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.

AIM:To investigate the effects of electroacupuncture(EA)at"Qihai","Zhongji"and"Guanyuan"acupoints on urinary control function in rats with stress urinary incontinence(SUI)as well as to explore the mechanism of regulating ferroptosis.METHODS:A total of 50 Sprague-Dawley(SD)rats were randomly assigned to 5 groups.The rats in control(Con)group did not receive any treatment.The rats in model group was modeled for bilateral oophorectomy and vaginal dilation.The rats in EA group received EA treatment at"Qihai","Zhongji"and"Guanyuan"acupoints after modeling,while those in sham acupuncture(sham)group received EA treatment beside the specified acupoints after modeling.The rats in EA+solute carrier family 7 member 11(SLC7A11)inhibitor imidazole ketone erastin(IKE)group received an intraperitoneal injection of 50 mg/kg IKE and EA intervention after modeling.After the experiment,the uri-nary control indicators of leak point pressure(LPP),abdominal LPP(ALPP),and maximum bladder capacity(MBC)were measured for all rats.Hematoxylin-eosin(HE),Masson and Prussian blue staining was performed to observe the pathological changes and iron deposition in the urethral sphincter muscle.Enzyme-linked immunosorbent assay(ELISA)was performed to detect the mitochondrial functional indicators(mitochondrial membrane potential and ATP)and redox in-dicators:changes in the levels of reactive oxygen species(ROS),malondialdehyde(MDA),and glutathione(GSH).RT-qPCR,Western blot and immunofluorescence staining were performed to detect the expression of key iron death proteins.RESULTS:When compared with the Con group,the main urinary control indicators of MBC,LPP,and ALPP in the model group were significantly reduced(P<0.05),and the urethral sphincter fibers were broken and disordered,iron de-position was significant,and the proportion of muscle fibers was significantly reduced.The mitochondrial function indica-tors and GSH levels were significantly reduced(P<0.05),while the ROS intensity,Fe2+and MDA levels were significant-ly increased(P<0.05),the glutathione peroxidase 4(GPX4)and SLC7A11 mRNA protein expressions were significantly reduced(P<0.05),and the acyl-CoA synthetase long-chain family member 4(ACSL4)and transferrin receptor 1(TFR1)protein expressions were significantly increased(P<0.05).When compared with the model group,the main urinary con-trol indicators of the rats in the EA group were significantly improved(P<0.05).The urethral sphincter fibers breakage and disordered were attenuated,iron deposition was significantly reduced,and the proportion of muscle fibers was signifi-cantly increased.The mitochondrial function indicators and GSH levels were significantly increased(P<0.05),while the ROS intensity,Fe2+and MDA levels were significantly reduced(P<0.05).The mRNA and protein expressions of GPX4 and SLC7A11 were significantly increased(P<0.05),and the mRNA and protein expressions of ACSL4 and TFR1 were significantly reduced(P<0.05).When compared with the EA group,the above indicators in the EA+IKE group showed negative changes,and the difference was statistically significant(P<0.05).CONCLUSION:Treatment with EA at"Qi-hai","Zhongji"and"Guanyuan"acupoints improves urinary function in SUI,and the underlying mechanism may be relat-ed to ferroptosis mediated by the SLC7A11/GPX4 signaling pathway.

