Background Manganese is an essential trace element for the human body and maintains normal development of many organs including the brain. However, long-term exposure to a high manganese environment or excessive manganese intake will lead to manganese poisoning and result in neurological diseases, and currently no effective treatment plan is available. Objective To develop an animal model for subchronic manganese exposure and assess the impact of Dendrobium nobile Lindl. alkaloids (DNLA) on manganese associated behavioral and hippocampal effects in rats. Methods Fifty male SPF SD rats were randomly allocated into a control group (0.9% normal saline by intraperitoneal injection), two experimental groups [7.5 mg·kg⁻¹ (low) or 15 mg·kg⁻¹ (high) of MnCl₂·4H₂O by intraperitoneal injection], and two DNLA antagonistic groups [15 mg·kg⁻¹ MnCl₂·4H₂O by intraperitoneal injection then either 20 mg·kg⁻¹ (low) or 40 mg·kg⁻¹ (high) DNLA by oral administration]. All groups of rats were adminaistered 5 d per wek, once a day, for consecutive 13 weeks. Following modeling, neurobehavioral assessments were conducted using open field, Morris water maze, and Y maze. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to measure manganese levels in the blood and brain tissues of the rats, and hematoxylin-eosin (HE) staining was employed to examine neuronal morphological changes in the hippocampal tissues of the rats. Results The neurobehavioral tests revealed that the manganese-exposed rats exhibited decreased total movement distance, prolonged central zone dwelling time, and reduced motor activity in the open field test, indicating tendencies toward depression and anxiety (P<0.05). In the Y-maze test, the mean exploration distance in the novel arm, the number of entries into the novel arm, and the time spent in the novel arm of the managanses-exposed rats were all reduced, while the latency period increased, suggesting impaired spatial exploration and learning-memory functions (P<0.05). In the Morris water maze navigation test, the escape latency was significantly longer in the manganese-exposed rats compared to the control group, and the number of platform crossings decreased in the spatial probe test, indicating a significant decline in spatial learning and memory (P<0.05). The ICP-MS analysis showed elevated manganese concentrations in the blood and hippocampus of the exposed rats (P<0.05), and the histopathological observation revealed hippocampal damage. Following the DNLA intervention, the manganese-exposed rats showed increased total movement distance and reduced central zone dwelling time in the open field test (P<0.05). In the Y-maze test, the mean exploration distance in the novel arm, the number of entries into the novel arm, and the time spent in the novel arm increased, while the latency period decreased, suggesting alleviation of anxiety and improved exploratory behavior (P<0.05). In the Morris water maze test, the escape latency gradually shortened, and both the number of platform crossings and the percentage of time spent in the target quadrant increased, indicating improved spatial learning and memory (P<0.05). Additionally, the manganese levels in the blood and hippocampus decreased (P<0.05), and the hippocampal pathological changes were partially restored. Conclusion DNLA demonstrates the ability to counteract multiple neurotoxic effects following the elevation of manganese levels in the blood and hippocampal tissues of rats induced by subchronic manganese exposure. Specifically, DNLA is shown to ameliorate the behavioral alterations observed in rats after manganese exposure, and mitigate the hippocampal damage in manganese-exposed rats.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

This study aims to explore whether Guzheng playing training has a positive impact on the brain functional state of children with Autism Spectrum Disorder (ASD) based on power spectral and sample entropy analyses. Eight ASD participants were selected to undergo four months of Guzheng playing training, with one month as a training cycle. Electroencephalogram (EEG) signals and behavioral data were collected for comparative analysis. The results showed that after Guzheng playing training, the relative power of the alpha band in the occipital lobe of ASD children increased, and the relative power of the theta band in the parietal lobe decreased. The differences compared with typically developing (TD) children were narrowed. Moreover, some channels exhibited a gradual increase or decrease in power with the extended training period. Meanwhile, the sample entropy parameter also showed a similar upward trend, which was consistent with the behavioral data representation. The study shows that Guzheng training can enhance the brain function of ASD patients, with better effects from longer training. Guzheng playing training could be used as a daily intervention for autism.
Humans ; Electroencephalography ; Entropy ; Music Therapy ; Child ; Brain/physiopathology* ; Autism Spectrum Disorder/therapy* ; Male ; Female ; Autistic Disorder/therapy*

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective To explore the mortality rate and changes in splenic cell cycle and apoptosis in rats with ab-dominal infection.Methods An animal model of sepsis was induced by cecal ligation and puncture(CLP)in rats.At serial time points 0 h,6 h,12 h,24 h,48 h,and 72 h after CLP,the animal death rate was calculated.The percentage of cell cycle G1,S,G2/M phase and apoptosis of isolated spleen cells were analyzed using flow cytome-ter.The expression of p27 of spleen tissue was determined by Western blot analysis.Results In the rat model of CLP-induced systemic inflammatory response,the mortality of animals gradually increased at 0 h,6 h,12 h,24 h,48 h and 72 h after CLP surgery,reaching a maximum of 88.81%.The abdominal infection in the animals gradual-ly worsened at 0 h,6 h,12 h,and 24 h after CLP surgery,but localized and gradually alleviated after 48 h and 72 h.Within 48 h after CLP surgery,there was a blockage in the G1 phase of the spleen cell cycle,an increase in the percentage of apoptotic cells,and an elevation in p27 expression.After 48 h,the G1 phase blockage gradually recovered,the number of apoptotic cell decreased,and p27 expression declined.Additionally,with-in 48 h after CLP surgery,there was a decrease in the percentage of cells in the S and G2/M phases of the spleen cell cycle,but the percentage of cells in these phases gradually increased after 48 h.Conclusions Cell cycle arrest and apoptosis of the spleen cells are potentially contributed to the change of animal mortality after abdominal infection.

