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.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective:To explore and analyze the correlation between the expression of mismatch repair(MMR)protein and programmed death ligand 1(PD-L1)in colorectal cancer(CRC)tissue and clinical pathological characteristics.Methods:The study period were from July 2021 to December 2024,200 cases of colorectal cancer patients treated in our hospital were selected as the research subjects.Collected all patient lesion tissue samples(lesion group)and adjacent tissue samples(located ≥5 cm from the tumor edge,adjacent group),and used the immunohistochemistry(IHC)method to detect the expression of Mismatch repair(MMR)(MLH1,MSH2,MSH6,and PMS2)protein and PD-L1 protein.Investigated the clinical and pathological characteristics of patients and conducted correlation analysis.Results:The positive rates of dMMR and pMMR protein expression in the lesion group were 39.00％and 70.00％,respectively,while those in the adjacent cancer group were 11.00％and 89.00％,respectively.There were significant difference compared between the lesion group and the adjacent cancer group(P＜0.05).The positive rate of PD-L1 protein expression in the lesion group were 25.00％,while that in the adjacent cancer group were 80.00％.The expression of PD-L1 protein in the lesion group were significantly lower than that in the adjacent cancer group(P＜0.05).There were significant differences in the positive rates of MMR and PD-L1 protein expression among patients with different histological differentiation,clinical stages,and lymph node metastasis(P＜0.05),while there were no significant differences in the positive rates of MMR and PD-L1 protein expression among patients of different genders,ages,and disease sites(P＞0.05).Spearman analysis showed there were correlation between the expression of MMR and PD-L1 proteins in colorectal cancer tissues and clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis(P＜0.05).Conclusion:Low expression of MMR and PD-L1 proteins are commonly observed in colorectal cancer tissues.The expression of MMR and PD-L1 proteins in colorectal cancer tissues are correlated with clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis.

Objective:To explore and analyze the correlation between the expression of mismatch repair(MMR)protein and programmed death ligand 1(PD-L1)in colorectal cancer(CRC)tissue and clinical pathological characteristics.Methods:The study period were from July 2021 to December 2024,200 cases of colorectal cancer patients treated in our hospital were selected as the research subjects.Collected all patient lesion tissue samples(lesion group)and adjacent tissue samples(located ≥5 cm from the tumor edge,adjacent group),and used the immunohistochemistry(IHC)method to detect the expression of Mismatch repair(MMR)(MLH1,MSH2,MSH6,and PMS2)protein and PD-L1 protein.Investigated the clinical and pathological characteristics of patients and conducted correlation analysis.Results:The positive rates of dMMR and pMMR protein expression in the lesion group were 39.00％and 70.00％,respectively,while those in the adjacent cancer group were 11.00％and 89.00％,respectively.There were significant difference compared between the lesion group and the adjacent cancer group(P＜0.05).The positive rate of PD-L1 protein expression in the lesion group were 25.00％,while that in the adjacent cancer group were 80.00％.The expression of PD-L1 protein in the lesion group were significantly lower than that in the adjacent cancer group(P＜0.05).There were significant differences in the positive rates of MMR and PD-L1 protein expression among patients with different histological differentiation,clinical stages,and lymph node metastasis(P＜0.05),while there were no significant differences in the positive rates of MMR and PD-L1 protein expression among patients of different genders,ages,and disease sites(P＞0.05).Spearman analysis showed there were correlation between the expression of MMR and PD-L1 proteins in colorectal cancer tissues and clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis(P＜0.05).Conclusion:Low expression of MMR and PD-L1 proteins are commonly observed in colorectal cancer tissues.The expression of MMR and PD-L1 proteins in colorectal cancer tissues are correlated with clinical pathological features such as histological differentiation,clinical staging,and lymph node metastasis.

Bilirubin,as a major endogenous substance in the human body,plays anti-inflammatory,antioxidant,and cytoprotective roles within physiological ranges,serving a critical function in maintaining metabolic balance of endogenous substances.Bilirubin metabolism is a complex physiological process regulated by multiple factors,relying on UGT1A1 enzyme catalysis and transporter protein modulation to sustain substance homeostasis.Based on the theory of traditional Chinese medicine(TCM)channel tropism and the principle of visceral syndrome differentiation,liver-channel-tropic herbs can guide medications to specific viscera and meridians,exerting targeted therapeutic effects.These herbs regulate bilirubin metabolic disorders through multi-target mechanisms,including upregulating UGT1A1 enzyme activity to promote bilirubin conjugation,modulating MRP2/OATP expression to enhance bilirubin transport,attenuating oxidative stress to reduce hepatocyte damage,inhibiting inflammatory cytokines to restore metabolic enzyme activity,activating CAR signaling pathways to regulate bile acid homeostasis.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focuses on the role of liver meridian-targeting TCM to provide a basis for its rational clinical use,and studies the effects of liver meridian-targeting TCM on bilirubin metabolism from its core mechanisms to guide its rational use and provide new ideas for the research and development of traditional Chinese medicine.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focusing on the actions of herbs that enter the liver meridian.Starting from the core mechanisms,it explores how liver meridian-entering herbs significantly impact bilirubin metabolism.Some of these herbs demonstrate dual-directional regulatory effects on bilirubin metabolism.This understanding guides their rational clinical use,provides novel ideas for TCM research and development,and promotes the modernization of TCM studies.

