Background/Aims: Previous studies have identified a substantial degree of agreement between the non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) populations, but the same notion may not apply to normal-weight patients with a lower cardiometabolic risk burden. This study aims to investigate the cardiometabolic risk factor (CMRF) distributions between normal-weight and overweight/obese MASLD, the agreement between historical NAFLD and MASLD, and to compare the risk of liver-related events (LREs) and all-cause mortality in normal-weight versus overweight or obese MASLD. Methods: This study included participants with steatotic liver disease (SLD) from five cohorts in China (Hong Kong), South Korea, and the United States. Participants were recruited from settings including both hospitals and communities. Individuals were classified into normal-weight and overweight/obese groups. Results: This study included 33,793 participants with SLD from five cohorts, of whom 20,893 and 20,701 patients met the diagnosis of NAFLD and MASLD, respectively. Normal-weight patients with NAFLD demonstrated a lower CMRF distribution compared to those with overweight/obese NAFLD. In the community-based cohorts, the proportions with 0 CMRF ranged from 9.0 to 26.7% among normal-weight NAFLD patients, representing the discrepancy between MASLD and NAFLD definitions. Compared with the overweight/obese MASLD, the normalweight MASLD had increased all-cause mortality (normal-weight vs. overweight/obese, 23.44 and 13.80 per 1,000 person-years; P<0.001) but not LREs (2.81 and 2.59 per 1,000 person-years; P=0.54) in the Hong Kong Clinical Data Analysis and Reporting System cohort. Conclusions Normal-weight individuals with NAFLD demonstrated a lower distribution of CMRFs, resulting in the incomplete agreement between historical NAFLD and MASLD.

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.

Caspase-8 is a cysteine-aspartate protease widely dis-tributed in cells.As a molecular"switch",caspase-8 is involved in the regulation of various modes of cell death,including apopto-sis,necroptosis and pyroptosis.During cerebral ischemia/reper-fusion,caspase-8 activation is one of the key factors inducing neuronal cell death.Currently there are both specific inhibitors of caspase-8,such as Z-IETD-FMK and Ac-IETD-CHO,as well as a variety of pan-caspase inhibitors,such as z-VAD,Q-VD-OPH,and enricosan.Both animal and cellular experiments have demonstrated that all of these inhibitors attenuate cerebral ische-mia/reperfusion injury,an effect that involves inhibition of caspase-8 activity and reduction of neuronal apoptosis.Clinical-ly,certain drugs for ischemic stroke reduce plasma caspase-8 ac-tivity,suggesting that caspase-8 may be a biomarker for the diag-nosis and prognosis of ischemic stroke.Finding and developing clinically valuable inhibitors around caspase-8 is expected to provide new ideas for new drug development in ischemic stroke.

Drynaria fortunei,commonly known as"bone setting herb",has been widely included in various traditional Chinese herb-al classics for treating bone injuries.It is used medicinally from its rhizome,which has a bitter taste and warm property.It is known to nourish the kidneys,strengthen bones,and alleviate pain from injuries.The chemical constituents mainly include flavonoids,phenylpro-panoids,triterpenoids,phenolic acids,lignans,and sterols.Modern medical research indicates that Drynaria fortunei has anti-osteoporo-sis effects,promotes fracture healing,has anti-inflammatory properties,and benefits dental health.This article reviews the historical use of Drynaria fortunei and recent research on its chemical composition and pharmacological effects,summarizing some of the mechanisms of action.The aim is to provide a reference for further research on this medicinal herb.

Drynaria fortunei,commonly known as"bone setting herb",has been widely included in various traditional Chinese herb-al classics for treating bone injuries.It is used medicinally from its rhizome,which has a bitter taste and warm property.It is known to nourish the kidneys,strengthen bones,and alleviate pain from injuries.The chemical constituents mainly include flavonoids,phenylpro-panoids,triterpenoids,phenolic acids,lignans,and sterols.Modern medical research indicates that Drynaria fortunei has anti-osteoporo-sis effects,promotes fracture healing,has anti-inflammatory properties,and benefits dental health.This article reviews the historical use of Drynaria fortunei and recent research on its chemical composition and pharmacological effects,summarizing some of the mechanisms of action.The aim is to provide a reference for further research on this medicinal herb.

Objective Based on the local anatomic relationship between right sternocleidomastoid and right internal jugular vein,the application value of modified anatomic positioning method in right internal jugular vein puncture during critical cesarean section was discussed.Methods A total of 360 critical patients who underwent elective operation in obstetrics department of our hospital were selected,all of whom received right internal jugular vein puncture. According to different puncture approaches,they were divided into the observation group (punctured by modified anatomic positioning method) and the control group (punctured by traditional middle approach method),with 180 cases in each group. The differences in the success rate of one-time puncture,the overall success rate of puncture and the failure rate of guide wire implantation were compared between the two groups. The incidence of complications such as misplacement into the artery,artery hematoma,hemopneumothorax,arrhythmia and brachial plexus injury were compared in the two groups. Results The success rate of one-time puncture and overall success rate of puncture in the observation group were significantly higher than those in the control group,and the differences were statistically significant (P<0.05). The failure rate of guide wire implantation in the observation group was lower than that in the control group,and the difference was statistically significant (P<0.05). The incidences of misplacement into the artery and artery hematoma in the observation group were significantly lower than those in the control group,and the differences were statistically significant (P<0.05). No complications such as hemopneumothorax,arrhythmia or brachial plexus injury occurred in the two groups. Conclusion Compared with the traditional middle approach method puncture,the modified anatomic positioning method puncture has the advantages of higher puncture success rate,fewer complications and higher safety.

