Objective:To evaluate the effect of tubastatin A (TubA) on pyroptosis during brain injury after cardiac arrest and resuscitation in swine.Methods:Twenty-two conventional male white swine, weighing 34-39 kg, aged 4-6 months, were divided into 3 groups using a random number table: sham operation group (group S, n=6), cardiac arrest-cardiopulmonary resuscitation (CA-CPR) group ( n=8) and CA-CPR+ TubA group ( n=8). The swine model of CA-CPR was established by 9 min of cardiac arrest and 6 min of cardiopulmonary resuscitation in CA-CPR group and CA-CPR+ TubA group. TubA 4.5 mg/kg (in 50 ml of normal saline) was infused over 1 h via the femoral vein starting from 5 min after resuscitation in CA-CPR+ TubA group. Before developing the model and at 1, 2, 4 and 24 h after resuscitation (T 0-4), blood samples were collected from the femoral vein for determination of the concentrations of neuron specific enolase (NSE) and S100β protein in serum (by enzyme-linked immunosorbent assay). Neurological deficit score (NDS) was evaluated at T 4. The animals were then sacrificed, and their brain cortex tissues were harvested to measure the expression of histone deacetylase 6 (HDAC6), caspase-3, cleaved caspase-3, gasdermin E (GSDME) and GSDME N-terminal (N-GSDME) (by Western blot) and contents of high mobility group box 1 (HMGB1), interleukin-1β (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the serum concentrations of NSE and S100β were significantly increased at T 1-4, NDS was increased at T 4, the expression of HDAC6, caspase-3, cleaved caspase-3, GSDME and N-GSDME in brain cortex was up-regulated, and the contents of HMGB1, IL-1β and IL-18 were increased in CA-CPR and CA-CPR+ TubA groups ( P<0.05). Compared with group CA-CPR, the serum concentrations of NSE and S100β were significantly decreased at T 3, 4, NDS was decreased at T 4, the expression of HDAC6, caspase-3, cleaved caspase-3, GSDME and N-GSDME in brain cortex was down-regulated, and the contents of HMGB1, IL-1β and IL-18 were decreased in group CA-CPR+ TubA ( P<0.05). Conclusions:The mechanism by which TubA alleviates brain injury after cardiac arrest and resuscitation may be related to inhibition of pyroptosis in swine.

Uric acid is the end product of metabolism of purine which is synthesized in the body and from food.It is also an antioxidant in the body,and closely related to the bone,cardiovascular system,endocrine system,respiratory system,nervous system,urinary system,ophthalmology and otorhinolaryngology especially in the elderly.Therefore,more attentions should be paid to the relationship between hyperuricemia and senile diseases.Early screening and treatment of hyperuricemia might enable an improvement of the quality of life and even an extension of the life of older people.

Objective: To investigate the prevalence of physical activity and its influencing factors in rural residents in Shanxi and Chongqing. Methods: In four counties (districts) of Shanxi and Chongqing, local residents aged ≥18 who lived there for more than one year and had no plan to migrate to other areas in 2 years were surveyed through face to face questionnaire interviews to collect the information about their daily physical activity time, sedentary time, related knowledge and attitude, and others. Results: The physical inactivity rate of the residents was 14.9%, and 88.7% of residents never took daily physical activity. The average sedentary time was (3.91±2.06) hours. The results of multivariate analysis showed that education level, per capita monthly income and activity degree were the factors influencing physical inactivity. Conclusion: The proportion of people who never took daily physical activity in the survey area was higher than the average level in rural areas in China, so measures should be taken to improve the overall rate of physical activity. For people who have exercise willingness, but have no practice, and those who have already increased their physical activities, targeted guidance is needed on the basis of strengthened health education.
China ; Educational Status ; Exercise ; Health Education ; Humans ; Income ; Motivation ; Motor Activity ; Physicians ; Prevalence ; Rural Population ; Surveys and Questionnaires

OBJECTIVE: To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine. METHODS: Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting. RESULTS: After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (μmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05]. CONCLUSIONS TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.
Male ; Animals ; Swine ; Abdominal Injuries ; Apoptosis ; Cardiopulmonary Resuscitation ; Kidney Diseases