Hypothermia is a clinical syndrome characterized by core body temperature<35℃,caused by significant heat loss from body surface in cold environment.As a systemic cold injury,it can be lethal if treatment is delayed.Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients.In 2005,the U.S.Army Research Institute of Environmental Medicine(USARIEM)issued guidelines for the prevention and management of cold injuries,but there has been no corresponding standard in China.Therefore,Emergency Branch of Chinese Medical Rescue Association,Emergency Medical Equipment Society of China Association of Medical Equipment,Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association,and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia(2025 edition).The consensus covers the pathophysiology,etiology and epidemiology,diagnosis and severity grading,prehospital treatment,and in-hospital treatment of hypothermia,including 15 recommendations in total,aiming to provide guidance for the relevant clinical rescue work.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Bilirubin,as a major endogenous substance in the human body,plays anti-inflammatory,antioxidant,and cytoprotective roles within physiological ranges,serving a critical function in maintaining metabolic balance of endogenous substances.Bilirubin metabolism is a complex physiological process regulated by multiple factors,relying on UGT1A1 enzyme catalysis and transporter protein modulation to sustain substance homeostasis.Based on the theory of traditional Chinese medicine(TCM)channel tropism and the principle of visceral syndrome differentiation,liver-channel-tropic herbs can guide medications to specific viscera and meridians,exerting targeted therapeutic effects.These herbs regulate bilirubin metabolic disorders through multi-target mechanisms,including upregulating UGT1A1 enzyme activity to promote bilirubin conjugation,modulating MRP2/OATP expression to enhance bilirubin transport,attenuating oxidative stress to reduce hepatocyte damage,inhibiting inflammatory cytokines to restore metabolic enzyme activity,activating CAR signaling pathways to regulate bile acid homeostasis.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focuses on the role of liver meridian-targeting TCM to provide a basis for its rational clinical use,and studies the effects of liver meridian-targeting TCM on bilirubin metabolism from its core mechanisms to guide its rational use and provide new ideas for the research and development of traditional Chinese medicine.This review summarizes the mechanisms by which TCM regulates bilirubin metabolism,focusing on the actions of herbs that enter the liver meridian.Starting from the core mechanisms,it explores how liver meridian-entering herbs significantly impact bilirubin metabolism.Some of these herbs demonstrate dual-directional regulatory effects on bilirubin metabolism.This understanding guides their rational clinical use,provides novel ideas for TCM research and development,and promotes the modernization of TCM studies.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

AIM To investigate the effects of Jisuishang Formula on neurological function and ferroptosis in a rat model of cervical spondylotic myelopathy(CSM).METHODS The CSM rat models were established and randomly assigned to the model group,the Fer-1 group(2 g/kg Ferrostatin-1 via intraperitoneal injection),the low-dose(9.7 g/kg,intragastrically),medium-dose(19.4 g/kg,intragastrically)and high-dose(38.8 g/kg,intragastrically)Jisuishang Formula groups,and the sham operation group,with 6 rats in each group.Following 4 weeks of treatment administration,BBB locomotor scores and oblique plate test result were recorded to assess their neurological function in rats.Histopathological evaluation utilized HE staining for spinal cord tissue pathology,Nissl staining for Nissl body visualization,and Prussian blue staining for iron ion deposition analysis.Protein expressions of Nrf2,SLC7A11,GPX4,HO-1,TFRC and Cox2 in spinal cord tissues was detected by immunofluorescence and Western blot,while mRNA expressions were quantified using RT-qPCR.RESULTS Compared to the sham group,the CSM model group exhibited significantly reduced BBB locomotor scores and inclined plane test performance at 1,2 and 4 weeks post-operation(P＜0.05);obvious tissue cavitation,cellular edema and Prussian blue positive iron deposition in spinal cord tissues;downregulated protein and mRNA expressions of Nrf2,SLC7A11,GPX4,HO-1(P＜0.05);and upregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).Compared to the model group,the Jisuishang Formula and Fer-1 intervention groups showed significantly improved BBB scores and inclined plane test result at 1,2 and 4 weeks post-operation(P＜0.05);reduced tissue cavitation,attenuated cellular edema and decreased Prussian blue positive iron deposition in spinal cord tissues;upregulated protein and mRNA expression of Nrf2,SLC7A11,GPX4 and HO-1 in spinal cord tissues(P＜0.05);and downregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).CONCLUSION Targeting the Nrf2/SLC7A11/GPX4 signaling pathway,Jisuishang Formula potentially suppresses ferroptosis and alleviates iron accumulation in spinal cord neurons,thereby improving neurological recovery in CSM rats.