BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P＜0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P＞0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

【Objective】 To analyze the sensory integration characteristics of 4- to 5-year-old preschool children while maintaining static balance, in order to provide reference for promoting the development of motor development. 【Methods】 A total of 128 preschool children were randomly selected in this study from a public kindergarten in Suzhou. Wearable sensor were worn at the center of mass(COM) position for four tests: T1 standing with eyes open, T2 standing with eyes closed, T3 standing with eyes open on a sponge pad, and T4 standing with eyes closed on a sponge pad. The angular velocity modulus(ω) of COM shaking was extracted, the Romberg quotient(RQ), vestibular Romberg quotient(VRQ), and the rate of increase in body stability when integrating different sensations were calculated. The contribution weights and sensory integration characteristics of visual, proprioceptive, and vestibular sensations to static balance were analyzed. Independent sample t-test was used to analyze the differences between different gender and age groups. 【Results】 The RQ was 1.20, and the VRQ was 1.58. The contribution rates of visual, proprioceptive, and vestibular senses to body balance were approximately 9.28%, 28.19% and 62.53%, respectively. The difference in the rate of increase in body stability between integrated vision and integrated proprioception with normal vestibular perception was statistically significant(P<0.001, Cohen′s d=-1.14),while the difference in the rate of increase in body stability between integrated proprioception and vestibular perception with normal vestibular perception and integrated vision with normal proprioception was statistically significant(P<0.001, Cohen′s d=2.30). The difference in the rate of increased body stability between the sum of vestibular and proprioceptive integration and the simultaneous integration of visual and proprioceptive integration was statistically significant(P<0.001, Cohen′s d=-0.86). The gender differences in RQ, VRQ, and the rate of increased body stability when integrating different sensations(P>0.05) and the difference in half year old age was not statistically significant(P>0.05). 【Conclusions】 When preschool children aged 4 - 5 maintain static balance, the contribution of vestibular integration proprioception to body stability is greater than that of vestibular integrate vision. The contribution of vestibular and visual integrate proprioception to body stability is greater than that of vestibular and proprioception integrate vision. The sensory integration characteristics between boys and girls, as well as half year old children, are basically the same.

Objective To analyze medication rules of traditional Chinese medicine in the treatment of thyroid nodules based on real-world data mining technology. Methods Chinese medicine prescriptions for patients with thyroid nodules as clinical first diagnosis in the Department of Thyroid and Breast Surgery in Qingdao Hospital of Traditional Chinese Medicine from August 2018 to August 2023 were collected, and the Traditional Chinese Medicine Inheritance Assistant Platform (V3.0) was used to analyze the medication rules. Results A total of 1 206 traditional Chinese medicine prescriptions for the treatment of thyroid nodules were screened, involving 291 traditional Chinese medicines; the top five most frequently used drugs were Fritillaria thunbergii, Prunella vulgaris, Bupleurum chinense, Poria cocos, and Pinellia ternata; the main function of drugs were clearing heat, tonifying deficiency, resolving phlegm, activating blood circulation, and regulating qi; the main property of the drugs was cold, the main tastes of drugs were bitter, sweet and spicy, and the meridians involved were mainly the lung, liver and spleen meridians; association rule analysis identified 17 high-frequency drug combinations, with Fritillaria thunbergii-Prunella vulgaris as the most frequently occurring drug pair; among the 16 association rules, Radix Scrophulariae-Fritillaria thunbergii and Rhizoma Cyperi-Bupleurum chinense had the highest confidence level; clustering analysis found 6 core drug combinations. Conclusion The main idea of clinical treatment of thyroid nodules in traditional Chinese medicine is to resolve phlegm and reduce nodules, promote qi circulation and blood circulation, and nourish qi and blood; the common herbal combination of Fritillaria thunbergii and Prunella vulgaris is used to clear heat, resolve phlegm, and reduce nodules, and the basic formula for resolving scrofula is based on Xiaoluo Pills, which resolves phlegm, softens hardened nodules, and reduces nodules.

Object:To explore the clinical effect of periacetabular osteotomy (PAO) in the treatment of developmental dysplasia of hip (DDH).Methods:The clinical data of 305 patients with DDH admitted to Tangshan Second Hospital from January 2012 to June 2018 were analyzed retrospectively. All patients were treated with PAO alone. There were 123 cases of left hip dysplasia, 131 cases of right hip dysplasia and 51 cases of double hip dysplasia (356 hips in total). The patients underwent X-ray examination before and on the second day after operation to compare the acetabular index and the lateral center edge angle (LCEA) and the anterior center edge angle (ACEA) of the acetabulum before and after operation. The ability of daily living and hip joint function were evaluated before and 6 months after operation, and Barthel index and Harris score of hip joint were compared before and after treatment. The measurement data with normal distribution are expressed in xˉ± s, and the paired t test was used for comparison before and after operation. The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison before and after surgery is performed by the rank sum test. Results:On the second day after operation, the LCEA and ACEA of 356 hip joints in 305 patients were greater than those before operation (32.5(20.0,47.5)° vs 8.5(-18.5 23.0)°, 29.0(18.5,52.3)° vs 2.5(-20.8, 24.5)°), while the acetabulum index was lower than that before operation (6.7(-8.4,12.5)° vs 26.8(10.0, 62.3)°), and the differences were statistically significant ( Z values were 51.50, 45.37, 32.22, all P<0.001). After 6 months of follow-up, the Barthel score and Harris score of the hip joint were higher than those before the operation (92.5±1.3) scores vs (65.6±1.5) scores, (96.4±2.5) scores vs (85.1±1.3) scores, and the difference was statistically significant ( t values were 335.56 and 89.70, both P<0.001). Conclusions:PAO can make the acetabulum cover the femoral head well through acetabular transposition, improve the ability of daily living and hip joint function of DDH patients, reduce pain, increase joint range of motion, and correct limb deformities. It is an effective means to treat DDH.

