Objective To observe the clinical effects of Xie's Feiai No.1 formula on patients with advanced non-small cell lung cancer (NSCLC) and its influence on body immune system, VEGF (blood vessel endothelia growth factor) and CYFRA21-1 (keratoprotein 21-1). Methods 650 cases of advanced NSCLC were randomized into a treatment group and chemotherapy group, with 350 cases and 300 cases in each group respectively. The treatment group was administrated with Xie's Feiai No.1 formula, while the chemotherapy group was treated with chemotherapy ofGP plan/TP plan. Both groups were treated for 2 months. Results The short-term effective rate was 56.57% in the treatment group, which was superior to 44.33% (P<0.01) in the chemotherapy group; Steady rate KPS score improvement was 85.14% in the treatment group, which was also higher than 27.00% (P<0.01) in the chemotherapy group; besides the levels of total T cell, adjuvant T cell and NK cell in the treatment group were higher than the chemotherapy group, while the levels of Ts cell, VEGF and CYFRA21-1 int the treatment group were lower than the chemotherapy group. Long-term efficacy observation showed that the survival rate of 117 cases with advanced NSCLC was 83.59% in one year and 46.27% in three years in the treatment group, both significantly higher than those in the chemotherapy group (P<0.01).Conclusion Xie's Feiai No.l formula can increase NSCLC patients' survival time, improve quality of life, strengthen immunological function and restrain tumor cells' activities.

Neonatal infection related diseases are the main causes of neonatal death and disability.Traditional inflammatory factors, such as peripheral blood leucocyte count, C-reactive protein and procalcitonin play an important role in indicating neonatal infectious diseases.However, its sensitivity, specificity and effectiveness still need to be improved.Many studies have shown that the expression of serum amyloid A(SAA)increase significantly in various infectious diseases of neonates, and it has received more and more attention as a new type of infection-related indicator.This article reviews the research progress on the structural characteristics of serum amyloid A, detection methods and its clinical application in various neonatal infectious diseases, follow-up of disease changes, guidance of antibiotic use and evaluation of prognosis.

Objective    To explore the natural changes of procalcitonin (PCT) in the early period after pediatric cardiac surgery with cardiopulmonary bypass (CPB). Methods    A prospective and observational study was done on patients below 3 years of age, who underwent cardiac surgery involving CPB, with the risk adjustment of congenital heart surgery (RACHS) score of 2 to 5 and free from active preoperative infection or inflammatory disease. Blood samples for measurement of PCT, C-reactive protein (CRP) and white blood cell (WBC) were taken before surgery and daily for 7 days in postoperative period. Infections and complications within 7 days after operation were investigated. According to the presence or absence of infection and complications within 7 days after operation, the enrolled children were divided into an infection+complications group, a simple infection group, a simple complication group, and a normal group. Results     Finally, 429 children with PICU stay≥ 4 days were enrolled, including 268 males and 161 females, with a median age of 8.0 (0.7, 26.0) months. There were 145 children in the simple infection group, 38 children in the simple complication group, 230 children in the normal group and 16 children in the infection+complications group. The levels of PCT, CRP and WBC were significantly higher after CPB. CRP and WBC peaked on the second postoperative day (POD) and remained higher than normal until POD7. PCT peaked on POD1 and would generally decrease to normal on POD5 if without infection and complications. Age, body weight, RACHS scores, the duration of CPB and aortic cross-clamping time were correlated with PCT level. There was a statistical difference in PCT concentration between the simple infection group and the normal group on POD 3-7 (P<0.01) and a statistical difference between the simple complication group and the normal group on POD 1-7 (P<0.01). A statistical difference was found between the simple infection group and the simple complication group in PCT on POD 1-5 (P<0.05). Conclusion    WBC, CRP and PCT significantly increase after CPB in pediatric cardiac surgery patients. The factors influencing PCT concentration include age, weight, RACHS scores, CPB and aortic cross-clamping time, infection and complications.

