ObjectiveTo observe the effect of Liuwei Dihuangwan on behavioral impairments in the rat model of autism spectrum disorder （ASD） and explore the mechanism of action. MethodsTwelve SD pregnant rats were intraperitoneally injected with valproic acid （VPA） （10 rats） or normal saline （2 rats）， and male offspring were selected to establish the model of ASD and the control rats. Rats were randomly assigned into model， low-dose （0.75 g·kg^-1） and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan， vitamin D （positive drug， 3.7×10^-5 g·kg^-1）， and blank groups. Each group was administrated with the corresponding concentration of drugs or the same volume of normal saline by gavage for 2 weeks. After the intervention， the three-chamber social test was conducted to evaluate social interaction and social preference. The open field test was carried out to observe spontaneous behavior and anxiety state. Hematoxylin-eosin staining （HE） was used to observe the pathological changes of the prefrontal tissue. Transmission electron microscopy was employed to observe the ultrastructure of mitochondria in prefrontal neurons. Immunofluorescence was used to detect the expression of ionized calcium-binding adapter molecule-1 （Iba-1） in the prefrontal tissue. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）. Western blot was employed to assess the expression differences of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated Unc-51-like autophagy-activating kinase 1 （p-ULK1）， Unc-51-like autophagy-activating kinase 1 （ULK1）， and FUN14 domain-containing protein 1 （FUNDC1）. ResultsCompared with the blank group， the model group spent less time sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.01） and showed reductions in the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.01）. In addition， the model group showed extensive apoptosis of neurons， with shrunken nuclei and red-stained cytoplasm， and extensive necrosis of neurons in the prefrontal tissue， mitochondrial swelling， decreased matrix density， disrupted cristae， and autophagic lysosomes in neurons， increases in the rate of Iba-1 positive cells in the prefrontal area （P<0.01） and the levels of TNF-α and IL-6 （P<0.01）， and down-regulation in the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. Compared with the model group， low-dose and high-dose Liuwei Dihuangwan and the vitamin D prolonged the time spent sniffing stranger 1 and stranger 2 in the three-chamber social test （P<0.05， P<0.01）， increased the total distance traveled， average speed， distance traveled in the central area， and time spent in the central area in the open field test （P<0.05， P<0.01）， restored the morphology of neurons in the prefrontal tissue， decreased the number of apoptotic cells， alleviated the swelling of mitochondria in neurons， increased the matrix density， mitigated the fragmentation and disorder of cristae， and increased the number of autophagosomes. Moreover， the drugs decreased the rate of Iba-1 positive cells in the prefrontal area （P<0.01）， lowered the levels of TNF-α and IL-6 （P<0.01）， and up-regulated the expression of p-AMPK/AMPK， p-ULK1/ULK1， and FUNDC1 （P<0.01）. ConclusionLiuwei Dihuangwan ameliorate autism-like behaviors and reduce neuronal apoptosis and neuroinflammatory damage in the rat model of ASD by promoting mitophagy mediated by the AMPK/ULK1/FUNDC1 pathway.

Objective: To explore the associations between caregivers nutrition literacy and pediatric nonalcoholic fatty liver disease (NAFLD), so as to provide scientific evidence for the key contents of family intervention measures. Methods: In September 2022, a study involving 1 609 thirdgrade students and their caregivers from six schools in Yinzhou, Haishu, and Zhenhai Districts of Ningbo City, Zhejiang Province, was conducted. Venous blood samples were collected to measure lipid profiles and investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) among the children. Family Food Environment Questionnaire was used to assess the nutrition literacy levels of the caregivers. Generalized linear regression analysis was employed to explore the correlation between caregivers nutrition literacy levels and the prevalence of NAFLD in children. Results: Among the surveyed students, 191 were in the NAFLD group, whereas 1 418 were in the nonNAFLD group. The median nutrition literacy score of caregivers in the NAFLD group and nonNAFLD group all were 11.00 (9.00,12.00), which was not significantly different (Z=-0.40, P=0.71). The generalized linear regression results revealed that the level of nutrition literacy of caregivers had no significant effect on childrens Triglyceride-glucose (TyG) index and Triglyceride-glucose-Waisttoheight ratio (TyG-WHtR) [β(95%CI) were 0.001(-0.005-0.006) and 0.000(-0.014-0.014), P>0.05]. Conclusions The nutrition literacy level of caregivers has no significant correlation with the direct incidence of NAFLD in children. As for family intervention measures, it is necessary not only to improve the nutrition literacy level of caregivers but also to effectively apply nutritional knowledge in practice to optimize health management.

