Acetaminophen (APAP) is the primary cause of drug-induced acute liver failure. Ovarian tumor deubiquitinase 6A (OTUD6A), a recently discovered deubiquitinase of the OTU family, has been primarily studied in tumor contexts. However, its role in APAP-induced liver injury (AILI) remains unclear. Therefore, this study aimed to investigate the involvement of OTUD6A in the pathogenesis of AILI. Our findings demonstrated a substantial upregulation of OTUD6A in both the liver tissue and isolated hepatocytes of mice following APAP stimulation. OTUD6A knockout exacerbated APAP-induced inflammation, hepatocyte necrosis, and liver injury, whereas OTUD6A overexpression alleviated these pathologies. Mechanistically, OTUD6A directly interacted with the enhancer of zeste homolog 2 (EZH2) and selectively removed K48-linked polyubiquitin chains from EZH2, enhancing its stability. This resulted in increased protein levels of EZH2 and H3K27me3, as well as reduced endoplasmic reticulum (ER) stress and cell death in hepatocytes. Collectively, our research uncovers a novel role for OTUD6A in mitigating APAP-induced liver injury by promoting EZH2 stabilization.

Objective: To observe the immediate effect of small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation in improving the correction of braces for adolescent idiopathic scoliosis. Methods: A total of 50 cases of adolescent idiopathic scoliosis were selected and given brace correction first. The whole spine anteroposterior and lateral radiographs were taken, the Cobb angle was measured, and the visual analog scale (VAS) score of pain caused by brace wearing was recorded. After removal of the brace, small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation was performed once. After treatment, the same brace was put on again to take a whole spine anteroposterior radiograph, the Cobb angle was measured, and the VAS score was recorded. The changes in Cobb angle and VAS score after manipulation were compared, and the immediate efficacy was evaluated. Results: After the manipulation, the Cobb angle was significantly smaller than that before treatment (P<0.01) and the VAS score was significantly lower than that before treatment (P<0.01). Conclusion: Small-angle Tui-Pushing and An-Pressing anti-rotation bone-setting manipulation can improve the immediate efficacy of brace in treating adolescent idiopathic scoliosis and relieve the pain caused by brace wearing at the same time.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

BACKGROUND: Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. METHODS: All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. RESULTS: A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%). CONCLUSIONS Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.
Acute Disease ; Aneurysm, Dissecting/diagnosis* ; China ; Hematoma ; Humans ; Male ; Middle Aged ; Registries ; Retrospective Studies ; Time Factors ; Treatment Outcome

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l

Objective:To observe the activation of microglia and the expression of inflammatory factors in hippocampus of mice with depression-like behavior after mother-infant separation （MS） combined with lipopolysaccharide （LPS） stress， and to explore the possible anti-depression mechanisms of Wenyang （WY）， Jieyu （JY）， and Wenyang Jieyu （WYJY） prescriptions from the perspective of warming Yang and relieving depression. Method:Seventy offspring mice were randomly divided into a normal group （n=10）， a LPS stress group （n=10）， and a modeling group （n=50）. After undergoing 8 h·d^-1 mother-infant separation during postnatal day 5 （PD₅）–PD₁₄， mice in the modeling group were further divided into the MS + LPS group， WY group， JY group， WYJY group， and fluoxetine （FLU） group， with 10 in each group. The birth date of the offspring mice was recorded as PD₀. The mice in the normal， LPS， and MS + LPS groups were fed a normal diet during PD₂₁–PD₉₀， while those in the other groups were treated with the mixtures of corresponding drugs and feed， followed by seven-day intraperitoneal injection of LPS since PD₉₁ for inducing depression. The depression-like behavior of mice in each group was detected in the open-field， O-maze， and social interaction tests. The protein expression of microglia-specific ionized calcium-binding adaptor molecule 1 （Iba-1） in the hippocampus was assayed by immunohistochemistry， and the mRNA expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， Iba-1， and glucocorticoid receptor （GR） by real-time fluorescence quantitative PCR （Real-time PCR）. Result:Compared with the normal group， the LPS group exhibited significantly reduced residence time at the central area within 5 min （P<0.01） and shortened total exercise distance （P<0.01）. In the MS + LPS group， the open-arm activity time and the total activity distance decreased significantly （P<0.01， P<0.05）， whereas the training， discrimination and exploration time increased significantly （P<0.01）. The expression of Iba-1 in hippocampal CA1 region of mice in the LPS and MS + LPS groups was remarkably elevated （P<0.01）. Compared with the LPS group， the MS + LPS group displayed significantly prolonged distance of 5-min exercise （P<0.05）， increased training， discrimination and exploration time （P<0.05， P<0.01）， and up-regulated Iba-1 expression in hippocampal CA1 area （P<0.01）. As revealed by comparison with the MS + LPS group， both the total 5-min exercise distance （P<0.01） and the training and discrimination time （P<0.01， P<0.05） of mice in each administration group was significantly shortened. The discrimination and exploration time of mice in the JY， WYJY， and FLU groups was significantly reduced （P<0.01）， and the expression of Iba-1 in hippocampal CA1 region of mice in each administration group was significantly down-regulated （P<0.01）. Conclusion:The warming Yang and relieving depression method helps to inhibit the occurrence and development of depression due to its efficacy in activating microglia in hippocampus of depression mice and lowering the expression of IL-1β， IL-6， and TNF-α.

Objective:To observe the activation of microglia in hippocampus of depressed and anxious mice induced by maternal separation with acute restraint stress and the expression of interleukin-1β（IL-1β），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α）， investigating the mechanism of Wenyang Jieyu prescription in treating anxiety and depression. Method:Eighty four male C57BL offspring were randomly divided into control group， acute restraint stress group and model group on postnatal day 0（PD0）. Maternal separation combined with acute restraint stress was used to prepare anxious and depressed model mice， dividing the model mice into model group， Wenyang， Jieyu， Wenyang Jieyu and fluoxetine group according to random number table method. During the period of PD21-PD90， the control， acute restraint stress and model mice were fed with normal diet， with the other groups fed with corresponding medicine mixed diet. The Wenyang， Jieyu and Wenyang Jieyu groups were given 5.85， 12.03 and 16.71 g·kg^-1·d^-1 respectively. The fluoxetine group was given 2.60 mg·kg^-1·d^-1. Open field， zero maze test and social interaction tests were used to evaluate the anxiety and depression of model mice. The expression of Iba-1 in hippocampal microglia was detected by immunohistochemistry（IHC）. The mRNA expression of IL-1β， IL-6， TNF-α， Iba-1 and glucocorticoid receptor（GR）were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the control group， total movement distance and time spent in central zone in 5 min of the model mice significantly decreased（P<0.01）， time spent in opened arm and total movement distance decreased significantly（P<0.05，P<0.01）， investigation time during testing and training increased significantly（P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly increased（P<0.01）， the expression levels of GR mRNA significantly decreased（P<0.01）. The result of IHC staining showed that microglia were over activated. Compared with the model group， total movement distance and time spent in central zone in 5 min of mice in the Wenyang Jieyu and fluoxetine group significantly increased（P<0.05，P<0.01）.Time spent in opened arm significantly increased（P<0.01）. Investigation time during testing and training significantly decreased（P<0.05，P<0.01）. The expression of Iba-1 protein and mRNA，IL-1β，IL-6，TNF-α mRNA significantly decreased（P<0.05，P<0.01）. The expression of GR mRNA increased significantly（P<0.05，P<0.01）. IHC staining showed the microglia recovered. Time spent in opened arm of mice in the Wenyang group and Jieyu group significantly increased （P<0.01）， time spent investigating during testing decreased significantly （P<0.05）， the expression levels of Iba-1 protein and mRNA，IL-6 mRNA significantly decreased （P<0.05，P<0.01）. The expression of GR mRNA of mice in the Wenyang group significantly increased （P<0.05）， the expression of TNF-α mRNA significantly decreased （P<0.05）. Total movement distance of mice in the Jieyu group increased significantly （P<0.01）， time spent investigating during training decreased significantly （P<0.05），the expression level of IL-1β mRNA significantly decreased （P<0.05）. IHC staining showed that microglia recovered partly in both groups. Conclusion:The comprehensive curative effect and pharmacological action of Wenyang Jieyu prescription were better than Wenyang prescription and Jieyu prescription. Wenyang Jieyu prescription can treat anxiety and depression in maternal separation and acute restraint stress mice， its possible mechanism may be related to the decreased activation of microglia， down-regulation of IL-1β，IL-6，TNF-α expression and up-regulation of GR expression.

Objective:To investigate the clinical effect of Chaihu Shugansan combined with abdominal acupuncture on depression caused by chronic pain，and to explore its mechanism. Method:A total of 97 patients with depression caused by chronic pain were randomly divided into control group （49 cases） and observation group （48 cases）. Patients in both groups received routine western medicine treatment，including necessary psychological intervention and taking paroxetine. Control groupobservation groupcontrol group Patients in control group were treated with Xiaoyaowan，and patients in observation group were treated with Chaihu Shugansan combined with abdominal acupuncture. Both groups were treated for 6 weeks. The levels of serum neurotransmitters，cytokines and Hamilton depression rating scale（HAMD） before and after treatment were compared between two groups. Result:There was no significant difference in HAMD scores of the two groups before treatment and the HAMD scores of two groups after treatment were significantly lower than those before treatment （P<0.05），and the HAMD scores in observation group were significantly lower than those in the control group （P<0.05）. There was no significant difference in the levels of serum 5-hydroxytryptamine （5-HT），norepinephrine （NE），and brain-derived neurotrophic factor （BDNF） between two groups before treatment. After treatment，the levels of serum 5-HT，NE，and BDNF in two groups were significantly higher than those before treatment （P<0.05），and the levels in observation group were significantly higher than those in control group （P<0.05）. There was no significant difference in the levels of serum interleukin-6 （IL-6），interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） before treatment. After treatment，the levels of serum IL-6，IL-1β and TNF-α were significantly lower than those before treatment （P<0.05），and the levels in observation group were significantly lower than those in control group （P<0.05）. Conclusion:On the basis of psychological intervention and paroxetine administration，the combination of Chaihu Shugansan and abdominal acupuncture exerts their respective advantages. It treats both symptoms and root causes of depression，relieves the degree of depression，reduces the classification of depression，and regulates the levels of neurotransmitter and cellular inflammatory factors，and inhibits inflammatory response. The clinical effect is significant.

Background: Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy. Methods: Forty Hartley guinea pigs were divided into four groups according to the NiSO₄ sensitizing concentration and the NiSO₄ challenged concentration: the 5% NiSO₄-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO₄-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-μ-XRF) and micro X-ray absorption near-edge spectroscopy (μ-XANES). Results: In each section, the nickel element concentration in both the 5% NiSO₄-group and 10% NiSO₄-group was significantly higher than that in the negative control group. In the upper 300-μm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (<200 μm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-μ-XRF. According to the XANES data for the 10% NiSO₄ metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni²⁺ aqueous ionic state but in the nickel-binding protein. Conclusions This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni²⁺ aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.

BACKGROUNDRepetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ.

METHODSOne hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group.

RESULTSCompared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05).

CONCLUSIONSBased on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.