Hyperthyroidism （HT） is frequently complicated by atrial fibrillation （AF） in clinical practice. Based on traditional Chinese medicine （TCM） zang-xiang （藏象） theory and clinical experience， both HT and AF are closely associated with dysfunction of the liver. The pathogenesis is initiated by the liver failing to govern the free flow of qi， and liver constraint and qi stagnation， with the key turning points being liver constraint transforming into fire and the internal stirring of liver wind， ultimately leading to liver blood depletion and insufficient nourishment of the heart spirit. Thus， it is proposed to treat the disease from the liver， with stage-specific therapeutic approaches according to the evolution of the disease. In the early stage， the treatment should focus on soothing the liver and relieving constraint to reduce goiter and calm the heart， while in the progressive stage， the method of clearing liver and draining fire is suggested to subdue yang and stabilize palpitations. In the acute stage， the strategy is calming the liver and nourishing yin to subdue yang and extinguish wind. In the later stage， it is suggested to soften the liver and benefit qi， so as to nourish yin and restore pulse. These methods are sequentially applied to synergistically reduce goiter and stabilize palpitations， providing a therapeutic approach for HT complicated by AF.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

ObjectiveThis study employed the scoping review method to systematically retrieve and analyze the basic information and clinical research evidence of expensive Chinese patent medicines （CPMs）， aiming to provide a basis for future related research and clinical applications. MethodsEight Chinese and English databases were systematically searched for the clinical research evidence on expensive CPMs. ResultsEleven expensive CPMs （Angong Niuhuang Wan， Jufang Zhibao Wan， Suhexiang Wan， Pien Tze Huang， Niuhuang Qingxin Wan， Qinggong Shoutao Wan， Compound Realgar Natural Indigo Tablets， Xihuang Wan， Dingkun Wan， Babao Wan， and Guilingji Capsules） were selected. A total of 365 related studies were included in this review， comprising 331 clinical studies （of which 291 were randomized controlled trials）， 30 systematic reviews and Meta-analyses， 3 expert consensus， and 1 rapid health technology assessment. Among the 11 CPMs， 2（Angong Niuhuang Wan and Jufang Zhibao Wan） had a daily price over 500 yuan. The famous and precious Chinese medicinal materials involved included Moschus （frequency of 7）， Bovisc Alculus （7）， and Borneol （5）. The dosage forms included pills， capsules， oral liquid， tablets， and lozenges. The diseases treated by these CPMs mainly included malignant tumors， cerebrovascular diseases， gynecological diseases， and hepatobiliary system diseases. The sample sizes of the clinical studies were mainly concentrated within the range of 51-100 cases， and the main control form was CPM + basic Western medicine treatment vs. basic Western medicine treatment. The 331 clinical studies reported a total of 44 adverse events occurred， of which 36 were determined to be adverse reactions. ConclusionThe scarcity of raw materials leads to the high prices of expensive CPMs. The difficulty of conducting clinical research and the critical and severe cases treated lead to a lack of clinical research evidence with large sample sizes. The uneven distribution of existing studies， incomplete information on medicine package， and non-standard clinical research designs remain to be addressed in the future.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

Plant-derived exosome-like nanovesicles refer to spherical lipid bilayer vesicles isolated from plants that contain lipids,proteins,RNAs,and various small molecules.These nanovesicles exhibit di-verse biological activities,including anti-inflammatory,anti-tumor,antioxidant,and drug delivery prop-erties.However,the functional characteristics of nanovesicles derived from rhizoma polygonati remain un-explored.In this study,exosome-like nanovesicles derived from rhizoma polygonati(referred to as RP-EVs)were successfully isolated using ultracentrifugation and density gradient centrifugation.Their physi-cochemical properties and anti-inflammatory functions were systematically characterized.Our results show that RP-EVs are predominantly negatively charged,with an average particle size of 166.5±3.3 nm,and are spherical lipid vesicles.Cellular uptake assays demonstrated that RP-EVs can be phagocytized by macrophages.qPCR and ELISA experiments revealed that RP-EVs can inhibit the elevation of interleukin 6(IL-6),interleukin 1 β(IL-1 β),and tumor necrosis factor-alpha(TNF-α)induced by lipopolysac-charide(LPS)stimulation(****P＜0.0001).Additionally,reactive oxygen species(ROS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assays confirmed that RP-EVs exhibit antioxidant proper-ties(*P＜0.05).Further investigation of the underlying mechanisms through immunofluorescence and Western blotting revealed that RP-EVs inhibit the nuclear translocation(**P＜0.01)and phosphoryla-tion(***P＜0.001)of nuclear factor kappa-B p65(NF-κB p65)via the IκBα/NF-κB signaling path-way,thereby regulating the expression of inflammatory mediators.In animal experiments,intraperitoneal injection of RP-EVs into mice for 48 hours showed predominant localization in the liver and spleen.Fi-nally,an acute inflammatory mouse model was established via intraperitoneal injection of LPS.qPCR and ELISA analyses demonstrated that RP-EVs alleviated the expression of inflammatory factors in both the serum and spleen of LPS-treated mice(*P＜0.05).In conclusion,this study isolated RP-EVs and elu-cidated their anti-inflammatory properties and potential mechanisms.These findings provide valuable in-sights into the functional exploration of nanoparticle vesicles derived from traditional Chinese medicine and suggest a novel therapeutic strategy for the treatment of inflammation-related diseases.