OBJECTIVE: To evaluate the effects of ferroptosis in hippocampal neurons on cognitive dysfunction in rats with sepsis-associated encephalopathy (SAE) and its potential molecular mechanisms. METHODS: (1) Screening experiment of SAE modeling conditions: 42 healthy male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group (n = 6) and lipopolysaccharide (LPS) 5, 15, 30 mg/kg groups (each n = 12) according to the random number table method. The SAE modeling conditions were determined by survival and the changes in mean arterial pressure (MAP) and heart rate (HR) within 72 hours, the percentage of stiffness status, the levels of serum inflammatory factors including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), neuron specific enolase (NSE, a marker of neuronal injury), serum iron and lactic acid (Lac) contents, and the morphological changes in CA1 of hippocampus after 72 hours. (2) Deferoxamine (Def) intervention experiment: according to the results of screening experiments, 28 healthy male SD rats were divided into NS control group (n = 8), SAE group (n = 10) and Def+SAE group (n = 10) according to the random number table method. In the Def+SAE group, 100 mg/kg Def was injected intraperitoneally 12 hours before the modeling, once every 12 hours, with a total of 7 times; the rats in the NS control group and SAE group were injected with the same amount of NS. Then the cognitive function of rats was evaluated by fear conditioning test for the percentage of stiffness status; serum IL-6, TNF-α and NSE levels were determined by enzyme-linked immunosorbent assay (ELISA); the levels of serum Lac, serum iron and hippocampal malondialdehyde (MDA) and iron contents were determined by chemical colorimetric; the protein expressions of nuclear factor E2 related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and NAPDH oxidase 1 (NOX1) in hippocampus were determined by Western Blot; morphological changes in hippocampal CA1 were observed after hematoxylin and eosin (HE) staining. RESULTS: (1) Compared with the NS control group, intraperitoneal injection of 15 mg/kg LPS could significantly reduce the MAP and HR as time prolonged, and the reduction was most significant at 72 hours. The 72-hour survival rate was significantly reduced and cognitive function was impaired. The levels of serum IL-6, TNF-α, Lac and NSE were increased while the serum iron content was decreased significantly. The morphology of vertebral cells in hippocampal CA1 was irregular and some of the cells were obviously vacuolated. In the LPS 5 mg/kg group, there were no significant changes in vital signs, inflammation, organ function or cognitive dysfunction, while the symptoms of septic shock were apparent in the LPS 30 mg/kg group. Therefore, SAE model was reproduced by intraperitoneal injection of 15 mg/kg LPS for 72 hours. (2) Compared with the NS control group, the percentage of stiffness in the SAE group was significantly reduced. The levels of serum IL-6, NSE and hippocampal MDA, iron were significantly increased. The serum iron contents and hippocampal Nrf2 and GPX4 protein expressions were significantly reduced, while the hippocampal NOX1 protein expression was significantly increased. The morphology of vertebral cells in hippocampal CA1 was irregular and the cytoplasm was deeply stained. The results indicated that the level of oxidative stress in the hippocampus of SAE rats was increased, the neuron degenerations were obvious, and the cognitive function of rats were impaired. Compared with the SAE group, the percentage of stiffness in the Def+SAE group was significantly increased [(63.4±6.4)% vs. (47.6±6.0)%, P < 0.05]. The levels of serum IL-6, NSE, iron and hippocampal MDA, iron were significantly reduced [serum IL-6 (ng/L): 73.14±8.31 vs. 99.86±12.37, serum NSE (μg/L): 3.67±0.51 vs. 5.92±0.79, serum iron (mg/L): 68.43±8.12 vs. 134.60±15.63, hippocampal MDA (mol/g): 4.62±0.90 vs. 6.62±0.84, hippocampal iron (μg/g): 155.32±17.86 vs. 221.54±27.54, all P < 0.05]. The hippocampal protein expressions of Nrf2 and GPX4 were significantly increased [Nrf2/β-actin: 0.41±0.07 vs. 0.18±0.03, GPX4/β-actin: 0.74±0.09 vs. 0.40±0.06, all P < 0.05] while the hippocampal NOX1 protein expression was significantly reduced (NOX1/β-actin: 0.62±0.08 vs. 1.11±0.16, P < 0.05). The vertebral cells was significantly improved as compared with the SAE group. These findings showed that the oxidative stress level in hippocampus of the Def+SAE group was reduced, neuron degeneration was significantly alleviated, and the cognitive function of the rats was significantly improved. CONCLUSIONS The cognitive function of rats with SAE was significantly impaired, the hippocampal neurons were obviously damaged and ferroptosis was increased. Def pretreatment could significantly reduce iron deposition and ferroptosis in hippocampal neurons of SAE rats and improve cognitive dysfunction, which may be related to activation of Nrf2/GPX4 signaling pathway.