CircRNA is a single-stranded, covalently closed non-coding RNA, whose mechanism mainly involves sponge adsorption of micro RNA (miRNA), regulation of protein transcription and post-transcriptional levels, interaction with RNA-binding proteins and few coding proteins of circRNA. Meanwhile, because of its abundant expression, highly conserved and dynamic changes, circRNAs have promising applications such as becoming biomarkers of diseases, developing circRNA vaccines and gene editing therapies for circRNAs. Cardiovascular diseases are the leading cause of death from diseases worldwide, and existing therapeutic approaches can delay the development of heart diseases, but are still limited by the unknown pathogenesis and therapeutic targets. Many studies have reported the mechanistic link between circRNAs and cardiac diseases, therefore, this review is to explain the progress of circRNA research in cardiovascular diseases and to illustrate the three clinical applications in which circRNAs are currently involved.

Objective To construct pET21a-sBAFF by cloning the extracellular regions of 134-285 amino acids of BAFF, a member of human TNF family, and then express the gene in prokaryotic cells and purify the expressed product.Methods cDNA of K562 cell line was used as the template to amplify sBAFF gene to construct pET21a-sBAFF.Expression of sBAFF in E.coli BL21 was induced by IPTG, and the expressed proteins were assayed by SDS-PAGE.The bacteria were analyzed by sonication, and the target proteins mainly existed as inclusion bodies.Then sBAFF was purified by Ni2 +-IDA affinity chromatography.SDS-PAGE electrophoreses displayed that the expressed sBAFF migrated with a relative molecular weight of 18000.ResuIts The induction parameters such as temperature and inducing time were optimized.The target protein accounted for 38.59%of the total bacterial proteins.After refolding, 38.14% of sBAFF proteins were polymerized as an active trimer.The dimer form of sBAFF, which is representative of wrongly refolded product, accounted for very few.ConcIusion The expression and purification of BAFF which formed active trimer after refolding pave the way for its further function study and provide a novel approach for the development of BAFF-targeted therapeutics for autoimmune diseases.

Objective To synthesize 99Tcm-TP5-3 and evaluate its biodistribution and kinetics as a molecular probe for the detection of apoptosis,and evaluate tumor apoptosis after a single dose of paclitaxel chemotherapy in MDA-MB-231 breast tumor model.Methods TP5-3 was labeled with 99Tcm directly,and analyzed with HPLC.The radioactivity in tissues was measured and expressed as ％ID/g and T/NT (tumor/muscle).The mice bearing MDA-MB-231 breast tumor were divided into two groups:the treatment group which was given a single dose of paclitaxel (40 mg· kg-1,via tail vein),and the control group which was injected with the same volume of normal saline.After therapy,99Tcm-TP5-3 was injected via tail vein in both groups (100 μ1 for each mouse).MicroSPECT/CT was performed at 3 h postinjection.Radioactivity in different tissues was determined after imaging.Apoptotic cells were measured with flow cytometry.The morphological changes of the apoptotic cells were observed by light microscopies.One-way analysis of variance,two-sample t test and linear correlation analysis were used to analyze the data.Results The radiolabeling efficiency was ＞ 95％ and the radiochemical purity of 99Tcm-TP5-3 was (96.0± 1.5)％ at room temperature for 4 h.The predominant uptake was found in the kidneys at 30 min postinjection ((8.48± 1.07) ％ID/g),with rapid tracer clearance from the circulation.By comparison with activity at 5 min postinjection ((13.74± 4.21) ％ID/g),85％ of the initial activity reduced in blood at 4 h ((2.07±0.35) ％ID/g; F=11.310,P＜ 0.05).99Tcm-TP5-3 was mainly accumulated in the kidneys,liver and stomach,and excreted via the kidneys.T/NT in the treated group was 4.21±0.06,which was significantly higher than that of the control group (1.57±0.67; t =12.820,P＜0.05).The radioactivity of tumor tissue in the treatment group was much higher than that in the control group (4.82±0.54) ％ID/g vs (1.44±0.38) ％ID/g,t=0.679,P＜0.05).The tumor uptake of 99Tcm-TP5-3 in the treatment group positively correlated well with the apoptotic cells (r =0.985,P＜0.05).Histopathology further confirmed that a large number of apoptosis had occurred in the tumor after paclitaxel treatment.Conclusion 99Tcm-TP5-3 appears to have potential to be a useful molecular probe for imaging tumor cell apoptosis.

Objective:To study the biological characteristics of condylar chondrocytes isolated from mechanical stress stimulated TMJ condylar cartilage of rats.Methods:The rat models of mechanical stress stimulated condylar cartilage were made by class III orthope-dic force for 14 days.The cartilage from control and experimental rats were observed in gross view.The cell harvest rate and viability were examined,proteomic analysis was performed.Results:After stress stimulation the thickness,the elasticity of condylar cartilage and number of chondrocytes were significantly reduced.The weight of mandibular cartilage was decreased(P<0.01).The harvest rate and the viability rate of the cells were decreased(P<0.01).The chondrocytes in the experimental group appeared to be elongated. Proteomic analysis showed that stress-related proteins,signal transduction proteins were up-regulated;cytoskeleton proteins,cell prolif-erative proteins were down-regulated.Conclusion:Mechanical stress stimulation of condylar cartilage may result in biological activity and protein changes of the condylar cartilage chondrocytes.