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 analyze the clinical and ultrasonic features of breast invasive ductal carcinoma in young women patients,and improve the accuracy of ultrasonic diagnosis of breast invasive ductal carcinoma in young patients.Methods:A retrospective study was conducted on patients with invasive ductal carcinoma who underwent surgery in the Second Hospital of Shandong University from December 2015 to June 2023,with complete clinical data,preopera-tive ultrasonography and postoperative pathology.All patients were divided into two groups:young group(≤35 year-old)and control group(>35 year-old).Univariate t-test and multivariate Logistic regression analyses were used to assess the factors.Results:There was a statistical difference between the young group and the control group in the accuracy of ultrasound diagnosis(young group 81%vs control group 94%,χ2=13.082,P=0.001).Compared with the control group,the young group had a shorter disease history,a higher proportion of multiple masses,posterior echo changes and hypo-vascular lesions(P<0.05).However,there was no statistical difference in family history of breast cancer,other cancer family history,clinical symptoms,size,lesion classification,palpation,location,aspect ratio,focus echo,shape,edge per-formance,bright ring sign,calcification characteristics,ER,PR,HER-2 and Ki67(P>0.05).Conclusion:The incidence rate of young breast IDC is low,while the misdiagnosis rate of ultrasound is relatively high.More attention should be paid when the patient has a short history,multiple masses,changes in the posterior echo and less lesion blood supply.

Aim To investigate the protective role and mechanism of ginsenoside Rg1 in myocardial inflamma-tion injury and fibrosis induced by chronic lipopolysac-charide(LPS)exposure in mice.Methods A chro-nic LPS-induced mouse model was established and ran-domly assigned to six groups:control,LPS(200 μg·kg-1),Rg1(5,10,20 mg·kg-1)and Tempol(50 mg·kg-1)groups.Cardiac function was evaluated by using echocardiography,and histopathological changes in myocardial tissue were assessed via hematoxylin-eo-sin(HE)staining,Masson's trichrome staining,and periodic acid-Schiff(PAS)staining.The expression levels of TRPC6,AIM2,NLRP3,cleaved caspase-1,IL-1β,and IL-6 were detected by Western blotting.Results Compared with the control group,the cardiac function of LPS group significantly decreased,the de-gree of myocardial injury and fibrosis was aggravated,and the expressions of TRPC6,AIM2,NLRP3,IL-1 βand IL-6 significantly increased.Compared with the LPS model group,Rg1 treatment significantly improved the cardiac function,alleviated myocardial injury and fibrosis,and inhibited the expression of TRPC6,the activation of AIM2/NLRP3 inflammasomes and the ex-pression of inflammatory factors.Conclusions Gin-senoside Rg1 can inhibit the activation of AIM2/NL-RP3 inflammasomes by down-regulating TRPC6 signa-ling,thereby reducing the chronic myocardial inflam-matory injury and fibrosis caused by chronic LPS expo-sure.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

Aim To investigate the protective role and mechanism of ginsenoside Rg1 in myocardial inflamma-tion injury and fibrosis induced by chronic lipopolysac-charide(LPS)exposure in mice.Methods A chro-nic LPS-induced mouse model was established and ran-domly assigned to six groups:control,LPS(200 μg·kg-1),Rg1(5,10,20 mg·kg-1)and Tempol(50 mg·kg-1)groups.Cardiac function was evaluated by using echocardiography,and histopathological changes in myocardial tissue were assessed via hematoxylin-eo-sin(HE)staining,Masson's trichrome staining,and periodic acid-Schiff(PAS)staining.The expression levels of TRPC6,AIM2,NLRP3,cleaved caspase-1,IL-1β,and IL-6 were detected by Western blotting.Results Compared with the control group,the cardiac function of LPS group significantly decreased,the de-gree of myocardial injury and fibrosis was aggravated,and the expressions of TRPC6,AIM2,NLRP3,IL-1 βand IL-6 significantly increased.Compared with the LPS model group,Rg1 treatment significantly improved the cardiac function,alleviated myocardial injury and fibrosis,and inhibited the expression of TRPC6,the activation of AIM2/NLRP3 inflammasomes and the ex-pression of inflammatory factors.Conclusions Gin-senoside Rg1 can inhibit the activation of AIM2/NL-RP3 inflammasomes by down-regulating TRPC6 signa-ling,thereby reducing the chronic myocardial inflam-matory injury and fibrosis caused by chronic LPS expo-sure.

OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.

This article reports a first case of combined infection with severe fever with thrombocytopenia syndrome(SFTS)and scrub typhus in Dalian City.The patient was admitted to the hospital due to recurrent fever for 7 days and loss of consciousness for 1 day.Pathogen metagenomic sequencing(mNGS),SFTSV quantitative PCR,and enzyme-linked immunosorbent assay(ELISA)IgM tests were performed,showing positive results for Orientia tsutsugamushi and SFTSV nucleic acids.Based on clinical manifestations and epidemiological history,the patient was diagnosed with combined infections.

Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.

Objective:To investigate the associations between MRI texture features and genetic mutations in clear cell renal cell carcinoma (ccRCC) and non-ccRCC (n-ccRCC).Methods:This was a cross-section study. A retrospective review was performed on 31 patients (ccRCC group 19 cases and n-ccRCC group 12 cases) diagnosed with renal cell carcinomas and underwent targeted sequencing between April 2011 and December 2021 in the Third Affiliated Hospital of Soochow University. All the patients underwent MRI examinations within two weeks before partial or radical nephrectomy. Texture features were extracted from T 1WI, T 2WI, Dixon-MRI, cortical-medulla phase (CMP), nephrographic phase (NGP), and delayed phase (DEP) images. MRI texture features with the highest value for distinguishing ccRCC from n-ccRCC were selected for subsequent analysis. The next-generation high-throughput sequencing technology was employed to analyze gene mutations in renal tumors. The correlation between mutation genes and texture features in ccRCC and n-ccRCC was analyzed using Spearman correlation coefficient. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis was performed. Results:A total of 8 MRI texture features were selected. In the ccRCC group, PTEN mutation was correlated with DEP_InverseDifferenceMoment_angle0_offset7 ( r=-0.58, P=0.009). In the non-ccRCC group, SETD2 mutation was correlated with CM_Phase_InverseDifferenceMoment_AllDirection_offset1 and Dixon_W_InverseDifferenceMoment_AllDirection_offset7 ( r=0.58, 0.63, P=0.048, 0.027), PBRM1 mutation was correlated with DE_Phase_InverseDifferenceMoment_angle0_offset7 and DE_Phase_HaraVariance ( r=0.61, -0.60, P=0.034, 0.039), and FAT1 mutation was correlated with DE_Phase_HaraVariance and NG_Phase_Inertia_angle135_offset4 ( r=0.58, 0.58, P=0.047, 0.047). The KEGG pathway annotation analysis showed that the mechanisms of the mutation genes that correlated with MRI texture features in the ccRCC group were related to the p53 signaling pathway, inositol phosphate metabolism, central carbon metabolism in cancer, EGFR tyrosine kinase inhibitor resistance, PD-L1 expression and PD-1 checkpoint pathway in cancer, and phosphatidylinositol signaling system. The mutation genes correlated with MRI texture features in the non-ccRCC group were mainly associated with lysine degradation. Conclusion:The associations are found between MRI texture features and underlying genetic mutations of ccRCC and n-ccRCC. These mutation genes have completely different enrichment pathways.