Objective: To evaluates the association between maternal overweight/obesity during pregnancy and offspring risk of metabolic dysfunction associated steatotic liver disease (MASLD), providing theoretical evidence for early life MASLD prevention. Methods: An online search was conducted across ten databases (CNKI, Wanfang, SinoMed, PubMed, Embase, Web of Science, Cochrane Library, PROSPERO, PQDT Global, ScienceDirect) for research literature on the association between maternal overweight/obesity during pregnancy and the development of MASLD in offspring, with the search period spanning from January 2014 to December 2024. Two researchers independently screened literature, extracted data, and assessed study quality. Statistical analysis was performed using R 4.3.3. Results: Ten studies involving 10 229 participants were included, comprising 4 cohort studies and 6 case control studies. Cohort studies showed that maternal overweight and obesity significantly increased offspring MASLD risk ( RR=1.59, 95%CI=1.06-2.39, P <0.05), with moderate heterogeneity ( I 2=56.9%, P =0.07). Case control studies indicated a positive association between maternal overweight/obesity during pregnancy and offspring risk of MASLD( OR=2.00, 95%CI=1.68-2.39, P < 0.05), with low heterogeneity ( I 2=48.8%, P =0.08). Conclusions Maternal overweight/obesity during pregnancy positively correlates with offspring MASLD risk. Gestational weight management may reduce the risk.

Thymocyte selection-associated high mobility group box (TOX), a member of the high mobility group protein super-family, plays an important role in T cell development, functional maintenance, and exhaustion. It has been recently found that TOX exerts critical immunoregulatory functions during pathogen infections, and TOX expression is strongly associated with the intensity and tolerance of host immune responses. This review systematically summarizes the structural and functional features of TOX and focuses on its expression dynamics, mechanisms of action, and immunomodulatory effects during viral, bacterial, and parasitic infections, which provides a theoretical support to better understanding of the role of TOX in infectious diseases and provides new insights into development of potential immunotherapeutic strategies targeting TOX.

Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

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Objective:To develop a health behavior guidance program for stroke rehabilitation patients based on the adaptive leadership framework (ALF) .Methods:Relevant stroke health behavior guidelines were systematically retrieved, screened, included, and recommendations extracted from domestic and international websites. The initial draft of the health behavior guidance program for stroke rehabilitation patients was developed in light of the ALF. From January to March 2022, the draft was refined through two rounds of Delphi expert consultation, resulting in the finalized health behavior guidance program.Results:A total of 10 guidelines were included, and 73 guideline recommendations were extracted. These recommendations were categorized into six dimensions and 25 specific items. In both rounds of expert consultation, 15 questionnaires were distributed and all were returned, yielding an effective recovery rate of 100.00%, with an expert authority coefficient greater than 0.8. Based on expert feedback and group discussions, the final program included eight dimensions and 31 items, adding sleep management and regular health consultations to the original six dimensions.Conclusions:The health behavior guidance program for stroke rehabilitation patients, based on the ALF, introduces a new perspective on nursing by reasonably dividing adaptive and technical problems. This approach aligns with clinical practice in China, providing scientific and practical value for promoting health behaviors and offering a new perspective for health education in stroke patients.

