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 construct a group-based trajectory model (GBTM) for early medication adherence check-in, and to analyze the relationship between different trajectories and treatment outcomes in tuberculosis patients using data that were generated from smart tools for monitoring their medication adherence and check-in. MethodsFrom October 1, 2022 to September 30, 2023, a total of 163 pulmonary tuberculosis patients diagnosed in Fengxian District were selected as the study subjects. The GBTM was utilized to analyze the weekly active check-in trajectories of the subjects during the first 4 weeks and establish different trajectory groups. The χ² tests were employed to compare the differences between groups and logistic regression analysis was conducted to explore the relationship between different trajectory groups and treatment outcomes. ResultsA total of four groups were generated by GBTM analyses, of which a low level of punch card was maintained in group A, 6% of the drug users increased rapidly from a low level in group B, 17% of drug users increased gradually from a low level in group C, and 18% of drug users maintained a high level of punch card in group D. The trajectory group was divided into two groups according to homogeneity, namely the low level medication punch card group (group A) and the high level medication punch card group (group B, group C, and group D). The results of multivariate logistic regression analyses revealed that low-level medication check-in (OR=3.250, 95%CI: 1.089‒9.696), increasing age (OR=1.030, 95%CI: 1.004‒1.056), and not undergoing sputum examination at the end of the fifth month (OR=2.746, 95%CI: 1.090‒7.009) were significantly associated with poor treatment outcomes. ConclusionThe medication check-in trajectory of pulmonary tuberculosis patients within the first 4 weeks is correlated with adverse outcomes, or namely consistent low-level medication adherence check-ins are associated with poor treatment outcomes, while high-level medication adherence check-ins are associated with a lower incidence of adverse outcomes.

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.

The S100 protein family is a key component of damage-associated molecular patterns(DAMP), which play a vital role in regulating inflammation in the body's innate immune response. S100A8/S100A9 proteins play a wide range of antibacterial and anti-infective functions in many diseases, and promote the occurrence and development of the body's immune and inflammatory responses. In various retinal degenerative diseases, S100A8/S100A9 proteins are significantly upregulated at the transcription and translation stages, promoting the activation of inflammatory factors in ocular tissues, the activation and recruitment of immune cells such as macrophages and neutrophils, and the occurrence and development of ocular inflammation. This review aimsat explaining the biological functions of S100A8/S100A9 proteins and their roles and possible mechanisms in retinal degenerative diseases such as diabetic retinopathy, age-related macular degeneration and ischemic retinopathy.

Objective To provide references,this study investigated the clinical characteristics of patients with non-syndromic oligodontia.Methods The information of 178 patients with oligodontia was collected,including histories,oral examinations,and panoramic radiographs.Tooth agenesis characteristics were calculated and evaluated.All the data were statistically analyzed with SPSS 24.0 software.Results No significant difference in the number of missing teeth was found between sexes nor between the right and left sides,and congenitally missing teeth affected the maxillary arch(P<0.05).The highest prevalence of tooth agenesis was observed in the mandibular second premolars.In the maxillary arch,the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars.The agenesis of the bilateral second premolars was observed in the mandibular arch.The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular an-tagonistic quadrants.Approximately 16.85%of patients with nonsyndromic oligodontia were affected by other tooth-re-lated anomalies.Conclusion The common patterns of tooth agenesis were successfully identified in patients with non-syndromic oligodontia.Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.

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.

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal

Objective:To investigate the changes in structural brain network topology and microstructural damage in patients with multiple sclerosis (MS), and to analyze its correlation with cognitive function.Methods:Clinical and imaging data of 114 patients with MS (MS group) diagnosed in the First Affiliated Hospital of Chongqing Medical University from May 2021 to September 2022 were analyzed retrospectively. In addition, 71 volunteers were recruited as a healthy control group (HC group) during the same period. All subjects were performed on cognitive assessment and 3D-T 1 magnetization-prepared rapid gradient echo, 3D-fluid-attenuated inversion recovery, and diffusion kurtosis imaging (DKI) scans. GRETNA software was used to obtain network topology attributes, and global attributes included global efficiency, local efficiency, and small-world attributes [clustering coefficient(Cp), shortest path length(Lp), normalized Cp(γ), normalized Lp, and small-world index (σ)]. Local attributes included betweenness centrality (BC), degree centrality (DC), nodal clustering coefficient (NCp), nodal efficiency, nodal local efficiency (NLe) and nodal shortest path length. The DKI parameter map generated by the post-processing software was used to extract the DKI parameter values of the brain region with abnormal local topology of the brain structure network. The differences of global attributes, local attributes and DKI parameter values [kurtosis fractional anisotropy (KFA), mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) values] were analyzed by independent sample t-test or Mann-Whitney U test, and corrected by false discovery rate (FDR). Spearman or Pearson correlation analysis was used to evaluate the correlation between abnormal brain structure network topology attributes and cognitive scale scores in the MS group. Results:Both the MS group and the HC group structure network showed small-world attributes, and the γ and σ values of the MS group were significantly lower than those in the HC group (FDR correction, P<0.05). Compared with the HC group, BC, DC, NCp and NLe broadly reduced in the MS group, mainly involving in bilateral frontal, temporal, precuneus, amygdala, and thalamus (FDR correction, P<0.05). After FDR correction, compared with the HC group, the KFA, MK, RK and AK values of 23 brain regions with abnormal local attributes of the network in the MS group were significantly changed in several brain regions (FDR correction, P<0.05). The correlation analysis showed, after FDR correction, the DC value of the right putamen in MS patients was positively correlated with the digit span test (DST) scores ( r=0.318 ,P=0.001). Conclusion:There are extensive changes in the structural brain network of MS patients, accompanied by varying degrees of microstructural damage, and the reduction of degree centrality in the basal ganglia putamen region is associated with cognitive impairment.

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8⁺ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8⁺ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

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.