Animals ; Cognitive Dysfunction ; Ferroptosis ; Hippocampus ; Male ; NF-E2-Related Factor 2/metabolism* ; Neurons ; Rats ; Rats, Sprague-Dawley ; Sepsis ; Sepsis-Associated Encephalopathy ; Signal Transduction ; Tumor Necrosis Factor-alpha

Objective    To investigate the timing and clinical efficacy of diaphragmatic plication in the treatment of diaphragmatic paralysis after congenital heart disease (CHD) operation. Methods    From January 2013 to February 2019, 30 children with CHD who were treated in Fuwai Hospital were collected, including 17 males and 13 females with a median age of 19.5 (3, 72) months. There were 6 patients with bilateral diaphragmatic paralysis (bilateral group) and 24 patients with unilateral diaphragmatic paralysis (unilateral group). The clinical data of the two groups were compared. Results    Among the 6 bilateral diaphragmatic paralysis patients, 2 underwent bilateral diaphragmatic plication, and the other 4 patients continued their off-line exercise after unilateral diaphragmatic plication. Patients in the unilateral group had shorter ventilator use time (266.77±338.34 h vs. 995.33±622.29 h, P=0.001) and total ICU stay time (33.21±23.97 d vs. 67.33±28.54 d, P=0.008) than those in the bilateral group. One patient died in the bilateral group, and there was no statistical difference between the two groups (P=0.363). There was no statistical difference in the ICU stay time after diaphragm plication between the two groups (11.68±10.28 d vs. 29.83±27.73 d, P>0.05). Conclusion    Diaphragmatic plication is an effective treatment for diaphragmatic paralysis after CHD operation once the conservative treatment failed. The prognosis of bilateral diaphragmatic paralysis is worse than that of unilateral diaphragmatic paralysis. Strict control of indications for surgery is beneficial to the early recovery of patients.

Objective: To evaluate the effects of ferroptosis in hippocampal neurons on cognitive dysfunction in rats with sepsis-associated encephalopathy (SAE) and its potential molecular mechanisms. Methods: ① Screening experiment of SAE modeling conditions: 42 healthy male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group (n = 6) and lipopolysaccharide (LPS) 5, 15, 30 mg/kg groups (each n = 12) according to the random number table method. The SAE modeling conditions were determined by survival and the changes in mean arterial pressure (MAP) and heart rate (HR) within 72 hours, the percentage of stiffness status, the levels of serum inflammatory factors including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), neuron specific enolase (NSE, a marker of neuronal injury), serum iron and lactic acid (Lac) contents, and the morphological changes in CA1 of hippocampus after 72 hours. ② Deferoxamine (Def) intervention experiment: according to the results of screening experiments, 28 healthy male SD rats were divided into NS control group (n = 8), SAE group (n = 10) and Def+SAE group (n = 10) according to the random number table method. In the Def+SAE group, 100 mg/kg Def was injected intraperitoneally 12 hours before the modeling, once every 12 hours, with a total of 7 times; the rats in the NS control group and SAE group were injected with the same amount of NS. Then the cognitive function of rats was evaluated by fear conditioning test for the percentage of stiffness status; serum IL-6, TNF-α and NSE levels were determined by enzyme-linked immunosorbent assay (ELISA); the levels of serum Lac, serum iron and hippocampal malondialdehyde (MDA) and iron contents were determined by chemical colorimetric; the protein expressions of nuclear factor E2 related factor 2 (Nrf 2), glutathione peroxidase 4 (GPX4) and NAPDH oxidase 1 (NOX1) in hippocampus were determined by Western Blot; morphological changes in hippocampal CA1 were observed after hematoxylin and eosin (HE) staining. Results: ① Compared with the NS control group, intraperitoneal injection of 15 mg/kg LPS could significantly reduce the MAP and HR as time prolonged, and the reduction was most significant at 72 hours. The 72-hour survival rate was significantly reduced and cognitive function was impaired. The levels of serum IL-6, TNF-α, Lac and NSE were increased while the serum iron content was decreased significantly. The morphology of vertebral cells in hippocampal CA1 was irregular and some of the cells were obviously