Purpose To investigate the role of 18F-FDG PET/CT in predicting histological grade of invasive pulmonary adenocarcinoma in the WHO(2021)classification.Materials and Methods The Clinical,pathological and PET/CT data of 255 patients with invasive pulmonary adenocarcinoma confirmed by surgical pathology were retrospectively analyzed from May 2015 to August 2023.Tertiary tumor grading was performed according to the WHO(2021)classification.The clinicopathologic features,maximum standardized uptake value(SUVmax),maximum standardized uptake,total lesion glycolysis and CT imaging findings were compared among the three tumor grades.Logistic regression analysis was used to screen the independent predictors for grade 3 tumors,and performance evaluation was performed using receiver operating characteristic curve.Results Higher tumor grade was associated with male sex(χ2=11.803,P=0.003),smoking history(χ2=7.702,P=0.021),maximum tumor diameter(H=20.548,P=0.002),lymph node metastasis(P<0.001),vascular cancer thrombus(χ2=33.270,P<0.001),pleural invasion(χ2=15.116,P=0.001)and airway spread(χ2=17.867,P<0.001).SUVmax(H=71.488,P<0.001),total lesion glycolysis(H=30.658,P<0.001)and the proportion of pure solid tumors on CT image(χ2=28.872,P<0.001)all increased significantly with higher tumor grade.A higher SUVmax(OR=1.234,95%CI 1.141-1.334,P<0.001)and pure solid appearance(OR=2.205,95%CI 1.166-4.171,P=0.015)were independent predictors of grade 3 tumors.The area under the receiver operating characteristic curve for SUVmax,CT solid appearance and the combination for predicting grade 3 tumors was 0.793,0.641 and 0.804,respectively,with the SUVmax cut-off of 6.08.Conclusion SUVmax and CT solid appearance are independent predictive factors for grade 3 invasive pulmonary adenocarcinoma.Preoperative 18F-FDG PET/CT can assist in evaluating the grading of invasive pulmonary adenocarcinoma,which improves treatment decision-making.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Purpose To investigate the role of 18F-FDG PET/CT in predicting histological grade of invasive pulmonary adenocarcinoma in the WHO(2021)classification.Materials and Methods The Clinical,pathological and PET/CT data of 255 patients with invasive pulmonary adenocarcinoma confirmed by surgical pathology were retrospectively analyzed from May 2015 to August 2023.Tertiary tumor grading was performed according to the WHO(2021)classification.The clinicopathologic features,maximum standardized uptake value(SUVmax),maximum standardized uptake,total lesion glycolysis and CT imaging findings were compared among the three tumor grades.Logistic regression analysis was used to screen the independent predictors for grade 3 tumors,and performance evaluation was performed using receiver operating characteristic curve.Results Higher tumor grade was associated with male sex(χ2=11.803,P=0.003),smoking history(χ2=7.702,P=0.021),maximum tumor diameter(H=20.548,P=0.002),lymph node metastasis(P<0.001),vascular cancer thrombus(χ2=33.270,P<0.001),pleural invasion(χ2=15.116,P=0.001)and airway spread(χ2=17.867,P<0.001).SUVmax(H=71.488,P<0.001),total lesion glycolysis(H=30.658,P<0.001)and the proportion of pure solid tumors on CT image(χ2=28.872,P<0.001)all increased significantly with higher tumor grade.A higher SUVmax(OR=1.234,95%CI 1.141-1.334,P<0.001)and pure solid appearance(OR=2.205,95%CI 1.166-4.171,P=0.015)were independent predictors of grade 3 tumors.The area under the receiver operating characteristic curve for SUVmax,CT solid appearance and the combination for predicting grade 3 tumors was 0.793,0.641 and 0.804,respectively,with the SUVmax cut-off of 6.08.Conclusion SUVmax and CT solid appearance are independent predictive factors for grade 3 invasive pulmonary adenocarcinoma.Preoperative 18F-FDG PET/CT can assist in evaluating the grading of invasive pulmonary adenocarcinoma,which improves treatment decision-making.

support the diagnosis.The treatment of PHCC is mainly based on surgery.Due to the characteristics of intact capsule,surgical resection is relatively easy and the cure rate is higher than that of ordinary hepatocellular carcinoma,and the postoperative survival rate is relatively ideal.For unresectable PHCC,palliative treatment based on transcatheter arterial chemoembolization can be used.This article reviews the progress on diagnosis and treatment of PHCC in order to provide reference for clinical practice.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.

Objective To measure and analyze anatomic parameters of resected distal femurs and proximal tibias in Kaschin-Beck disease(KBD)and osteoarthritic(OA)knees which fit for total knee arthroplasty(TKA),so as to provide basis for designing suitable knee prosthesis for KBD patients.Methods A total of 154 knees(75 KBD and 79 OA)fitting for TKA underwent three-dimensional reconstruction;resection of distal femurs and proximal tibias was simulated during TKA.We measured the distal femoral mediolateral(fML),lateral anteroposterior(fLAP),medial anteroposterior(fMAP),medial condylar width(fMCW),lateral condylar width(fLCW)and fML/fLAP aspect ratio,proximal tibial mediolateral(tML),middle anteroposterior(tAP),medial anteroposterior(tMAP),lateral anteroposterior(tLAP)dimension,and tML/tAP aspect ratio to compare the morphometric differences between KBD and OA knees.Results The measured anatomic parameters of resected distal femurs and proximal tibias in both male and female patients of KBD group were smaller than those of OA knees(P＜0.01).We also found that KBD group had larger distal femur fML/fLAP and proximal tibia tML/tAP aspect ratios than those of OA knees(P＜0.01).This indicated that under a given AP dimension,KBD knees need an oval-shaped prosthesis with a wider ML length and more spherical-shaped prosthesis with relatively narrow ML dimensions in OA knees.Conclusion The anatomy of distal femurs and proximal tibias shows significant differences in size and shape between KBD and OA knees,which provides theoretical basis for designing proper knee prosthesis for KBD patients.

Objective To observe the value of shear wave elastography(SWE)for evaluating therapeutic effect of ultrasound-guided drug injection for muscle injury.Methods Eighty patients with unilateral muscle injury were retrospectively included,including 40 cases underwent ultrasound-guided drug injection(group A)and 40 cases underwent electromagnetic wave physiotherapy plus external application of Yunnan Baiyao Gao(group B).Pain intensity was assessed using visual analogue scale(VAS)before treatment and 3 weeks after the final treatment,while the Young modulus(E)value of the injured muscle was measured before treatment and 1,2 and 3 weeks after final treatment,and the improvements of VAS scores and E values were compared between groups.Results The total effective rate in group A(35/40,87.50%)was higher than that in group B(21/40,52.50%;P＜0.05).Before treatment,no significant difference of VAS score was found between group A(8.07±0.83)and group B(7.88±0.85)(P＞0.05).After treatment,VAS scores decreased in both groups(both P＜0.05),which in group A(2.30±1.07)was more obviously than that in group B(4.80±0.82)(P＜0.05).After treatment,E values of injury muscles increased significantly in both groups(P＜0.05),while group A had a greater increase in overall magnitude and overall rate than group B(P＜0.05).Conclusion Ultrasound-guided drug injection therapy had significant therapeutic effect for muscle injuries,which could be dynamically monitored with SWE.

Objective To explore the gender differences and the influence of varus and valgus deformities on distal femur rotational alignment in patients with knee osteoarthritis so as to provide reference for the distal femur rotational osteotomy in total knee arthroplasty(TKA).Methods CT data of 125 knees with osteoarthritis suitable for TKA(including 56 males and 69 females;78 varus knees and 47 valgus knees)were collected and received three-dimensional imaging reconstruction with Mimics software.We measured the posterior condylar angle(PCA),the angle between the anteroposterior axis and the surgical epicondylar axis(ASA),and the angle between the anteroposterior axis and the posterior condylar axis(APA).We also compared gender differences and the influences of varus-valgus deformities on distal femur rotational alignments.Results The PCA and ASA values of distal femur rotational alignments were(3.5±1.1)° vs.(2.8±1.2)°(P=0.001)and(90.6±3.4)° vs.(91.9±3.5)°(P=0.028)for males and females,with statistically differences between the genders.There was no statistically difference in APA between males and females(P=0.482).The PCA values of distal femur rotational alignment in varus and valgus knees were(3.6±1.1)° and(2.9±1.2)°,with a statistically difference between the two groups(P=0.001).There were no statistically differences in ASA or APA between varus and valgus knees(P＞0.05).Conclusion Gender and varus-valgus deformities of knee joint affect the distal femur rotational alignment.Distal femur rotational osteotomy angle should be determined according to the patient's CT imaging before TKA to reduce the errors caused by individual differences and improve the accuracy of the distal femur rotational alignment during TKA.