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.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

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.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Objective:To investigate the effect of Tongguan Fang drug-containing serum on LPS-induced inflammation of RAW264.7 cells,so as to clarify the cellular mechanism of the Tongguan Fang in treating tubal inflammatory infertility.Methods:Lipo-polysaccharide(LPS)was used to stimulate the RAW264.7 macrophage cell line as an in vitro model,Detected levels of cellular oxida-tive stress(ROS),apoptosis and expressions of PI3K/Akt signaling pathway proteins.CCK-8 was used to detect effect of Tongguan Fang drug-containing serum on cellular inflammation.Effects of Tongguan Fang-containing serum on cell inflammation were assessed using CCK-8 assay.Cells were divided into control group,LPS-induced inflammation model group,and Tongguan Fang-containing serum-treated LPS-induced inflammation model groups of different concentrations.qPCR was performed to detect mRNA expression levels of IL-1β,IL-6 and TNF-α in different groups.Immunofluorescence and Western blot were used to evaluate phosphorylation levels of the PI3K/Akt signaling pathway and protein levels of Bcl-2,Bax and caspase-3 of apoptotic.Hoechst 33342/PI staining and flow cytometry were employed to assess the impact of Tongguan Fang-containing serum on cell apoptosis.DCFH-DA probe was used to measure cellular ROS levels affected by Tongguan Fang-containing serum.Results:①Tongguan Fang-containing serum reduced LPS-induced cellular injury in a dose-dependent manner;②Tongguan Fang-containing serum decreased production of pro-inflammatory cytokines IL-6,IL-1β and TNF-α induced by LPS;③Tongguan Fang-containing serum reduced intracellular ROS generation induced by LPS;④Pre-treatment with Tongguan Fang-containing serum activated PI3K/Akt signaling pathway;⑤Tongguan Fang-containing serum promoted cell apoptosis.Conclusion:Treatment with Tongguan Fang-containing serum can reduce cellular injury and inflam-mation,protect cells from LPS-induced cellular injury by activating the PI3K/Akt signaling pathway and promoting cell apoptosis,and further alleviate cellular inflammation levels.

Objective:To investigate the effect of Tongguan Fang drug-containing serum on LPS-induced inflammation of RAW264.7 cells,so as to clarify the cellular mechanism of the Tongguan Fang in treating tubal inflammatory infertility.Methods:Lipo-polysaccharide(LPS)was used to stimulate the RAW264.7 macrophage cell line as an in vitro model,Detected levels of cellular oxida-tive stress(ROS),apoptosis and expressions of PI3K/Akt signaling pathway proteins.CCK-8 was used to detect effect of Tongguan Fang drug-containing serum on cellular inflammation.Effects of Tongguan Fang-containing serum on cell inflammation were assessed using CCK-8 assay.Cells were divided into control group,LPS-induced inflammation model group,and Tongguan Fang-containing serum-treated LPS-induced inflammation model groups of different concentrations.qPCR was performed to detect mRNA expression levels of IL-1β,IL-6 and TNF-α in different groups.Immunofluorescence and Western blot were used to evaluate phosphorylation levels of the PI3K/Akt signaling pathway and protein levels of Bcl-2,Bax and caspase-3 of apoptotic.Hoechst 33342/PI staining and flow cytometry were employed to assess the impact of Tongguan Fang-containing serum on cell apoptosis.DCFH-DA probe was used to measure cellular ROS levels affected by Tongguan Fang-containing serum.Results:①Tongguan Fang-containing serum reduced LPS-induced cellular injury in a dose-dependent manner;②Tongguan Fang-containing serum decreased production of pro-inflammatory cytokines IL-6,IL-1β and TNF-α induced by LPS;③Tongguan Fang-containing serum reduced intracellular ROS generation induced by LPS;④Pre-treatment with Tongguan Fang-containing serum activated PI3K/Akt signaling pathway;⑤Tongguan Fang-containing serum promoted cell apoptosis.Conclusion:Treatment with Tongguan Fang-containing serum can reduce cellular injury and inflam-mation,protect cells from LPS-induced cellular injury by activating the PI3K/Akt signaling pathway and promoting cell apoptosis,and further alleviate cellular inflammation levels.

【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.

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

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.