Objective To explored the correlation between diabetic kidney disease(DKD)and MRI of cerebral small vessel disease(CSVD).Methods 476 type 2 diabetes mellitus(T2DM)patients who were hospitalized in Chengdu University of Traditional Chinese Medicine Affiliated Hospital from January to August 2022 were selected and divided into simple T2DM group(UACR＜30 mg/g,n=330)and DKD group(UACR≥30 mg/g,n=146).General data,biochemical indicators and head MRI images of the two groups were compared.The correlation between DKD and CSVD and the influencing factors of white matter hyperintensities(WMHs)severity were analyzed.Results Age,DM duration,TG,Scr,HbA1c,SUA,cystatin C(Cys C),fibrinogen(Fib)and the incidence of hypertension were higher(P<0.05),while the ALT was lower in DKD group than in T2DM group(P<0.05).Spearman correlation analysis showed tha the presence of DKD was positively correlated with WMHs,lacunar infarction(LI)and brain atrophy(P<0.05).eGFR was negatively correlated with WMHs,LI and brain atrophy(P<0.05).Logistic regression analysis showed that age and HbA1c were the influencing factors for the severity of WMHs.Conclusion Patients with DKD have a higher incidence of CSVD,which may be related to worsening renal function.HbA1c may have predictive value for the severity of WMHs.

Objective To comprehend the present condition of sustaining within familial pulmonary rehabilitation for COPD patients,alongside exploring the factors that impact this continuity.Methods A convenience sampling method was used to select 392 COPD patients from outpatient clinics of 2 tertiary-level A hospitals and 1 community health service center in Huaihua in Hunan Province from December 2023 to February 2024 as survey respondents.Patients were surveyed using the general information questionnaire,the COPD Assessment Test,the Modified Medical Research Council Dyspnea Scale,the Exercise Benefits/Barriers Scale,and the Brief 2-Way Social Support Scale.Results We sent out 392 questionnaires and collected 362 valid ones,with an effective response rate of 92.47％.The percentage of COPD patients who never performed home pulmonary rehabilitation was 56.08％,and the maintenance time of health behaviors in home pulmonary rehabilitation was 17.40％for 1-3 months,7.18％for 4-6 months,4.70％for 7-12 months,and 14.64％for more than 1 year.The results of multiple linear regression analysis showed that exercise place,pulmonary rehabilitation health education,exercise habits before having COPD,perceived level of exercise behavior,and two-way social support were influential factors affecting the maintenance of health behaviors in pulmonary rehabilitation in the families of COPD patients,which explained 38.5％of the variability.Conclusion Patients with COPD have a low level of maintenance of health behaviors in home pulmonary rehabilitation,and health education on exercise rehabilitation for COPD patients and caregivers should be strengthened to enhance patients'level of exercise perception and ability to utilize social support.

Objective·To investigate the evolution of sarcoma antigen 1(SAGE1),a member of the cancer-testis antigen(CTA)family,in three representative primate species—Macaca mulatta(Rhesus),Callithrix jacchus(Marmoset),and Microcebus murinus(Mouse Lemur),as well as the conservation of its interaction with INTS3,a subunit of the integrator complex.Methods·The interaction between INTS3 and SAGE1 in these primates and the interaction between INTS3 and human SAGE1 mutants were first validated in HEK293T cells by using co-immunoprecipitation(Co-IP).Truncated proteins were then tagged with His-SUMO and GST,respectively,and expressed in Escherichia coli,followed by a series of purification steps to obtain the target proteins.Surface plasmon resonance(SPR)was used to measure the binding affinity of the target proteins,and size exclusion chromatography with multi-angle light scattering(SEC-MALS)was used to determine the stoichiometry of the complex.Additionally,molecular docking was employed to predict the binding model of the truncated SAGE1 and INTS3.Mutations were performed on human SAGE1 key interface residues to analyze their binding to INTS3 by Co-IP.Results·The interaction between the full-length human-derived INTS3 and the full-length SAGE1 from the three primate species was confirmed by Co-IP.Truncated proteins were purified through multiple steps of tandom chromatography.The dissociation constants of the three pairs of truncated INTS3-SAGE1 were measured via SPR,and the SEC-MALS results demonstrated that the binding ratio of INTS3-SAGE1 was 2∶1.Furthermore,molecular docking predicted a structural model of the truncated INTS3-SAGE1 complex and the binding interface was extensively constituted with hydrophobic contacts assisted by some hydrophilic interactions.The interaction between the mutant SAGE1 and INTS3 full-length protein was significantly weakened.Conclusion·There is a conserved interaction between INTS3 and SAGE1 across Rhesus,Marmoset,and Mouse lemur.