Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes.Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder.However,its therapeutic dosage closely approaches toxic levels.Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L,typically giving rise to gastrointestinal and central nervous system reactions.Cardiac toxicity is rare but serious in cases of lithium poisoning.The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers.This resulted in symptoms such as arrhythmia,shock,impaired consciousness,and coarse tremors.Following symptomatic supportive treatment,including blood dialysis,the patient's physical symptoms gradually improved.It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

This paper reviews the concepts, status, influencing factors and interventions of home self-management of diabetic foot ulcers patients, with a view to providing reference for establishing and improving the home self-management model of diabetic foot ulcers patients suitable for China.

Triangle chronic disease stratified management model, as an effective chronic disease management model, can divide patients into different levels according to the stratified disease assessment criteria, enhance intervention effectiveness, improve management efficiency, and reduce costs by implementing targeted and personalized nursing measures. This article summarizes the overview of the Triangle chronic disease stratified management model, research progress at home and abroad, and the current application status in transitional care for chronic disease patients in order to provide a reference for medical staff to carry out transitional care for chronic disease patients.

Objective:To explore the therapeutic effect of cognitive behavioral therapy (CBT) combined with family intervention on obsessive-compulsive disorder (OCD).Method:A total of 28 patients with OCD who visited the outpatient department of Xiamen Xianyue Hospital from June 2021 to June 2022 were randomly divided into intervention group( n=13)and control group( n=15).Patients in the intervention group and the control group were both received routine drug treatment. On this basis, the patients in intervention group received the treatment of CBT combined with family intervention, while the patients in control group only received CBT treatment.The participants were evaluated at baseline, post-intervention, 1 month and 3 months after the intervention. The Yale-Brown obsessive compulsive scale (Y-BOCS) was used to evaluate the severity of symptoms, and the Sheehan disability scale (SDS) was used to assess their function impairment in patients.The family accommodation scale for OCD interviewer-rated (FAS-IR) was employed to assess family members' family accommodation behavior. Changes in scores on the Y-BOCS scale, SDS scale, and FAS-IR scale scores at each observation time point were used as outcome indicators. The t-test, χ2-test and repeated measure ANOVA were used for statistical analysis by SPSS 25.0 software. Results:(1)The interaction effect of Y-BOCS score between time and group before and after intervention was significant ( F=4.748, P<0.05). The results of the simple effects test showed that the Y-BOCS score of the intervention group at 1 month after the intervention(20.63±5.23)was lower than that of the baseline(27.23±5.12)and post-intervention(24.85±5.94)(both P<0.05). The Y-BOCS score of the intervention group at 3 months after the intervention (16.85±4.62)was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). The Y-BOCS score of the control group at 3 months after the intervention(20.93±7.51) was lower than that of the baseline(25.93±4.68)and post-intervention(25.53±6.57)(both P<0.05).(2)The interaction effect of SDS score between time and group before and after intervention was significant ( F=54.88, P<0.01). The results of the simple effects test showed that the SDS score of the intervention group at post-intervention was lower than that of the baseline( P<0.05).The SDS score at 1 month after the intervention was lower than that of the baseline and post-intervention (both P<0.05). The SDS score of the intervention group at 3 months after the intervention was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). At 3 months after the intervention, the SDS score of the intervention group was lower than that of the control group ( P<0.05).(3)The interaction effect of FAS-IR score between time and group before and after intervention was significant ( F=20.285, P<0.01). The results of the simple effects test showed that post-intervention, the FAS-IR score of the intervention group was lower than that of the baseline( P<0.05).The SDS score at 1 month after the intervention was lower than the baseline and post-intervention (both P<0.05). The FAS-IR score of the intervention group at 3 months after the intervention was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). At 3 months after the intervention, the FAS-IR score of the intervention group was lower than that of the control group ( P<0.05). Conclusion:The CBT combined with family intervention can improve the treatment outcome of OCD, patients' functional impairment, and reduce the occurrence of family accommodation behavior, which providing a basis for family intervention in OCD.

