Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging. However, investigations into the microstructural pathology of brain white matter (WM) associated with these deficits remain limited. This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination, utilizing Neurite Orientation Dispersion and Density Imaging (NODDI), and to explore their correlations with cognitive functions and cognition-related plasma biomarkers. The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls, characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index. Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation, superior longitudinal fasciculus, cingulum, and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers. These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction, potentially serving as early markers for cognitive decline.
Humans ; White Matter/pathology* ; Male ; Female ; Cognitive Dysfunction/physiopathology* ; Middle Aged ; Aged ; Color Perception/physiology* ; Brain/pathology* ; Neuropsychological Tests ; Diffusion Tensor Imaging

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

Objective To investigate the changes in the tumor microenvironment of pancreatic cancer(PDAC)complicated with diabetes mellitus(DM)in a mouse model of hyperglycemia and orthotopic pancreatic cancer by analyzing transcriptome and single-cell transcriptome data in order to identify potential therapeutic targets.Method By integrating single-cell transcriptome and bulk transcriptome data,bioinformatics analysis was conducted to compare the characteristics of tumor cells and tumor immune microenvironment between PDAC patients with DM(DM group)and those without DM(non-DM group).Twenty male C57BL/6 mice(6 weeks old,weighing 18～20 g)were randomly divided into a hyperglycemic group[STZ group,continuous intraperitoneal injection of 50 mg/kg streptozocin(STZ)(final concentration of 1％)dissolved in citrate buffer],and a control group(Control group,an equivalent volume of citrate buffer without STZ at the same time points),with 10 mice in each group.Tail-tip blood glucose level was measured to monitor glycemic status.After orthotopic inoculation of pancreatic cancer cells in both Control and STZ groups,tumor-infiltrating immune cells were harvested.Flow cytometry was employed to determine the effects of hyperglycemia on:total CD8+T cell and Treg cell populations;CD8+T cell subsets expressing Ki67,TNF-α,granzyme B(GZMB)and IFN-γ;surface expression of PD-1,lymphocyte activation gene-3(LAG-3)and T cell immunoglobulin and mucin domain-3(Tim-3)on CD8+T cells;programmed death-ligand 1(PD-L1)expression on tumor cells;and tumor-associated macrophage surface expression of major histocompatibility complex classⅠ(MHC-Ⅰ)and cluster of differentiation 206(CD206).Results Bioinformatics analysis revealed that,compared to the non-DM group,the genes significantly up-regulated in the DM group were associated with poor prognosis(P＜0.001).The proportion of type 2 ductal cells was increased in the DM group,exhibiting higher levels of copy number variation(P＜0.001).In the tumor immune microenvironment of the DM group,there was an increase in the proportion of Treg cells(P＜0.05)and an elevated exhaustion score for CD8+T cells(P＜0.001),accompanied by down-regulated expression of effector molecules,up-regulated expression of inhibitory checkpoints,and a significant increase in the M2 score of M2-like macrophages(P＜0.001).Animal experiments and flow cytometry found that,compared to the Control group,the STZ group had a shorter survival time(P＜0.001),with decreased proportions of total CD8+T cells(P＜0.01)and CD8+T cells expressing Ki67,TNF-α,GZMB and IFN-γ(P＜0.01),increased proportion of Treg cells(P＜0.001),up-regulated expression of PD-1,LAG-3 and Tim-3 on the surface of CD8+T cells(P＜0.001),and up-regulation of PD-L1 on tumor cell surface(P＜0.001)and enhanced expression of CD206 on the surface of tumor-associated macrophages,while down-regulated expression of MHC-Ⅰ(P＜0.001).Conclusion High glucose promotes the formation of an immunosuppressive microenvironment in PDAC,and targeting type 2 ductal cells and immunosuppressive cells in the tumor microenvironment,combined with dual immune checkpoint antibody therapy,may improve patient prognosis.

Objective:Rejection remains the most important factor limiting the survival of transplanted kidneys.Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection,its limitations prevent it from being used as a routine monitoring method.Recently,peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system,however,its application value and strategy in the field of kidney transplantation need further exploration.Additionally,the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases.This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection(TCMR)and antibody-mediated rejection(ABMR),as well as their diagnostic value,in conjunction with routine blood tests. Methods:A total of 154 kidney transplant recipients,who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December,2021,were selected as the study subjects.They were assigned into a stable group,a TCMR group,and an ABMR group,based on the occurrence and type of rejection.The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups.The transplant kidney function,routine blood tests,and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group. Results:The stable,TCMR group,and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys(all P>0.05).However,the post-transplant duration was significantly longer in the ABMR group compared with the stable group(P<0.001)and the TCMR group(P<0.05).Regarding kidney function,serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group(both P<0.01),with the TCMR group also showing higher levels than the stable group(P<0.01).Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group(P<0.01),with no statistically significant difference between TCMR and ABMR groups(P>0.05).The estimated glomerular filtration rate(eGFR)was lower in both TCMR and ABMR groups compared with the stable group(both P<0.01).In routine blood tests,the ABMR group had lower hemoglobin,red blood cell count,and platelet count than the stable group(all P<0.05).The TCMR group had higher neutrophil percentage(P<0.05)and count(P<0.05)than the stable group,and the ABMR group had a higher neutrophil percentage than the stable group(P<0.05).The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups(all P<0.05).Both TCMR and ABMR groups had lower basophil percentage and count,as well as lower lymphocyte percentage and count,compared with the stable group(all P<0.05).There were no significant differences in monocyte percentage and count among the 3 groups(all P>0.05).In lymphocyte subpopulations,the TCMR and ABMR groups had lower counts of CD45+cells and T cells compared with the stable group(all P<0.05).The TCMR group also had lower counts of CD4+T cells,NK cells,and B cells than the stable group(all P<0.05).There were no significant differences in the T cell percentage,CD4+T cell percentage,CD8+T cell percentage and their counts,CD4+/CD8+T cell ratio,NK cell percentage,and B cell percentage among the stable,TCMR,and ABMR groups(all P>0.05). Conclusion:The occurrence of rejection leads to impaired transplant kidney function,accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients.The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.

Objective To explore the expression of serum fatty acid-binding protein 4(FABP4)and fibroblast growth factor 19(FGF19)in patients with β-thalassemia and their relationship with clinical prognosis.Methods A total of 112 cases ofβ-thalassemia patients diagnosed and treated in Qianjiang Hospital Affiliated to Chongqing University from January 2018 to August 2020 were selected as the case group,and 60 healthy individuals who underwent physical examinations during the same period were taken as the control group.Enzyme-linked immunosorbent assay was used to detect levels of serum FABP4 and FGF19 expression.Multivariate logistic regression analysis was used to analyze factors affecting the prognosis of patients with β-thalassemia.Receiver operating characteristic curve was used to analyze the prognostic value of FABP4 and FGF19 in patients with β-thalassemia.Results The serum FABP4 level(67.13±11.35 μg/L)in the case group was higher than that in the control group(22.01±4.16μg/L),while the serum FGF19 level(104.24±21.46 ng/L)was lower than that in the control group(218.01±36.79 ng/L),with significant differences(t=29.708,25.620,all P＜0.05).The serum FABP4 levels(54.20±12.63 μ g/L,66.83±10.5 μ g/L,79.72±11.05 μ g/L)in the mild group,intermediate group,and severe group were increased sequentially,while FGF19 levels(122.53±22.36 ng/L,103.16±20.37 ng/L,86.53±18.14 ng/L)were decreased sequentially,and the differences were significant(F=39.701,24.231,all P＜0.05).Compared to the survival group,serum FGF19 level(62.80±22.09 ng/L vs 110.16±20.69 ng/L),Hb and the proportion of heterozygous genotypes in the death group patients(β CD17/β N,β CD41-42/β N)was lower,while serum FABP4(116.69±12.30 ng/L vs 60.05±10.17 ng/L),ferritin and the proportion of cardiac enlargement were higher,with significant differences(t/x2=4.436～18.981,all P＜0.05).FGF19(OR=0.634,95％CI:0.451～0.891)was an independent protective factor for β-thalassemia patients(P＜0.001),and serum FABP4(OR=1.840,95％CI:1.193～2.838)was an independent risk factor for prognosis(P＜0.001).The area under the curve(95％CI)of serum FABP4 and FGF19 combination in prognosis evaluation for β-thalassemia patients was 0.897(0.853～0.951),which was greater than the single serum indicator detection of 0.842(0.801～0.879)and 0.814(0.762～0.858),with significant differences(Z=4.864,5.270,P=0.002,0.001).Conclusion The serum FABP4 expression is increased,but serum FGF19 expression is decreased in patients with β-thalassemia.The combination of serum FABP4 and FGF19 may have a high predictive value for the prognosis of patients with β-thalassemia.

