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.

Objective:To analyze the prevalence trends and epidemiological characteristics of cardiometabolic multimorbidity(CMM) in Beijing from 2005 to 2022.Methods:A series of representative cross-sectional surveys were conducted in Beijing between 2005 and 2022 using a stratified multistage cluster random sampling method. A total of 110 496 permanent residents aged 18-79 years participated in face-to-face interviews, physical examinations, and laboratory testing. Complex sampling logistic regression models were employed to identify factors associated with CMM, and Joinpoint regression was used to assess temporal trends in prevalence. Results:The prevalence of CMM was 22.3% in 2005 and 24.3% in 2022, with an average annual percent change of 0.1%(95% CI -1.3%-1.3%, P>0.05). In rural areas, the prevalence increased by 1.3% per year(95% CI 0.2%-2.6%, P<0.05), while among obese individuals, it decreased by 1.0% annually( P<0.05). The most common CMM patterns were hypertension combined with dyslipidemia(13.2%), hypertension combined with diabetes(7.0%), and diabetes combined with dyslipidemia(5.8%). The prevalence of hypertension and dyslipidemia comorbidity showed a long-term decline among females, those aged 60-79 and obese individuals( P<0.05). In contrast, the prevalence of hypertension and diabetes comorbidity increased over time in rural residents and individuals with normal body weight( P<0.05). Furthermore, diabetes and dyslipidemia comorbidity rates increased significantly among males, adults aged 18-59 years, those with a college education or above, rural residents and individuals with normal body weight( P<0.05). Multivariable logistic regression indicated that male, older age, overweight, obese, and lower education level were independently associated with a higher risk of CMM( P<0.05). Conclusion:From 2005 to 2022, the prevalence of CMM remained high among adults in Beijing. While prevalence decreased among obese individuals, it increased significantly in rural areas. Hypertension combined with dyslipidemia was the most common multimorbidity pattern throughout the study period.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Objective:To evaluate the effect of toric collamer lens (TICL) rotation on myopia combined with astigmatism correction after V4c TICL implantation using standardized vector analysis.Methods:An observational case series study was performed.A total of 152 patients (268 eyes) who underwent V4c TICL implantation for the correction of myopia and myopic astigmatism were enrolled at Henan Eye Hospital from January to December 2021.The preoperative spherical diopter, cylindrical diopter, and spherical equivalent (SE) were -15.00 to -3.25 D, -5.00 to -0.50 D, -16.50 to -3.88 D, respectively.Postoperative TICL vault and axis were measured by anterior segment optical coherence tomography, and postoperative TICL rotation was calculated.Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), spherical diopter, cylindrical diopter, SE, and target astigmatism vector were recorded before and 1 month after surgery.The effectiveness index, safety index, surgically induced astigmatism vector (SIA), margin of error (ME), absolute value of the difference vector |DV|, correction index (CI), and achievement index (IS) were calculated based on the subjective refraction results 1 month after surgery and the cylindrical axis of the V4c TICL.Vector analysis parameters was compared among patients with different preoperative astigmatism, intraoperative TICL fixation, postoperative TICL rotation, and postoperative vault.The correlation between postoperative TICL rotation and TICL fixed angle deviation, postoperative vault, visual acuity and refraction, and vector analysis parameters were evaluated.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]).Written informed consent was obtained from each subject.Results:At 1 month postoperatively, the mean safety and efficacy indices were 1.27 and 1.29, respectively.There was no statistically significant difference between the predicted SE of (-0.11±0.13)D and the postoperative SE of (-0.07±0.52)D ( t=-0.994, P=0.321).UCVA, BCVA and cylinder diopter in the operative eyes were all improved after surgery compared to before surgery and the differences were statistically significant ( t=17.854, 5.446, -25.634; all P<0.001).The rotation of V4c TICL was 0° to 25°, with a mean of (5.41±4.35)°, which was positively correlated with the V4c TICL fixed angle deviation ( rs=0.461, P<0.001), negatively correlated with postoperative cylindrical diopter and positively correlated with postoperative UCVA, |DV| and SIA ( r=-0.360, 0.191, 0.205, 0.142; all P<0.05).Vector analysis between groups showed that vault, SIA and |DV| were higher and CI and IS were lower in low astigmatism group than in high astigmatism group ( Z=-3.017, -13.569, -2.793, -2.761, -4.779; all P<0.05).V4c TICL rotation and |DV| were lower in low fixation angle difference group than in high fixation angle difference group ( Z=-7.865, -2.080; both P<0.05).Preoperative cylindrical diopter, intraoperative V4c TICL fixed angle deviation, SIA and |DV| were lower in low rotation group than in high rotation group ( Z=-2.104, -4.578, -2.456, -2.090; all P<0.05).There were no statistically significant differences in the TICL rotation or in each vector between patients with different vault after the surgery (all P>0.05). Conclusions:V4c TICL implantation can achieve good results for the correction of myopia and myopic astigmatism.There is a slight difference between the fixation axis and the target axis of V4c TICL, which affects the rotation of V4c TICL and |DV|.Postoperative V4c TICL rotation is related to TICL fixed angle deviation, postoperative UCVA, SIA, |DV| and postoperative cylindrical diopter.Postoperative vault has no significant effect on TICL rotation and differences in each vector.

Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.

Hypercholesterolemia is pathologically characterized by abnormal accumulation of low-density lipoprotein cholesterol,which is closely associated with metabolic dysfunction-associated fatty liver disease and increased cardiovascular risks.Hepatocytes maintain cholesterol homeostasis through LDL receptor-mediated uptake and esterification storage mechanisms.However,chronic cholesterol overload induces mitochondrial dysfunction,reactive oxygen species accumulation,and endoplasmic reticulum stress,leading to hepatocyte injury.Moreover,systemic hypercholesterolemia disrupts gut microbiota balance and impairs short-chain fatty acid and ketone metabolism,exacerbating metabolic disturbances and aggravating hepatic injury through enhanced metabolic stress.In this article,we review the advance of studies on hypercholesterolemia in recent years and summary its association with hepatic injury,which can provide theoretical support for further research.

Objective To compare regression models for age estimation constructed based on the Pulp Dentinal Index(PDI)of the first permanent molars and explore a more accurate and applicable novel method.Methods A total of 900 Cone Beam Computed Tomography(CBCT)image datasets from adult Han Chinese individuals(455 males and 445 females)residing in Sichuan province,China,were collected from the Affiliated Hospital of North Sichuan Medical College.The PDI of the first permanent molars were measured using Mimics software.Regression analysis was performed with age as the dependent variable and PDI as the independent variable to establish and validate the optimal mathematical model for age estimation.Results Strong correlations were observed between the PDI of all four first permanent molars and age,with the correlation being stronger for maxillary teeth compared to mandibular teeth,and the highest correlation found in the left maxillary first molar among females(r=0.881).Significant differences in PDI were identified between maxillary and mandibular positions as well as between genders(P＜0.05),but not between left and right positions(P＞0.05).Among the 11 mathematical models constructed,the cubic regression model outperformed others,with the left maxillary first molar model demonstrating the best performance(Age=73.93-70.79x-68.75x2+94.33x3),yielding a mean absolute error(MAE)of 4.88 years.Conclusion Among the 11 regression models constructed in this study based on CBCT-measured PDI values of the first permanent molars,the cubic regression model exhibited the highest accuracy,with an MAE of 4.88 years.

Objective To investigate the value of amide proton transfer(APT)imaging in evaluating lymph-vascular space inva-sion(LVSI)of cervical cancer.Methods A retrospective analysis was conducted on the data of cervical cancer patients with patho-logically confirmed LVSI status.Based on the presence of LVSI,the patients were divided into LVSI positive group and LVSI nega-tive group.All patients underwent diffusion weighted imaging(DWI)and APT imaging before treatment,and the apparent diffusion coefficient(ADC)and APT values of the lesions were measured.An independent sample t-test was used to compare the differences in ADC and APT values between the two groups.The sensitivity,specificity and area under the curve(AUC)of ADC,APT and ADC+APT in predicting LVSI were observed by receiver operating characteristic(ROC)curve,and the diagnostic performance of the three was compared by DeLong test.Results A total of 78 patients were included,of which 54 were LVSI negative and 24 were LVSI positive.The ADC values in the LVSI positive group were significantly lower than those in the LVSI negative group(P＜0.001),while the APT values in the LVSI positive group were significantly higher than those in the LVSI negative group(P＜0.001).The sensitivities of ADC,APT and ADC+APT in predicting LVSI were 79.17％,83.33％ and 87.50％,respectively,the specificities were 75.93％,55.56％ and 77.78％,respectively,and the AUC were 0.828,0.759 and 0.868,respectively,indicating that the diag-nostic performance of ADC+APT was better than that of ADC and APT alone(P＜0.001).Conclusion APT imaging can preop-eratively predict the presence of LVSI status in cervical cancer.When combined with ADC,its diagnostic accuracy is higher than that of APT alone,providing a new approach for evaluating LVSI in cervical cancer.