Objective lo investigate the recovery of urinary function and related influencing factors in patients with stress urinary incontinence(SUI)after the tension-free vaginal tape procedure at the mid-urethra.Methods A total of 112 SUI patients who underwent the tension-free vaginal tape procedure at the mid-urethra in Beijing Rehabilitation Hospital Affiliated to Capital Medical University from October 2018 to October 2023 were selected as the research subjects.The postoperative urinary function recovery of all patients was recorded.According to the postoperative urinary function recovery time,patients with a recovery time of≤3 days were included in the rapid recovery group,and those with a recovery time of＞3 days were included in the non-rapid recovery group.Clinical data including age,body mass index,menopausal status,vaginal delivery history,number of deliveries,disease severity,comorbid hypertension,diabetes,history of pelvic organ prolapse,maximum urinary flow rate,postoperative urinary retention,preoperative bladder residual urine volume,maximum bladder volume,hemoglobin(Hb)level,white blood cell(WBC)count,red blood cell(RBC)count,and platelet(PLT)count of patients between the two groups were compared.Factors affecting the recovery of urinary function in SUI patients were analyzed by multivariate logistic regression.Results The recovery time of urinary function in 112 patients with SUI ranged from 1 to 15(4.10±0.78)days.Specifically,64 patients(57.14％)recovered within 3 days,and 48 patients(42.86％)recovered in more than 3 days.The proportions of patients with menopause,history of vaginal delivery,history of pelvic organ prolapse,and postoperative urinary retention in the non-rapid recovery group were significantly higher than those in the rapid recovery group,and the maximum urinary flow rate was significantly lower than that in the rapid recovery group(P＜0.01).There were no significant differences in age,body mass index,number of deliveries,preoperative bladder residual urine volume,maximum bladder volume,Hb level,WBC count,RBC count,PLT count,disease severity,proportion of patients with comorbid hypertension and proportion of patients with diabetes between the two groups(P＞0.05).Multivariate logistic regression analysis showed that menopause,history of vaginal delivery,history of pelvic organ prolapse,postoperative urinary retention and maximum urinary flow rate were influencing factors for the recovery of urinary function in SUI patients after surgery(P＜0.05).Conclusion The recovery of urinary function in SUI patients after a transvaginal tension-free vaginal tape procedure at mid-urethra is not ideal.Menopause,history of vaginal delivery,history of pelvic organ prolapse,postoperative urinary retention and maximum urinary flow rate are the influencing factors for the recovery of urinary function in SUI patients.

Objective:To investigate the effects of continuous blood purification (CBP) on mitochondrial function of peripheral blood mononuclear cells and clinical prognosis of patients with traumatic sepsis.Methods:A prospective cohort study was used to analyze the clinical data of 90 patients with traumatic sepsis admitted to the Intensive Care Unit of Shaoxing People′s Hospital from January 2023 to June 2024. Based on standard operating procedures (SOP), patients were divided into CBP group and non-CBP group according to whether they received CBP treatment. The mitochondrial DNA (mtDNA) copy number, activity of mitochondrial respiratory chain complex V, levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 in the mononuclear cells on ICU admission and at 12, 24 and 48 hours after treatment were compared between the two groups. Acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score on ICU admission and at 48 hours after treatment were detected in the two groups. The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were compared between the two groups.Results:A total of 90 patients with traumatic