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor

Objective:To investigate the demand and influencing factors of home care social support services for the elderly with dementia in urban areas, and provide a decision-making basis for improving home care social support services for the elderly with dementia.Methods:This was a cross-sectional study. From March 2021 to March 2022, 386 family caregivers of elderly people with dementia were randomly selected from tertiary hospitals in four central urban areas of Wuhan by stratified sampling method. A questionnaire was used to investigate the current situation and attributes of the demand for home care social support services for the elderly with dementia in urban areas. The importance of the demand for home care social support services for the elderly with dementia in urban areas was calculated by the Better-Worse coefficient method and sensitivity formula method. The optimal scale regression model was used to analyze the influencing factors and influencing forces of independent variables on service demand.Results:The score of social support service demand for home care was (88.6 ± 29.71) points. The Better coefficient of demand for all social support services was greater than the absolute value of the Worse coefficient. One requirement (pressure ulcer prevention and treatment guidance) was a one-dimensional attribute, and the remaining 29 items were charm attributes. The top 6 items in importance ranking were 2 items of informational support (pressure ulcer prevention and treatment guidance; telephone counselling guidance for family caregivers), 1 items of instrumental support (financial assistance for family caregivers) and 3 items of social companionship support(cultural recreation/physical activity activities, door-to-door accompaniment, accompany the elderly to social activities). Optimal scale regression model test: all four models of social support service demand were statistically significant ( F values were 2.75-4.23, all P <0.01). The gender, education level, number of children of the elderly with dementia, age,education level, self rated physical condition of family caregivers, the average monthly income of families, and the relationship between family caregivers and the elderly with dementia were the influencing factors of self-esteem support (all P<0.05). The educational level, marital status, type of dementia of the elderly with dementia, educational level, self rated physical condition of family caregivers, the average monthly income of the family, and the relationship between family caregivers and the elderly with dementia were the influencing factors of informational support (all P <0.05). The educational level and type of dementia of the elderly with dementia, the educational level, self rated physical condition of family caregivers, and the average monthly income of families were the influencing factors of social companionship support (all P <0.05). The type of dementia of the elderly with dementia, the self rated physical condition of family caregivers, the average monthly income of families, and the relationship between family caregivers and elderly relatives were the influencing factors of instrumental support (all P <0.05). Five times for caregiver human resources, 3 times for family economic resources and 3 times for the elderly with dementia, and 1 time for relatives resource factors were the top 3 times of independent variable influence force entered the ranking. Conclusions:The demand for social support services for home care of the elderly with dementia is low, with the characteristics of expectant tendency and centralized demand. The provision of home-based care social support services should give priority to meeting the needs of "pressure ulcer prevention and treatment guidance", and provide financial assistance, counseling and guidance, social companionship and other services as much as possible. Caregiver human resources are the key factors affecting home care social support services, family economic resources and the elderly with dementia are important factors, it is recommended to fully tap the potential of relatives resources and community resources.

Objective:To evaluate the risk factors for prognosis of primary intussusception treated by enema reduction in children.Methods:A retrospective analysis of 519 patients with primary intussusception in Anhui Provincial Children′s Hospital from January 2017 to December 2020 was performed. Among the 519 patients, there were 346 males and 173 females. The median age was 15 months, with a range of 3 to 69 months, some basic information was collected. Patients were divided into bad prognosis group ( n=71) and good prognosis group ( n=448) according to prognosis.Propensity score matching (PSM) was conducted to reduce confounding bias between the groups. Conditional logistic regression were used to analysis the risk factors of primary intussusception treated by enema reduction. Results:There were 71 cases of poor prognosis among 519 primary intussusception patients, incidence was 13.7%.Before PSM, there was significant difference in 6 covariates, including gender, age, duration of symptoms, bloody stool, diarrhoea and fever between two group ( P<0.05). There was no significant difference in abdominal pain and vomit between two group ( P>0.05). With propensity score matching, 69 pairs of patients were sucessfully matched. After PSM, distribution of the above covariates reached equilibrium between two groups ( P>0.05). There were statistically significant differences in enema reduction, mass location, seroperitoneum, lactic acid and overweight/obese between the two groups ( P<0.05). Conditional logistic regression analysis confirmed that enema reduction( OR=3.478, 95% CI: 1.150-10.517, P=0.027), mass location ( OR=6.596, 95% CI: 1.669-26.056, P=0.007), lactic acid( OR=1.012, 95% CI: 1.003-1.021, P=0.010), overweight/obese ( OR=6.085, 95% CI: 1.650-22.436, P=0.007) were independent factors for predicting prognosis of primary intussusception treated by enema reduction. Conclusions:AER, mass located left hemicolon, elevated lactic acid and overweight/obese were independent risk factors for poor prognosis of primary intussusception treated by enema reduction.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.