Objective:To evaluate the effect of vagus nerve stimulation on the homologous phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/Parkin signaling pathway on myocardial injury induced by hepatic ischemia-reperfusion (I/R) in rats.Methods:Twenty-seven clean-grade healthy male Sprague-Dawley rats, aged 10-12 weeks, weighing 280-320 g, were divided into 3 groups ( n=9 each) using a random number table method: sham operation group (Sham group), hepatic I/R group (HI/R group) and vagus nerve stimulation group (VNS group). The liver I/R injury model was made by clamping the liver pedicle for 1 h followed by 6-h reperfusion. In VNS group, the left cervical vagus nerve was stimulated by a voltage with a frequency of 20 Hz and a wave width of 0.1 ms immediately after liver ischemia, lasting for 1 h. The stimulation voltage was adjusted with the rat heart rate, and the heart rate decreased by more than 10% of the basic value was considered as a successful stimulation. The rats were anesthetized at the end of reperfusion, and carotid blood samples were collected for determination of the serum cardiac troponin I (cTnI) concentration by enzyme-linked immunosorbent assay. Then rats were sacrificed, and left ventricular myocardial tissues were taken for determination of the apoptosis in cardiomyocytes (by TUNEL) and expression of PINK1, Parkin, p62, Bax and Bcl-2 (by Western blot). The apoptosis rate was calculated. Results:Compared with Sham group, the concentrations of serum cTnI and apoptotic rate of cardiomyocytes were significantly increased, the expression of PINK1, Parkin and Bcl-2 in myocardial tissues was down-regulated, and the expression of p62 and Bax was up-regulated in HI/R group and VNS group ( P<0.05). Compared with HI/R group, the concentrations of serum cTnI and apoptotic rate of cardiomyocytes were significantly decreased, the expression of PINK1, Parkin and Bcl-2 in myocardial tissues was up-regulated, and the expression of p62 and Bax was down-regulated in VNS group ( P<0.05). Conclusions:The mechanism by which vagus nerve stimulation alleviates myocardial injury induced by hepatic I/R is related to activation of the PINK1/Parkin signaling pathway in rats.

Objective:To investigate the association between metabolically healthy overweight/obesity(MHO) and risk of new-onset diabetes among Chinese adults.Methods:This study was a secondary analysis of a retrospective cohort study recruiting 117 056 Chinese adults who received a health check at the Rich Healthcare Group from 2010 to 2016.Participants were classified into metabolically healthy non-obesity(MHNO), MHO, metabolically unhealthy non-obesity(MUNO), and metabolically unhealthy overweight/obesity(MUO) group according to body mass index and metabolic status at baseline. Kaplan-Meier method(log-rank test) was used to estimate the cumulative incidence of diabetes in each group. The Cox proportional hazards model was employed to estimate the hazard ratios( HR and 95% CI) for diabetes incidence across different obesity metabolic phenotype groups, followed by subgroup analysis. Results:A total of 117 056 Chinese adults were enrolled and the prevalence of MHO was 24.3%. During the follow-up time of (3.1±1.0) years, 2 685 new-onset diabetes adults occurred, resulting in a cumulative incidence rate of 2.3%. The cumulative incidences of MHNO, MHO, MUNO and MUO groups were 0.5%, 1.6%, 4.8%, and 7.9%, respectively, and there was a statistical difference ( χ2=1 224.164, P<0.001). Cox proportional hazards model showed that after adjusting for sex, age, fasting plasma glucose, smoking, alcohol drinking, and diabetes family history, the risk of new-onset diabetes in MHO group was 2.19 folds of MHNO group(95% CI 1.89-2.55). Additionally, the HR for diabetes in MUNO and MUO groups were 2.25(95% CI 1.93-2.64)and 3.00(95% CI 2.61-3.45). Conclusion:The MHO phenotype was significantly associated with an increased risk of new-onset diabetes in Chinese adults.

Reactive arthritis(ReA) is a kind of sterile, non-purulent arthritis that occurs after microbial infections far from the joints.The disease has a broad spectrum, and it can be classified into three categories based on clinical characteristics: human leukocyte antigen B27(HLA-B27)-associated ReA, acute rheumatic fever(ARF), and post-streptococcal reactive arthritis(PSRA).In addition to joints, it may also involve the gastrointestinal tract, skin, eyes, and heart.Unlike adults, the pathogenesis of ReA in children is more complex.HLA-B27-associated ReA is more common after gastrointestinal and respiratory infections, with less involvement of the central axis and sacroiliac joints and more involvement of the hip and peripheral joints and attachment point inflammation.ARF is most common in children aged 5 to 15 years, characterized by migratory and multiple arthritis.The duration of onset of PSRA in children is shorter than that in adults.This article reviews the epidemiology, clinical manifestations, diagnosis and treatment of ReA in children to improve clinicians′ understanding of ReA in children.