sepsis were included, comprising 56 males and 34 females, aged 18-82 years [51.3(38.7, 70.6)years], with injury severity score (ISS) of 16-54 points [36.2(17.0, 53.6)points]. There were 52 patients in the CBP group and 38 in the non-CBP group. All the patients were followed up for 7-14 days [10.0(8.0, 12.0)days]. On ICU admission, the mtDNA copy number was 638.5±124.0 in the CBP group and 634.7±122.1 in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the mtDNA copy number in the CBP group was 564.2±105.6, 415.7±83.5 and 303.7±77.0 respectively, significantly lower than 622.9±120.2, 581.5±113.6, 530.7±97.8 in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the mtDNA copy number in both groups continued to decrease compared with that on ICU admission ( P<0.05). On ICU admission, the activity of mitochondrial respiratory chain complex Ⅴ was (74.0±26.0)pg/ml in the CBP group and (72.8±25.3)pg/ml in the non-CBP group ( P>0.05); at 12, 24 and 48 hours after treatment, it was (69.4±24.2)pg/ml, (78.3±26.8)pg/ml and (91.5±33.5)pg/ml respectively in the CBP group, significantly higher than (65.3±23.6)pg/ml, (60.7±19.4)pg/ml and (53.8±16.9)pg/ml in the non-CBP group ( P<0.05 or 0.01); at 12 hours after treatment, it was decreased in both groups compared with that on ICU admission ( P<0.05); at 24 and 48 hours after treatment, it was gradually increased in the CBP group compared with those on ICU admission and at 12 hours after treatment ( P<0.05), while in the non-CBP group, it continued to decrease ( P<0.05). The levels of TNF-α, IL-6 and IL-10 on ICU admission were (51.6±17.1)pg/ml, (174.1±57.3)pg/ml and (67.6±16.2)pg/ml respectively in the CBP group and (49.5±16.7)pg/ml, (177.8±58.7)pg/ml and (65.7±16.6)pg/ml respectively in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the levels of TNF-α in the CBP group were (43.6±15.6)pg/ml, (29.4±12.5)pg/ml and (26.2±10.6)pg/ml respectively, the IL-6 levels were (122.4±41.7)pg/ml, (90.6±33.1)pg/ml, (75.6±24.7)pg/ml respectively and the IL-10 levels were (72.6±18.1)pg/ml, (80.7±20.6)pg/ml, (86.2±22.9)pg/ml respectively, which were significantly lower than (48.8±16.2)pg/ml, (46.5±15.5)pg/ml, (40.0±14.2)pg/ml at 12 hours after treatment, (168.4±51.6)pg/ml, (131.5±42.7)pg/ml, (112.7±35.8)pg/ml at 24 hours after treatment, and (78.6±19.3)pg/ml, (91.1±23.8)pg/ml, (99.4±26.6)pg/ml at 48 hours after treatment in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the levels of TNF-α and IL-6 in both groups continued to decrease, while the levels of IL-10 continued to increase compared with those on ICU admission ( P<0.05). On ICU admission, the APACHE Ⅱ and SOFA scores were (20.6±10.5)points and (6.2±1.9)points in the CBP group and (21.2±11.2)points and (6.7±2.1)points in the non-CBP group ( P>0.05). At 48 hours after treatment, the APACHE Ⅱ and SOFA scores were (13.5±6.6)points and (2.7±0.6)points in the CBP group, which were significantly lower than (18.3±9.3)points and (5.3±1.5)points in the non-CBP group ( P<0.01). At 48 hours after treatment, the APACHE II and SOFA scores in both groups were significantly decreased compared with those on ICU admission ( P<0.05 or 0.01). The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were (13.0±5.7)days, (20.4±8.6)days and 19.2% (10/52) respectively, which were significantly shorter and smaller than (17.6±6.6)days, (26.5±9.4)days and 31.6% (12/38) in the non-CBP group ( P<0.05 or 0.01). Conclusions:CBP treatment may reduce the release of mtDNA by alleviating the mitochondrial damage of the mononuclear cells in patients with traumatic sepsis so that the release of inflammatory factors and cellular apoptosis is reduced, and improve the state of cell energy metabolism and cellular immune function by increasing the activity of mitochondrial respiratory chain complex V in the mononuclear cells, and participate in the reconstruction of immune homeostasis of the body so the inflammatory state and clinical prognosis of the patients are improved.