vacuolated. In the LPS 5 mg/kg group, there were no significant changes in vital signs, inflammation, organ function or cognitive dysfunction, while the symptoms of septic shock were apparent in the LPS 30 mg/kg group. Therefore, SAE model was reproduced by intraperitoneal injection of 15 mg/kg LPS for 72 hours. ② Compared with the NS control group, the percentage of stiffness in the SAE group was significantly reduced. The levels of serum IL-6, NSE and hippocampal MDA, iron were significantly increased. The serum iron contents and hippocampal Nrf 2 and GPX4 protein expressions were significantly reduced, while the hippocampal NOX1 protein expression was significantly increased. The morphology of vertebral cells in hippocampal CA1 was irregular and the cytoplasm was deeply stained. The results indicated that the level of oxidative stress in the hippocampus of SAE rats was increased, the neuron degenerations were obvious, and the cognitive function of rats were impaired. Compared with the SAE group, the percentage of stiffness in the Def+SAE group was significantly increased [(63.4±6.4)% vs. (47.6±6.0)%, P < 0.05]. The levels of serum IL-6, NSE, iron and hippocampal MDA, iron were significantly reduced [serum IL-6 (ng/L): 73.14±8.31 vs. 99.86±12.37, serum NSE (μg/L): 3.67±0.51 vs. 5.92±0.79, serum iron (mg/L): 68.43±8.12 vs. 134.60±15.63, hippocampal MDA (mol/g): 4.62±0.90 vs. 6.62±0.84, hippocampal iron (μg/g): 155.32±17.86 vs. 221.54±27.54, all P < 0.05]. The hippocampal protein expressions of Nrf 2 and GPX4 were significantly increased [Nrf 2/β-actin: 0.41±0.07 vs. 0.18±0.03, GPX4/β-actin: 0.74±0.09 vs. 0.40±0.06, all P < 0.05] while the hippocampal NOX1 protein expression was significantly reduced (NOX1/β-actin: 0.62±0.08 vs. 1.11±0.16, P < 0.05). The vertebral cells was significantly improved as compared with the SAE group. These findings showed that the oxidative stress level in hippocampus of the Def+SAE group was reduced, neuron degeneration was significantly alleviated, and the cognitive function of the rats was significantly improved. Conclusions The cognitive function of rats with SAE was significantly impaired, the hippocampal neurons were obviously damaged and ferroptosis was increased. Def pretreatment could significantly reduce iron deposition and ferroptosis in hippocampal neurons of SAE rats and improve cognitive dysfunction, which may be related to activation of Nrf 2/GPX4 signaling pathway.

This study aims to gain insight into the DNA-specific recognition mechanism of c-Myb transcription factor during the regulation of cell early differentiation and proliferation. Therefore, we chose the chicken myeloid gene, mitochondrial import protein 1 (mim-1), as a target to study the binding specificity between potential dual-Myb-binding sites. The c-Myb-binding site in mim-1 is a pseudo-palindromic sequence AACGGTT, which contains two AACNG consensuses. Simulation studies in different biological scenarios revealed that c-Myb binding with mim-1 in the forward strand (complex F) ismore stable than that inthereverse strand (complex R). The principal component analysis (PCA) dynamics trajectory analyses suggested an opening motion of the recognition helices of R2 and R3 (R2R3), resulting in the dissociation of DNA from c-Myb in complex R at 330 K, triggered by the reduced electrostatic potential on the surface of R2R3. Furthermore, the DNA confirmation and hydrogen-bond interaction analyses indicated that the major groove width of DNA increased in complex R, which affected on the hydrogen-bond formation ability between R2R3 and DNA, and directly resulted in the dissociation of DNA from R2R3. The steered molecular dynamics (SMD) simulation studies also suggested that the electrostatic potential, major groove width, and hydrogen bonds made major contribution to the DNA‍-specific recognition. In vitro trials confirmed the simulation results that c-Myb specifically bound to mim-1 in the forward strand. This study indicates that the three-dimensional (3D) structure features play an important role in the DNA-specific recognition mechanism by c-Myb besides the AACNG consensuses, which is beneficial to understanding the cell early differentiation and proliferation regulated by c-Myb, as well as the prediction of novel c-Myb-binding motifs in tumorigenesis.
Molecular Dynamics Simulation ; Consensus ; DNA ; Hydrogen