Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To investigate the relationship of neutrophil to lymphocyte ratio (NLR) and homocysteine (Hcy) with risk of coronary artery lesion progression in patients with hypertension. Methods The data of 306 patients with hypertension who received coronary angiography from January 2020 to January 2025 were included for retrospective investigation. The patients were divided into a non-progression group (175 cases) and a progression group (131 cases) based on the 6-month Gensini progression rate. The relationship between NLR and Hcy and coronary artery lesion progression was analyzed. Results Binary logistic regression analysis was applied to control confounding factors. After adjusting for confounding factors using Model1, Model2, and Model3, it was found that NLR and Hcy at admission were independently associated with the progression of coronary artery lesion in hypertensive patients [adjusted OR (95% CI) = 1.77 (1.48-2.11), 4.26 (2.71-6.69), P<0.001]. Receiver operating characteristic (ROC) curve revealed that the area under the curve of the combination of Hcy and NLR was 0.814 in predicting the progression of coronary artery lesion in hypertensive patients, which was higher than that of Hcy or NLR (Z/P=5.328, 2.077/<0.05). Conclusion Cardiovascular disease risk factors NLR and Hcy are independently associated with coronary artery lesion progression in patients with hypertension. Early detection of NLR and Hcy is helpful to predict the progression of coronary artery lesion.

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.

ObjectiveTo evaluate the effects of modified Baohe Pill （保和丸） formula added to conventional pulmonary rehabilitation on thoracic drainage volume， chest tube duration， and peripheral blood inflammatory indices after video-assisted thoracoscopic surgery （VATS） for lung cancer. MethodsIn this randomized parallel-controlled study， 118 post-VATS patients were enrolled， with 59 cases in each group. The control group received conventional pulmonary rehabilitation， while the treatment group additionally received an oral decoction of modified Baohe Pill formula until chest tube removal and discharge. The primary outcome was total postoperative thoracic drainage volume， while the secondary outcomes included chest tube duration and inflammatory indices including the pre-treatment and post-treatment levels and relative changes in platelet-to-lymphocyte ratio （PLR）， neutrophil-to-lymphocyte ratio （NLR）， lymphocyte-to-monocyte ratio （LMR）， systemic immune-inflammation index （SII）， aggregate index of systemic inflammation （AISI）， and systemic inflammation response index （SIRI）. Adverse events during the treatment period were recorded. ResultsThe total postoperative thoracic drainage volume was 850 （430， 1410） ml in the treatment group， lower than 1085 （660， 1720） ml in the control group （P＜0.05）. Total postoperative chest tube duration was 8 （6， 11） days in the treatment group， shorter than 10 （7， 11） days in the control group （P＜0.05）， whereas the interval from enrollment to removal did not differ significantly between groups （P＞0.05）. The postoperative NLR in the treatment group was lower than that in the control group， and the relative change in NLR was greater than that in the control group （P＜0.05）. No significant between-group differences were found in post-treatment levels or relative changes of the other five inflammatory indices （P＞0.05）. No treatment-related serious adverse events were reported in either group. ConclusionModified Baohe Pill formula plus conventional pulmonary rehabilitation has lower total postoperative thoracic drainage volume， shorter total postoperative chest tube duration， and lower NLR levels in lung cancer patients following VATS， while demonstrating a more favorable safety profile than conventional pulmonary rehabilitation alone.

AIM:This study aimed to investigate the protective effects of Carthamus tinctorius L.-derived nanovesicles(CDNVs)and their regulatory mechanisms in endothelial cell injury induced by oxidized low-density lipopro-tein(ox-LDL).METHODS:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and subjected to ox-LDL treatment to establish an endothelial cell injury model.The experimental groups included the normal control(NC)group,ox-LDL group(HUVECs treated with 100 mg/L ox-LDL for 24 h),and CDNVs+ox-LDL group(pre-treated with 40 mg/L CDNVs for 1 hour followed by co-culture with 100 mg/L ox-LDL for 24 hours).Cell proliferation and apoptosis were assessed by the EdU incorporation assay and flow cytometry,respectively.Changes in signal-induced proliferation-associ-ated 1-like protein 2(SIPA1L2)mRNA expression were measured by RT-qPCR,and the expression levels of autophagy-related proteins and SIPA1L2 were evaluated by Western blot.SIPA1L2 ubiquitination was evaluated by immunoprecipita-tion assay.RESULTS:(1)CDNVs were successfully isolated and purified,characterized as nanoscale vesicles with a circular shape and a double-layered membrane structure.(2)CDNVs promoted the proliferation and inhibited apoptosis of ox-LDL-treated HUVECs(P＜0.05).(3)CDNVs suppressed the prorein expression of SIPA1L2 and promoted autophagy in ox-LDL-treated HUVECs(P＜0.05).(4)CDNVs facilitated the ubiquitination of SIPA1L2 protein,and reduced its protein level through the ubiquitin-proteasome pathway(P＜0.05).CONCLUSION:CDNVs exert a protective effect against ox-LDL-induced endothelial cell injury by mediating SIPA1L2 ubiquitination and promoting endothelial cell au-tophagy.

Objective To systematically review the evidence from systematic reviews on the effect of exercise on internet behavioral addictions.Methods Systematic reviews on exercise for internet behavioral addictions were searched in Web of Science,Scopus,EBSCO,PsycINFO,PubMed,Cochrane Library,Embase and CNKI,from January,2015 to January,2025.In ac-cordance with the PRISMA guidelines,the evidences about exercise on internet behavioral addiction,as well as the health benefits,were reported.Results Eleven English reviews were included,from China,Malaysia,Indonesia and Australia,involving 31 672 internet behavioral addiction aged ten to 30 years,covering internet addiction,mobile phone addiction and gaming addic-tion.The included literatures were all systematic reviews mainly from journals in psychology,psychiatry,public health,etc.Interventions included aerobic exercise,strength training,functional training,skill-based training and structured combination exercise,with programs ranging from 30 to 120 minutes per session,one to six times per week,for six to 24 weeks.Exercise significantly improved mental health,behavioral health,physical health and cognitive function.Moderate-intensity structured combination exercise(≥60 minutes persession,≥3 times per week,≥8 weeks)showed the best outcomes,especially for gaming addiction.Exercise combined with psycholog-ical therapy was more effective for severe addiction.Conclusion Exercise is effective on internet behavioral addictions,and moderate-intensity structured combination exer-cise is the most effective.It is recommended to use structured combination exercise for gaming addiction and combined exercise-psychological therapy for severe addiction.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Purpose To explore the clinicopathological features of EBV-positive nodal T-and NK-cell lymphoma.Methods Clinical and pathological data of 5 cases were collected.The expression of CD3,CD56,TIA-1,Granzyme B and other markers were detected by immunohistochemistry.The expression of EBER was detected by in situ hybrid-ization.The gene rearrangement and clonality were analyzed by PCR and polyacrylamide gel electrophoresis.The litera-tures were reviewed.Results The primary lesions of the 5 patients were all located in lymph nodes.All patients pres-ented with multiple lymphadenopathy,B symptoms,elevated lactate dehydrogenase(LDH)and C-reactive protein(CRP),and were in stage Ⅲ/Ⅳ.Histopathologically,the lesions show a diffuse infiltration of large to medium monot-onous tumor lymphocytes.Cell apoptosis,necrosis,and vascular invasion were not significant.Tumor cells of all cases were positive for CD3 but negative for CD56.All cases were positive for the cytotoxic markers.In situ hybridization de-tection showed that the majority of tumor cells were diffusely positive for EBER.Nevertheless,only 4 cases were posi-tive for TCR gene clonal rearrangement.Three patients received chemotherapy,2 patient declined the treatments.The median overall survival was only 3 months.Conclusions EBV-positive nodal T-and NK-cell lymphoma is an EBV-positive lymphoma of cytotoxic T-or NK-cell lineage presenting primarily with nodal disease,which is more common in elderly males.The patient has obvious symptoms and signs,rapid disease progression,and poor prognosis.Under-standing the clinicopathological features of EBV-positive nodal T-and NK-cell lymphoma can help differentiate it from other EBV-positive T-and NK-cell lymphoid proliferations and lymphomas.

Objective:To investigate the effect of monocular form deprivation (MD) on the distribution density of neuregulin-1 (NRG1) + and NRG1 - parvalbumin (PV) neurons in the primary visual cortex of mice during the critical period of visual development. Methods:Twelve healthy 28-day-old SPF male C57BL/6J mice were randomly divided into control group and MD group by the random number table method, with 6 mice in each group.After MD on postnatal day (P) 28, the MD group was fed until P32, while the control group was fed normally until P32.All mice were sacrificed by cervical dislocation after cardiac perfusion, and brain tissues were quickly collected.After fixation overnight, brain slices were subjected to PV and NRG1 immunofluorescence staining to observe and compare the differences in the distribution density of PV + , PV + /NRG1 + and PV + /NRG1 - neurons in both sides of the primary visual cortex (V1) area of the two groups.This study was conducted in accordance with the Regulations on the Administration of Experimental Animals (2017 Revision), and the study protocol was approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (No.TMUaMEC2022004). Results:Immunofluorescence staining showed that the density of PV + and PV + /NRG1 + neurons was (137.8±4.3), (108.8±4.1), (137.4±4.0)/mm 2 in the contralateral V1 area of the control group, MD group and the ipsilateral V1 area of the MD group, and that of PV + /NRG1 + neurons was (112.0±4.6), (82.1±4.7) and (113.6±5.7)/mm 2, respectively, with statistically significant overall differences ( F=15.88, 12.53; both P<0.001).PV + neuron density and PV + /NRG1 + neuron density in the contralateral V1 area of the MD group were significantly lower than in the control group and in the ipsilateral V1 area of the MD group (all P<0.001).There was no difference in PV + /NRG1 - neuron density between the two groups ( F=0.20, P>0.05). Conclusions:PV + /NRG1 + neurons may be the main cell type regulating the development of primary visual cortex during the critical period.