Objective:To investigate the effects of astragaloside IV (AS-IV) on acute myocardial injury in rats with high-level spinal cord injury (SCI).Methods:Twenty-four healthy male SD rats, aged 8-10 weeks with a body weight of 250-300 g, were randomly divided into 4 groups using a random number table method: sham operation group, high-level SCI group (SCI group), high-level SCI+AS-IV group (SCI+AS-IV group) and high-level SCI+AS-IV+silent information regulator 1 (SIRT1) inhibitor EX527 group (SCI+AS-IV+EX527 group), with 6 rats in each group. The SCI model was established using the modified Allen method and the sham operation group underwent the spinal cord exposure only. In the SCI+AS-IV group, 40 mg/kg of AS-IV was injected intraperitoneally immediately after injury. SCI+AS-IV+EX527 group received an intraperitoneal injection of 5 mg/kg EX527 at one hour before injury and another injection of 40 mg/kg AS-IV in the same way immediately after injury. The sham operation group and the SCI group received an equal volume of saline via intraperitoneal injection. Immediately after awakening from injury, the hind limb motor function of the rats in each group was observed, recorded and then evaluated using the BBB method. At 24 hours after injury, the ultrastructure of the cardiomyocytes was examined under a transmission electron microscope; the levels of serum cardiac troponin I (cTnI), myocardial tissue inflammatory factors interleukin (IL)-18 and IL-1β were quantified by the ELISA method; the level of reactive oxygen species (ROS) of the myocardial tissue was assessed utilizing the dihydroethidium (DHE) assay; biochemical analyses were employed to determine the superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentrations; mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD), SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) were examined using RT-PCR and Western blot; cardiomyocyte pyroptosis rate was evaluated by caspase-1 and TUNEL double-labeled fluorescence staining.Results:Immediately after awakening from injury, the sham operation group exhibited normal hind limb activity, with BBB scores of 21(21, 21)points, while the remaining groups displayed flaccid paralysis in both hind limbs, accompanied by the cessation of spontaneous excretion, with BBB scores of 0(0, 0)points. At 24 hours after injury, transmission electron microscopy did not reveal any significant abnormalities in the ultrastructure of the myocardiomyocytes in the sham operation group, while changes of varying degrees were observed in the SCI group. The ELISA results indicated that at 24 hours after injury, the serum cTnI level in the SCI group was (1 435.3±148.1)pg/ml, higher than (619.6±95.4)pg/ml in the sham operation group ( P<0.01); the cTnI level was (1 154.0±80.0)pg/ml in the SCI+AS-IV group, lower than that in the SCI group ( P<0.01); the cTnI level was (1 321.8±50.2)pg/ml in the SCI+AS-IV+EX527 group, higher than that in the SCI+AS-IV group ( P<0.05). The levels of IL-18 and IL-1β in the myocardial tissue in the SCI group were (493.0±145.0)pg/ml and (936.7±93.2)pg/ml, higher than (131.1±62.5)pg/ml and (281.7±83.6)pg/ml in the sham operation group ( P<0.01); the levels of IL-18 and IL-1β in the SCI+AS-IV group were (182.4±45.6)pg/ml and (573.4±99.5)pg/ml, lower than those in the SCI group ( P<0.01); the levels of IL-18 and IL-1β in the SCI+AS-IV+EX527 group were (337.4±72.0)pg/ml and (742.6±82.7)pg/ml, higher than those in the SCI+AS-IV group ( P<0.05), yet lower than those in the SCI group ( P<0.01). At 24 hours after injury, DHE and biochemical assays showed that the levels of ROS and MDA in the myocardial tissue in the SCI group were (65±6)% and (1.97±0.27)nmol/mg, higher than (19±10)% and (1.03±0.16)nmol/mg in the sham operation group ( P<0.01); the ROS and MDA levels in the SCI+AS-IV group were (37±10)% and (1.39±0.11)nmol/mg, lower than those in the SCI group ( P<0.01); the ROS and MDA levels in the SCI+AS-IV+EX527 group were (52±7)% and (1.70±0.14)nmol/mg, higher than those in the SCI+AS-IV group ( P<0.05). The SOD level in the myocardial tissue of the SCI group was (658.48±77.56)U/mg, lower than (1 059.55±71.91)U/mg in the sham operation group ( P<0.01); the SOD level in the SCI+AS-IV group was (901.74±32.30)U/mg, higher than that in the SCI group ( P<0.01); the SOD level in the myocardial tissue in the SCI+AS-IV+EX527 group was (799.86±26.70)U/mg, lower than that in the SCI+AS-IV group ( P<0.05). At 24 hours after injury, RT-PCR showed that the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue of the SCI group were 2.07±0.25, 2.46±0.28 and 1.82±0.12 respectively, which were higher than 1.10±0.13, 0.95±0.17 and 1.03±0.08 in the sham operation group ( P<0.01); the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV group were 1.47±0.24, 1.51±0.16 and 1.42±0.13 respectively, which were lower than those in the SCI group ( P<0.01); the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV+EX527 group were 1.93±0.28, 1.97±0.31 and 1.65±0.16 respectively, which were higher than those in the SCI+AS-IV group, yet lower than those in the SCI group ( P<0.05). The mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI group were 0.41±0.09 and 0.56±0.07, lower than 1.20±0.14 and 1.29±0.20 in the sham operation group ( P<0.01); the mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV group were 0.78±0.08 and 1.01±0.19, higher than those of the SCI group ( P<0.01); the mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue of the SCI+AS-IV+EX527 group were 0.53±0.12 and 0.72±0.22, lower than those of the SCI+AS-IV group ( P<0.05). At 24 hours after injury, the western blot analysis showed that the protein expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue in the SCI group were 1.00±0.20, 0.60±0.19 and 0.77±0.15 respectively, which were higher than 0.27±0.09, 0.18±0.10 and 0.28±0.08 in the sham operation group ( P<0.01); the protein expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV group were 0.59±0.10, 0.25±0.11 and 0.33±0.11 respectively, lower than those in the SCI group ( P<0.01); the protein expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue in the SCI+AS-IV+EX527 group were 0.85±0.15, 0.54±0.12 and 0.55±0.13 respectively, higher than those in the SCI+AS-IV group ( P<0.05). The protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI group were 0.44±0.16 and 0.28±0.10, lower than 0.93±0.22 and 0.75±0.16 in the sham operation group ( P<0.01); the protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV group were 0.78±0.19 and 0.55±0.12, higher than those in the SCI group ( P<0.01); the protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV+EX527 group were 0.46±0.16 and 0.35±0.07, lower than those in the SCI+AS-IV group ( P<0.05). At 24 hours after injury, caspase-1 and TUNEL double-labeled fluorescence staining showed that the cardiomyocyte pyroptosis rate in the SCI group was (34.5±6.7)%, higher than (5.3±2.9)% in the sham operation group ( P<0.01); the cardiomyocyte pyroptosis rate in the SCI+AS-IV group was (13.4±3.0)%, lower than that in the SCI group ( P<0.01); the cardiomyocyte pyroptosis rate in the SCI+AS-IV+EX527 group was (22.5±5.9)%, higher than that in the SCI+AS-IV group ( P<0.01), yet lower than that in the SCI group ( P<0.01). Conclusions:AS-IV can significantly reduce acute myocardial injury in rats with high-level SCI. Its mechanism may involve activating the myocardial SIRT1/PGC-1α signaling pathway, protecting the mitochondria, enhancing the ability to resist oxidative stress, and effectively inhibiting the NLRP3 inflammasome-mediated pyroptosis pathway.