Objective To investigate whether mitogen-activated protein kinases(MAPKs),which were involved in changes in osmolali-ty,might mediate aquaporin-4(AQP4)expression in astrocytes after oxygen-glucose deprivation(OGD)in rats.Methods Astrocytes were obtained from new born Sprague-Dawley rats.The P2cells were divided into control group,OGD group and inhibitors of U0126,SB203580 and SP600125 groups. The latter groups underwent OGD for five hours and reoxygenated, the inhibitors of U0126, SB203580 and SP600125(1 μmol/L and 10 μmol/L,respectively)groups,named U1,U10,SB1,SB10,SP1 and SP10 groups,respectively,were cultured with the inhibitors for twelve hours.The volume of cells in OGD group was measured half,one,one and half,two,three,four,eight and twelve hours after reoxygenation,and the expression of AQP4 was detected half,one,one and half,eight and twelve hours after reoxygen-ation with Western blotting.The expression of AQP4,and phosphorylation of extracellular regulated protein kinases(p-ERK),c-Jun N-termi-nal kinase(p-JNK)and p38 MAPK(p-p38 MAPK)was detected 24 hours after reoxygenation in all the groups,while the activity of lactate dehydrogenase(LDH)was measured.Results The volume of cells increased in OGD group one and half,two,three and four hours after re-oxygenation compared with those in the control group(P<0.001),and the expression of AQP4 also increased in OGD group after reoxygen-ation(P<0.001),especially 1.5 hours of reoxygenation.The expression of AQP4,p-ERK,p-JNK and p-p38 MAPK increased in OGD group after five hours of OGD compared with those in the control group(P<0.001),and the expression of p-ERK,p-JNK and p-p38 MAPK de-creased in the inhibitors groups compared with those in OGD group(P<0.001),and the expression of AQP4 decreased in SB10 group(P<0.001).The activity of LDH was less in all the inhibitors groups except SP1 and SB1 groups than in OGD group(P<0.01),and was the least in SB10 group (P<0.001). Conclusion MAPKs signal pathway, especially p38 MAPK, may promote AQP4 expression in astrocytes after OGD in rat,and play a role in cells death.

Objective:To evaluate the trauma center model in general hospitals for patients with severe trauma.Methods:The data of 1,248 patients with severe trauma (ISS≥16) were retrospectively analyzed who had been admitted to the trauma centers in 6 Chinese general hospitals from January 2019 through June 2020. They were 987 males and 261 females with an age of 50.4 years ± 15.4 years. Their injuries were caused by a traffic accident in 622 cases, falling from a height in 357 cases, a knife in 62 cases, and others (like a heavy object and fall) in 207 cases. Upon admission, their injury severity scores (ISS) were 24.9±8.5 and their Glasgow coma scores (GCS) 12.6±3.6. They were all treated in a scientific and standard manner by a multidisciplinary team at the trauma center of their specific general hospital. Recorded were deaths within 30 days after admission, 30-day mortality and causes of death.Results:All the patients were treated effectively. 101 deaths occurred within 30 days after admission, yielding a 30-day mortality of 8.1%. The main causes of death were severe craniocerebral injury in 56 cases, hemorrhagic shock in 26 cases, multi-organ failure in 11 cases and others in 8 cases.Conclusions:Establishment of trauma centers in China can make up for the disadvantage of over-division of clinical specialties in large general hospitals which has led to insufficient care for patients with severe trauma and multiple injuries. The trauma centers in general hospitals may be a feasible model to be popularized in treatment of patients with severe trauma and multiple injuries.

OBJECTIVE: To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism. METHODS: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. RESULTS: Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05). CONCLUSIONS YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.
AMP-Activated Protein Kinases/metabolism* ; Adrenocorticotropic Hormone ; Animals ; Comorbidity ; Depression/drug therapy* ; Energy Metabolism ; Interleukin-6/metabolism* ; Myocardial Infarction/pathology* ; Neurotransmitter Agents ; Rats ; Rats, Sprague-Dawley ; Serotonin/metabolism* ; Tablets ; Tumor Necrosis Factor-alpha/metabolism*

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide