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.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

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 understand the usage situation of e-cigarettes among residents aged 18-65 in Beijing, explore the relationship between e-cigarette use and cigarette smoking as well as smoking cessation behaviors, and provide scientific support for the developing and improving policies and measures related to e-cigarettes.Methods:Using 19 684 residents data from the Beijing Non-communication Chronic Disease and Risk Factors Surveillance in 2022, complex sampling weighted methods were used to estimate proportions, and complex sampling logistic regression analysis was applied to explore the relationship between e-cigarette use, cigarette smoking, and smoking cessation.Results:Among all study participants, the proportion of those who had ever used e-cigarettes was 3.36%, with the current e-cigarette use at 1.26%. The proportion of current e-cigarette users (1.87%) and the former e-cigarette users (3.47%) were higher ( χ2=64.70, P<0.001) among males compared to females (0.60% and 0.64% respectively). The top three reasons for using e-cigarettes were wanting to quit smoking, perceiving e-cigarettes as less harmful, and enjoying the flavors of e-cigarettes. 83.54% of e-cigarette users started with cigarettes. The results of the complex sampling multivariable logistic regression analysis showed that current smoking ( OR=61.35, 95% CI: 36.98-101.76) and former smoking ( OR=31.20, 95% CI: 15.52-62.71) were positively associated with e-cigarette, while current e-cigarette use ( OR=0.13, 95% CI: 0.04-0.39) was negatively associated with quitting cigarette smoking. Conclusions:The proportion of e-cigarette use in Beijing was relatively low. E-cigarette use was associated with cigarette use and was not conducive to smoking cessation. Therefore, stronger regulatory measures and health education campaigns regarding the risks of e-cigarettes should be implemented.

OBJECTIVE: To analyze the clinical features and laboratory characteristics of patients with cold agglutinin disease (CAD)/cold agglutinin syndrome (CAS) who were positive for acidified-serum lysis test (Ham test), and to compare them with Ham test negative CAD/CAS patients and paroxysmal nocturnal hemoglobinuria (PNH) patients, in order to provide references for the differential diagnosis of these diseases. METHODS: 53 patients diagnosed with CAD/CAS and 67 patients diagnosed with classic PNH in our hospital from January 2015 to December 2020 were retrospectively analyzed. The patients were grouped according to clinical diagnosis and results of cold agglutinin test (CAT), direct antiglobulin test (DAT), Ham test and PNH clone detection. The clinical and laboratory characteristics of each group were compared. RESULTS: The patients were grouped as follows: Ham^- CAD/CAS group, CAD/CAS patients negative for Ham test (n=36); Ham⁺ CAD/CAS group, CAD/CAS patients positive for Ham test (n=17); classic PNH group (n=67). Compared with the classic PNH group, the Ham⁺ CAD/CAS group had a higher median age (P =0.024), weaker positivity of Ham test, higher positive rates of CAT and DAT, and lower positive rate of PNH clone detection (all P <0.001). The proportions of patients with splenomegaly and cyanosis in Ham⁺ CAD/CAS group were significantly higher than those in classic PNH group (P =0.002 and P <0.001). Ham⁺ CAD/CAS group displayed lower red blood cell count (RBC) and lactate dehydrogenase (LDH) level (P =0.007 and P <0.001), and higher mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and indirect bilirubin (IBIL) level (P =0.003, P =0.004 and P =0.006) than those in classic PNH group. The levels of serum complement C3 and C4 in Ham⁺ CAD/CAS group were lower than those in classic PNH group (P =0.001 and P <0.001). The positive rate of urinary occult blood in Ham⁺ CAD/CAS group was lower than that in classic PNH group (P =0.010). The clinical and laboratory characteristics of Ham⁺ CAD/CAS group were similar to those of Ham^- CAD/CAS group, except for median age, hemoglobin (Hb), MCHC, mean corpuscular volume (MCV), reticulocyte ratio (Ret), Ham test results, DAT positive types, and proportion of splenomegaly. CONCLUSION Some clinical features and laboratory indicators of CAD/CAS patients with positive results of Ham test are different from those of classic PNH patients, but relatively similar to those of CAD/CAS patients with negative results of Ham test. These results may provide a reference for differential diagnosis of related diseases.
Humans ; Anemia, Hemolytic, Autoimmune/blood* ; Retrospective Studies ; Hemoglobinuria, Paroxysmal/diagnosis* ; Female ; Male ; Coombs Test ; Diagnosis, Differential ; Middle Aged ; Adult

OBJECTIVE: To explore the application value of joint detection of serum neutrophil-to-lymphocyte ratio (NLR), prostate-specific antigen (PSA) and MMP26 in differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH). METHODS: A total of 61 PCa patients (PCa group) and 63 BPH patients (BPH group) who were treated in The Affiliated Huaian Hospital of Xuzhou Medical University from May 2022 to May 2024 were retrospectively included. The relevant clinical data of all subjects were collected with the serum NLR, PSA and MMP26 levels being detected. Multivariate logistic regression analysis was used to analyze the influencing factors in differentiating PCa from BPH. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum NLR, PSA and MMP26 in differentiating PCa from BPH. RESULTS: The levels of TC and LDL-C in the PCa group were higher than those in the BPH group. And the level of HDL-C in the PCa group was lower than that in the BPH group (P<0.05). The serum levels of NLR, PSA and MMP26 in the PCa group were higher than those in the BPH group (P<0.05). The results of multivariate logistic regression analysis showed that NLR, PSA and MMP26 were risk factors for the diagnosis of PCa in patients (P<0.05). The ROC results showed that the area under the curve (AUC) of NLR, PSA MMP26 and joint diagnosis in the identification of PCa was 0.804, 0.800, 0.809 and 0.905, respectively. The comparison results of AUC showed that the joint diagnosis was superior to the single diagnosis (Z=2.262, 2.177, 2.002, P<0.05). CONCLUSION The joint detection of serum NLR, PSA and MMP26 has significant application value in the differentiation of PCa and BPH, which is expected to become an effective tool for early screening and diagnosis of PCa.
Humans ; Male ; Prostatic Hyperplasia/blood* ; Prostate-Specific Antigen/blood* ; Diagnosis, Differential ; Prostatic Neoplasms/blood* ; Retrospective Studies ; Neutrophils ; Lymphocytes ; ROC Curve ; Aged ; Middle Aged

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Aging and cancer share overlapping characteristics, referred to as meta-hallmarks, which elucidate the convergent, antagonistic, or contradictory relationships between aging and cancer. Likewise, as a key characteristic of aging, senescent cells share some meta-hallmarks with tumor cells. These hallmarks include apoptosis resistance, metabolic alterations, secretory phenotypes, epigenetic reprogramming, and immune surveillance, all of which play pivotal roles in both tumorigenesis and senescence. Moreover, senolytic drugs, which are a class of agents selectively designed to eliminate senescent cells, have emerged as promising therapeutic agents in oncology and aging-related diseases. Since the discovery of the first senolytic drug in 2015, a diverse array of such agents has been developed. Notably, most senolytic drugs are repurposed from existing anti-tumor therapies, leveraging their shared mechanisms with senescent cells and tumor cells. Thus, this review examines the similarities between senescent cells and tumor cells, providing a better understanding of the meta-hallmarks. Besides, we categorize existing senolytic drugs based upon meta-hallmarks and elucidate the potential molecular mechanisms underlying their effects. By integrating insights from cancer and senescence research, this work aims to inspire innovative strategies for senolytic drug discovery.