Objective To detect the content of rheumatoid factor(RF)after RF-CIC dissociation using serum circulating immune complexes(CIC)dissociation technology and evaluate its diagnostic and clinical value in rheumatic arthritis(RA).Methods 55 RA patients diagnosed and treated in the 903rd Hospital of the People's Liberation Army from January 2024 to December 2024 were selected as the RA disease group,and 20 healthy individuals were selected as the control group.In addition,57 non RA pa-tients with symptoms resembling RA[patients with systemic lupus erythematosus(SLE),gout,ankylosing spondylitis(AS),osteo-arthritis,etc)]as the non RA disease group.Using CIC dissociation technology,RF content after RF-CIC dissociation was detect-ed in the serum of all three groups of study subjects,and C-reactive protein(CRP)and RF levels in all subjects were detected using a biochemical analyzer.Analyzed and compared the differences in the positive rate and levels of RF-CIC among three groups object of study.In addition,analyze and compare the correlation between RF-CIC and inflammatory index CRP.Results The positive rates of RF-CIC in the serum of RA disease group,non RA disease group,and control group were 87.27%(48/55),10.53%(6/57)and 0.0%(0/20),respectively,and the differences between the three groups was statistically significant(χ2=84.520,P<0.05).Further subgroup analysis showed that the RF-CIC positivity rate in the RF negative subgroup of RA disease patients[61.11%(11/18)]higher than that in the non RA disease group[1.92%(1/52)]and the control group[0%(0/20)],and the differ-ences were statistically significant(χ2=44.493,21.671,all P<0.05).The RF-CIC positivity rate was higher in RF positive pa-tients than in RF negative patients in the RA disease group(100%vs 61.11%),and the difference was statistically significant(χ2=16.487,P<0.05).The RF-CIC content in the serum of RF positive patients in the RA disease group was higher than that of RF negative patients[16.35(10.53,26.49)vs 3.57(2.53,3.89)],and the difference was statistically significant(Z=-4.243,P<0.05).Correlation analysis showed that the levels of CRP and RF in the serum of RA patients were positively correlated with the levels of RF-CIC(r=0.490,0.970,all P<0.05).Conclusion RF-CIC demonstrates high positivity even in RF-negative RA patients,and their levels correlate with CRP.RF-CIC shows potential as a serological indicator for early diagnosis and disease activity assess-ment in RA.

Objective To detect the content of rheumatoid factor(RF)after RF-CIC dissociation using serum circulating immune complexes(CIC)dissociation technology and evaluate its diagnostic and clinical value in rheumatic arthritis(RA).Methods 55 RA patients diagnosed and treated in the 903rd Hospital of the People's Liberation Army from January 2024 to December 2024 were selected as the RA disease group,and 20 healthy individuals were selected as the control group.In addition,57 non RA pa-tients with symptoms resembling RA[patients with systemic lupus erythematosus(SLE),gout,ankylosing spondylitis(AS),osteo-arthritis,etc)]as the non RA disease group.Using CIC dissociation technology,RF content after RF-CIC dissociation was detect-ed in the serum of all three groups of study subjects,and C-reactive protein(CRP)and RF levels in all subjects were detected using a biochemical analyzer.Analyzed and compared the differences in the positive rate and levels of RF-CIC among three groups object of study.In addition,analyze and compare the correlation between RF-CIC and inflammatory index CRP.Results The positive rates of RF-CIC in the serum of RA disease group,non RA disease group,and control group were 87.27%(48/55),10.53%(6/57)and 0.0%(0/20),respectively,and the differences between the three groups was statistically significant(χ2=84.520,P<0.05).Further subgroup analysis showed that the RF-CIC positivity rate in the RF negative subgroup of RA disease patients[61.11%(11/18)]higher than that in the non RA disease group[1.92%(1/52)]and the control group[0%(0/20)],and the differ-ences were statistically significant(χ2=44.493,21.671,all P<0.05).The RF-CIC positivity rate was higher in RF positive pa-tients than in RF negative patients in the RA disease group(100%vs 61.11%),and the difference was statistically significant(χ2=16.487,P<0.05).The RF-CIC content in the serum of RF positive patients in the RA disease group was higher than that of RF negative patients[16.35(10.53,26.49)vs 3.57(2.53,3.89)],and the difference was statistically significant(Z=-4.243,P<0.05).Correlation analysis showed that the levels of CRP and RF in the serum of RA patients were positively correlated with the levels of RF-CIC(r=0.490,0.970,all P<0.05).Conclusion RF-CIC demonstrates high positivity even in RF-negative RA patients,and their levels correlate with CRP.RF-CIC shows potential as a serological indicator for early diagnosis and disease activity assess-ment in RA.

Caspase-8 is a cysteine-aspartate protease widely dis-tributed in cells.As a molecular"switch",caspase-8 is involved in the regulation of various modes of cell death,including apopto-sis,necroptosis and pyroptosis.During cerebral ischemia/reper-fusion,caspase-8 activation is one of the key factors inducing neuronal cell death.Currently there are both specific inhibitors of caspase-8,such as Z-IETD-FMK and Ac-IETD-CHO,as well as a variety of pan-caspase inhibitors,such as z-VAD,Q-VD-OPH,and enricosan.Both animal and cellular experiments have demonstrated that all of these inhibitors attenuate cerebral ische-mia/reperfusion injury,an effect that involves inhibition of caspase-8 activity and reduction of neuronal apoptosis.Clinical-ly,certain drugs for ischemic stroke reduce plasma caspase-8 ac-tivity,suggesting that caspase-8 may be a biomarker for the diag-nosis and prognosis of ischemic stroke.Finding and developing clinically valuable inhibitors around caspase-8 is expected to provide new ideas for new drug development in ischemic stroke.

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans