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.

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 construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

AIM:To explore the therapeutic effect of Tongfeng-Qingli mixture(TFQLM)and its mechanism in hyperuricemic(HUA)rats based on uric acid(UA)transporter and Janus kinase 2(JAK2)/signal transducer and acti-vator of transcription 3(STAT3)signaling pathway.METHODS:(1)In vivo experiment:36 male SD rats were random-ly divided into control(CON)group,model(MOD)group,benzbromarone(BEN)group,low-dose TFQLM(TFQLM-L)group,medium-dose TFQLM(TFQLM-M)group,and high-dose TFQLM(TFQLM-H)group,with 6 rats in each group.In all groups except CON group,HUA was induced in rats by giving hypoxanthine(HP)combined with potassium oxybate(OP)for 35 consecutive days.The rats in CON group were given sodium carboxymethyl cellulose solution by gavage.A fully automatic biochemistry analyzer was used to detecte serum UA,serum creatinine(SCr)and blood urea nitrogen(BUN)levels.The xanthine oxidase(XOD)and adenosine deaminase(ADA)levels in the liver were detected by ELISA kits.The histopathological changes of kidneys were observed by HE staining.Immunohistochemistry was performed to de-tect urate transporter 1(URAT1)and glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and OAT3 ex-pression in the kidney.Western blot was used to measure the protein levels of URAT1,GLUT9,OAT1,OAT3,interleu-kin-6(IL-6),tumor necrosis factor-α(TNF-α),JAK2,p-JAK2,STAT3,p-STAT3 and repressor of cytokine signaling 3(SOCS3)in the kidney.(2)In vitro experiments:HUA cellular model was established by UA stimulation in HK2 cells,and the protein levels of URAT1,GLUT9,OAT1,OAT3,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3,and SOCS3 were detected by Western blot.RESULTS:Compared with MOD group,serum UA,SCr and BUN levels of the rats in all TFQLM groups were reduced(P<0.05).The XOD and ADA levels in liver tissues were significantly reduced(P<0.05).The protein levels of URAT1,GLUT9,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were decreased(P<0.05),and OAT1 and OAT3 protein expression was increased(P<0.05)in kidneys and HK2 cells.CONCLUSION:By establishing rat and HK2 cell HUA models,it is hypothesized that TFQLM may reduce UA levels and attenuate renal inflammation in HUA rats,and its mechanism may be related to the regulation of UA transport proteins and inhibition of the JAK2/STAT3 signaling pathway.

Objective:To explore the risk factors for recurrence of thyroid cancer after radical resection via areola endoscopy,and to construct a visual risk prediction model.Methods:The clinical data of 350 thyroid cancer patients who underwent radical surgery via areola endoscopy in our hospital from January 2016 to October 2018 were retro-spectively analyzed,and they were randomly divided into the modeling group(233 cases)and the internal validation group(117 cases)in a 2:1 ratio.All patients were followed up for 3 years after surgery,and the patients of modeling group were further divided into recurrent group(51)and non recurrent group(182)according to whether they with or not recurrence.Another 163 patients with thyroid cancer who underwent laparoscopic radical mastectomy at our hos-pital from January 2019 to May 2020 were selected as the external validation group.The risk factors for recurrence of thyroid cancer after radical surgery via areola endoscopy was analyzed by using Cox regression method,and a risk prediction nomogram model was established based on this.Internal validation of the nomogram model was conducted by using the Bootstrap method,and the calibration,predictive efficacy and clinical net benefit of the nomogram model were evaluated by the calibration curve,receiver operating characteristic(ROC)curve and decision curve analysis(DCA).The external validation group data was used for external validation.Results:The recurrence rate of thyroid cancer patients after 5 years of radical surgery via areola endoscopy was 21.64％(111/513).The proportions of multiple le-sions,preoperative lymph node metastasis,TNM stages Ⅲ-Ⅳ and maximum tumor diameter,the levels of thyro-globulin(TG),triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),free thyroxine(FT4)and thyroid stimulating hormone(TSH)in the recurrence group were higher than those in the non recurrence group(P<0.05).The Cox regres-sion analysis results showed that the maximum tumor diameter,multiple lesions,preoperative lymph node metasta-sis,TNM stage Ⅲ-Ⅳ and TG,T3,T4,FT3,FT4 and TSH levels were all risk factors for recurrence of thyroid cancer after radical surgery via areola endoscopy(P<0.05).The risk prediction nomogram model of recurrence of thyroid cancer af-ter radical surgery under areola endoscopy was constructed based on the above influencing factors.After internal and external validation,the consistency indices of the modeling group,internal verification group and external verification group were 0.832,0.825 and 0.41 respectively,and the calibration curves of three groups were close to the standard curve.The ROC curve analysis and verification showed that the area under the curve predicted by the nomogram model of the modeling group,internal verification group and external verification group were 0.859,0.847 and 0.853 respectively.The DCA curve showed that the nomogram model had good clinical net benefits when the threshold probability of the modeling group,internal verification group and external verification group were 0.03-0.82,0.02-0.78 and 0.06-0.88 respectively.Conclusion:The maximum tumor diameter,multiple lesions,preoperative lymph node metastasis,TNM staging stage Ⅲ-Ⅳ and levels of TG,T3,T4,FT3,FT4 and TSH are all risk factors for recurrence of thy-roid cancer after radical surgery via areola endoscopy,and the risk prediction visualization nomogram model con-structed based on this is helpful for clinical screening of high-risk patients to guide early intervention and reduce the risk of recurrence.

Objective:To analyze the clinical characteristics and treatment outcomes of children with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody-mediated necrotizing myopathy, and to explore early identification and management strategies to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data and treatment outcomes of 10 pediatric patients with anti-HMGCR antibody-mediated necrotizing myopathy admitted to the Department of Rheumatology, Children′s Hospital of Fudan University from December 2020 to December 2024. Statistical description was performed using SPSS 22.0.Results:Among the 10 patients, the male-to-female ratio was 1:4, the age of onset was (7.2±4.0) years, and the disease duration at diagnosis was (22.2±19.6) months. None had a history of statin exposure. Six patients presented with muscle weakness, and4 were diagnosed due to asymptomatic elevation of creatine kinase (CK); 4 had dermatomyositis-like rashes. All patients showed significantly elevated CK levels [median 3 291(1 969, 8 776)U/L] and underwent muscle biopsy. Histopathological findings revealed myofiber degeneration, necrosis, and regeneration in all cases, with inflammatory infiltration in 9 cases, MHC-Ⅰ positivity in all, and C5b-9 positivity in 9 cases. The median follow-up duration was (15.7±6.3) months. At the last follow-up, muscle strength was normal or nearly normal, and the CK median value had decreased to 977.5 (211.0, 3 536.0) U/L.Conclusion:For patients with suspected idiopathic inflammatory myopathy and significantly elevated CK, muscle-specific antibody testing-including anti-HMGCR-and muscle biopsy should be performed promptly regardless of the presence of skin rash, to ensure accurate diagnosis and guide treatment, thereby avoiding misdiagnosis or missed diagnosis.

To establish a rapid Akabane virus(AKAV)antibody detection method in animals,the re-combination AKAV N protein was expressed by the expression system of Escherichia coli,puri-fied from the supernatant,and used to immunized New Zealand White rabbits.The polyclonal anti-body against AKAV N protein had a titer of 1∶8.192×107 and showed good reactivity.After opti-mizing the reaction conditions,an AKAV double antigen sandwich ELISA antibody detection method was established.This method can detect AKAV antibody in a variety of animals including cattles,sheep and goats.The method had no cross-reactivity with the positive serum of BTV,EHDV,BEV and PRV with the intra-and inter-batch coefficients of variation less than 10％.Com-pared with the AKAV blocking ELISA kit,the sensibility of the method was increased by 8-16 folds with a compliance rate of 93.33％and the κ value of 0.864.These results showed that the double antigen sandwich ELISA displayed strong specificity,high sensitivity and repeatability,which could provide technical suport for detection,the prevention and control of AKAV.

To establish a rapid Akabane virus(AKAV)antibody detection method in animals,the re-combination AKAV N protein was expressed by the expression system of Escherichia coli,puri-fied from the supernatant,and used to immunized New Zealand White rabbits.The polyclonal anti-body against AKAV N protein had a titer of 1∶8.192×107 and showed good reactivity.After opti-mizing the reaction conditions,an AKAV double antigen sandwich ELISA antibody detection method was established.This method can detect AKAV antibody in a variety of animals including cattles,sheep and goats.The method had no cross-reactivity with the positive serum of BTV,EHDV,BEV and PRV with the intra-and inter-batch coefficients of variation less than 10％.Com-pared with the AKAV blocking ELISA kit,the sensibility of the method was increased by 8-16 folds with a compliance rate of 93.33％and the κ value of 0.864.These results showed that the double antigen sandwich ELISA displayed strong specificity,high sensitivity and repeatability,which could provide technical suport for detection,the prevention and control of AKAV.

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

OBJECTIVE: To study the clinical effects of pomalidomide-based regimen in the treatment of relapsed and refractory multiple myeloma (RRMM). METHODS: 60 patients with RRMM in hematology department of the First Affiliated Hospital of Xinxiang Medical University from November 2020 to January 2023 were selected. Among them, 15 cases were treated with PDD regimen (pomalidomide + daratumumab + dexamethasone), and 45 cases were treated with PCD regimen (pomalidomide + cyclophosphamide + dexamethasone). The clinical effects were evaluated. RESULTS: The median number of treatment cycles for the entire cohort was 5 (2-11), with an overall response rate (ORR) of 75.0%. The ORR of patients treated with PDD regimen was 73.3%, while the ORR of patients treated with PCD regimen was 75.6%. The ORR of 46 patients with non high-risk cytogenetic abnormalities (non-HRCA) was 86.9%, significantly higher than the 35.7% of 14 patients with HRCA (χ² =15.031, P < 0.05). The median PFS for all patients was 8.0(95%CI : 6.8-9.1) months and the median OS was 14.0 (95%CI : 11.3-16.7) months. Among patients treated with PDD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 7.0(95%CI : 4.6-9.3) months vs 4.0(95%CI : 3.1-4.8) months, χ² =5.120, P < 0.05; OS: not reached vs 6.0(95%CI : 1.1-10.9) months, χ² =9.870, P < 0.05]. Among patients treated with PCD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 9.0(95%CI : 6.2-11.8) months vs 6.0(95%CI : 5.4-6.6) months, χ²=14.396, P < 0.05; OS: not reached vs 11.0(95%CI : 6.4-15.6) months, χ² =7.471, P < 0.05]. CONCLUSION The pomalidomide-based regimen has a good clinical effect and safety in the treatment of RRMM.
Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/administration & dosage* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Middle Aged ; Recurrence ; Aged ; Cyclophosphamide/therapeutic use* ; Treatment Outcome ; Antibodies, Monoclonal