β-catenin and IL-1β in serum in 2 groups significantly decreased(P<0.01),while IL-35 content in treatment group significantly increased(P<0.01).VAS score,DAS28 score,morning stiffness score and BMP-2,β-catenin and IL-1β in serum showed the obvious advantage of the treatment group over the control group(P<0.05),but the two groups(P>0.05)have no significant discrepancy in serum IL-35 content.For the treatment group,the improvement values of morning stiffness score and joint swelling number were positively correlated with the improvement values of BMP-2 and β-catenin in serum(P<0.01,P<0.05,r>0).The improvement of serum IL-35 was negatively correlated with the improvement of DAS28 score in the treatment group(P<0.05,r<0).Conclusion On the basis of conventional western medicine treatment,moxibustion may inhibit the levels of IL-35 and IL-1β in serum of RA patients,regulate the Wnt/β-catenin signaling pathway,regulate the levels of β-catenin and BMP-2,reduce the inflammatory response of RA,regulate bone metabolism,and achieve the purpose of bone protection.Thus,bone and joint teratogenesis or disability in RA patients was prevented and delayed.

Janus kinase inhibitors (JAKi) are a kind of small molecule targeted drugs used to treat a variety of immune-mediated inflammatory diseases by inhibiting the excessive response of a variety of cytokines. Currently, JAKi has shown good clinical efficacy, but it also has risk of major adverse cardiovascular events (MACE). The specific mechanism of JAKi-caused MACE is still unclear. This paper reviews the pharmacological molecular mechanisms and classification of JAKi and the research progress of MACE related to the JAKi (tolvaptan, baricitinib, ruxolitinib, upadacitinib, and abrocitinib) that have been approved for marketing in China. The risk factors that lead to MACE, including age, combined cardiovascular disease and inflammatory diseases, types of JAKi, dosage forms, and treatment duration are analyzed, so as to provide reference for the clinical rational use of JAKi and better prevention of MACE related to JAKi.

OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.

Objective To summarize and analyze the clinicopathological characteristics,imaging manifestations,treatment and prognosis of anaplastic lymphoma kinase(ALK)-positive histiocytosis(APH)involving the central nervous system(CNS),so as to enhance understanding of this rare disease.Methods A retrospective analysis was conducted on 5 cases of CNS-involved APH diagnosed in Huashan Hospital,Fudan University between 2019 and 2023.Clinical,imaging and pathological data were collected,and supplemented by immunohistochemical staining(IHC),fluorescence in situ hybridization(FISH)and high-throughput sequencing for auxiliary diagnosis and molecular characterization.The findings were summarized and integrated with previous literature for a comprehensive analysis.Results All five patients were male,with a mean age of 27.6 years,in which 2 cases exhibited multi-system involvement,while 3 cases exhibited single system involvement.Imaging revealed multiple intracranial lesions in multi-system cases and solitary lesions in single system cases,with well-defined boundaries and homogeneous enhancement.Histologically,tumor cells were intermingled with lymphocytes,displaying an alternating"light and dark"pattern in 1 case.Granuloma-like structures were observed in 4 cases,along with frequent nuclear grooves,indentations and convolutions.Tumor cells usually infiltrated surrounding tissues.IHC demonstrated that tumors expressed histiocytic markers(CD68/CD163)and ALK predominantly expressed in the cytoplasm.FISH confirmed ALK gene rearrangements in all patients,while high-throughput sequencing identified KIF5B-ALK fusions in 2 cases.All single system CNS cases achieved complete remission after surgical resection with or without adjuvant chemotherapy/ALK inhibitors.Among multi-system cases,one achieved partial remission,and one experienced relapse and progression.Conclusion CNS APH is prone to preoperative misdiagnosis.Its histopathological features,ALK immunohistochemical expression,and ALK gene fusions are critical for diagnosis.Patients with single system involvement demonstrate overall superior outcomes compared to multi-system cases.Total resection is effective for localized disease,while multi-system cases require systemic therapy.Multidisciplinary collaboration is crucial for precise diagnosis and treatment.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.