Mitochondria are organelles in eukaryotic cells that play a crucial role in cellular energy me-tabolism,oxidative stress,heat production,and signal transduction.Mitochondrial transplantation(MT)is currently one of the most advanced techniques for treating mitochondrial dysfunction and anti-aging re-search.This study aimed to explore the feasibility and effectiveness of xenogeneic MT by transplanting mitochondria from yak(Bos grunniens),domestic cattle(Bos taurus),and horse(Equus caballus)into mice(Mus musculus).The results demonstrated that mitochondria from yak,domestic cattle,and horse could be successfully transplanted into mice and maintained in various tissues and organs of the mice for at least 14 days,as confirmed by confocal imaging,digital PCR,and DNA sequencing.MT mice exhibi-ted positive biological effects,including increased ATP content and mitochondrial DNA copy number(P＜0.05),with the maximum effect observed on day 7,which was sustained until day 14.Reactive oxygen species(ROS)levels in MT mice significantly increased at 2 hours post-injection(P＜0.05),then grad-ually decreased towards baseline levels by day 7 and day 14(P＞0.05).These findings support the effec-tiveness of xenogeneic MT and suggest that the effects can be maintained for up to 14 days.This study provides scientific evidence for future clinical applications.

Objective To investigate the correlation between myocardial fibrosis(MF)and left ventricular ejection fraction(LVEF)and myocardial injury markers in heart failure patients via cardiac magnetic resonance(CMR).Methods Seventy-six patients with heart failure were selected,including 32 cases of heart failure with preserved ejection fraction(HFpEF)(HFpEF group),15 cases of heart failure with mid-range ejection fraction(HFmEF)(HFmEF group),and 29 patients of heart failure with reduced ejection fraction(HFrEF)(HFrEF group).Additionally,7 healthy individuals undergoing physical examinations were included(control group).CMR parameters and biological markers for the heart failure groups were collected for all subjects.The differences in native T1 value and extracellular volume fraction(ECV)between the heart failure group and the control group were compared,respectively.The differences in native T1 value,ECV,late gadolinium enhancement(LGE)score,serum creatine kinase-MB(CK-MB),cardiac troponin Ⅰ knockdown(cTnI-KD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)among heart failure subgroups were also compared,respectively.Spearman correlation analysis was used to examine the relationships between MF imaging indicators and LVEF,as well as NT-proBNP levels.Results The differences in native T1 value,ECV,LGE score,and NT-proBNP between the heart failure group and the control group,as well as between the heart failure subgroups were statistically significant(P＜0.05).The native T1 value,ECV,and LGE score in the heart failure group were positively correlated with NT-proBNP,and negatively correlated with LVEF.Conclusion The native T1 value,ECV value and LGE score are correlated with heart failure severity.CMR can detect myocardial injury early in patients with HFpEF and provide valuable information for risk stratification of MF.

Objective To observe the effect of RAW264.7 cells on calcium sparks in a insulin resistance model of C2C12 cells induced by sodium palmitate.Methods C2C12 cells and RAW264.7 cells were co-cultured to simulate the in vivo state of skeletal muscle.C2C12 cells were cultured in high-glucose medium containing 2%horse serum to induce differentiation into mature myotubes,and then divided into 5 groups:control(RAW264.7 cells),co-culture of C2C12 with RAW264.7,C2C12 alone,co-culture of C2C12 with RAW264.7 plus sodium palmitate(PA),and C2C12 alone with PA.PA of 5 mmol/L was used to induce insulin resistance in C2C12 cells for 24 hours.Revived and expanded RAW264.7 cells were evenly added to C2C12 cells and co-cultured for two days.Subsequently,cells were maintained in modified suspension culture,and both cell types were loaded with the calcium ion fluorescent probe Fluo-4 AM.Finally,Paraxanthine was used to induce intracellular calcium sparks,which was captured and recorded under a laser confocal microscope.Results No significant calcium signal change was observed in the control group.Co-cultured C2C12 cells exhibited rapid and pronounced calcium signal changes,whereas calcium signals in C2C12 cells cultured alone increased slowly throughout the observation period without a sharp decline.The peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).With PA induction,calcium signal changes in C2C12 cells were not markedly altered,while distinct calcium fluctuations were still observed in co-cultured C2C12 cells,and the peak calcium signal was reached significantly faster in co-cultured C2C12 cells than that in C2C12 cells cultured alone(P<0.001).Conclusion RAW264.7 cells enhance the dynamic responsiveness of calcium signaling in both normal and PA-stimulated C2C12 cells.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To explore the clinical characteristics and prognosis risk factors of aggressive NK-cell leukemia(ANKL).Methods:The clinical and laboratory data of 34 patients with ANKL and 15 patients with chronic lymphoproliferative disorders of NK cells(CLPD-NK)admitted to the First Affiliated Hospital of Zhengzhou University from September 2019 to December 2024 were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,and the Cox proportional hazards regression model was used to analyze prognostic factors.Results:Compared with CLPD-NK patients,ANKL patients had a younger median age of onset,a higher proportion patients with EBV-DNA≥500 copies/ml,hepatosplenomegaly and hemophagocytic syndrome.They also presented with a higher peak of fever,a shorter median survival time,lower WBC count,PLT count,ALB and Fib values,while having higher LDH,AST,TG,ferritin,CRP and PCT levels.There were statistically significant differences in the morphology and expression of HLA-DR,CD56,CD57,CD16 and CD158 on abnormall cells between ANKL patients and CLPD-NK patients.Multivariate survival analysis revealed that combined with asparaginase treatment could improve patients' survival,and CRP≥ 15 mg/L and Fib＜2.0 g/L were independent risk factors affecting the overall survival of patients with ANKL.Conclusion:The differences in clinical features and laboratory tests between patients with ANKL and CLPD-NK aid in the diagnosis of ANKL.CRP and Fib levels can be used to predict the prognosis of patients,and combined asparaginase therapy can enhance the overall survival of patients.