This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*

This study was designed to investigate the effect of dihydromyricetin (DHM) on inducing apoptosis of ovarian cancer cells A2780 through endoplasmic reticulum stress (ERS) pathway and the mechanisms involved in vitro and in vivo. A2780 cells were treated with different concentrations of DHM, and the protein expression levels of glucose-regulated protein 78 (GRP78) which is related to ERS increased, apoptotic proteins C/EBP-homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase-12) elevated. After pretreatment with ERS inhibitor, 4-phenyl butyric acid (4-PBA), following the intervention with DHM, the A2780 cell viability decreased and apoptotic rate increased. All animal welfare and experimental procedures were approved by the Animal Ethics Committee of Chongqing Medical University. Intraperitoneal injection of DHM suspension into nude mice with ovarian cancer could significantly inhibit the growth of transplanted tumor in vivo, increase the protein expression levels of GRP78, CHOP, and caspase-3. Moreover, swollen and broken endoplasmic reticulum could be observed in tumor tissues, suggesting that DHM intervention induces apoptosis mediated by ERS. The results indicated that DHM could induce apoptosis of ovarian cancer cells and inhibit the growth of transplanted tumors in nude mice, which might be related to the activation of ERS pathway.

OBJECTIVE: To assess the effect of neutralizing CD96 on natural killer (NK) cell functions in mice with pulmonary infection and explore the possible mechanism. METHODS: Male BALB/c mice were randomly divided into infection group (Cm group), anti-CD96 treatment group (anti-CD96 group) and control group (=5). In the former two groups, was inoculated intranasal administration to establish mouse models of pulmonary infection, and the mice in the control group received intranasal administration of the inhalation buffer. In anti-CD96 group, the mice were injected with anti-CD96 antibody intraperitoneally at the dose of 250 μg every 3 days after the infection; the mice in Cm group received intraperitoneal injections of saline. The body weight of the mice was recorded daily. The mice were sacrificed 5 days after infection, and CD96 expression was detected by quantitative real-time PCR and Western blotting. HE staining and pathological scores were used to evaluate pneumonia of the mice. The inclusion body forming units (IFUs) were detected in the lung tissue homogenates to assess lung tissue chlamydia load. Flow cytometry and ELISA were used to assess the capacity of the lung NK cells to produce interferon-γ (IFN-γ) and regulate macrophages and Th1 cells. RESULTS: infection inhibited CD96 expression in NK cells of the mice. Compared with those in Cm group, the mice in antiCD96 mice showed significantly milder lung inflammation ( < 0.05) and reduced chlamydia load in the lung tissue ( < 0.05). Neutralizing CD96 with anti-CD96 significantly enhanced IFN-γ secretion by the NK cells ( < 0.05) and augmented the immunoregulatory effect of the NK cells shown by enhanced responses of the lung macrophages ( < 0.05) and Th1 cells ( < 0.05). CONCLUSIONS Inhibition of CD96 alleviates pneumonia in -infected mice possibly by enhancing IFN-γ secretion by NK cells and augmenting the immunoregulatory effect of the NK cells on innate and adaptive immunity.
Animals ; Antigens, CD ; metabolism ; Chlamydia Infections ; complications ; immunology ; physiopathology ; Chlamydia muridarum ; Interferon-gamma ; genetics ; metabolism ; Killer Cells, Natural ; metabolism ; Lung Injury ; etiology ; genetics ; prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL

OBJECTIVE: To assess the effect of neutralizing CD96 on natural killer (NK) cell functions in mice with pulmonary infection and explore the possible mechanism. METHODS: Male BALB/c mice were randomly divided into infection group (Cm group), anti-CD96 treatment group (anti-CD96 group) and control group (=5). In the former two groups, was inoculated intranasal administration to establish mouse models of pulmonary infection, and the mice in the control group received intranasal administration of the inhalation buffer. In anti-CD96 group, the mice were injected with anti-CD96 antibody intraperitoneally at the dose of 250 μg every 3 days after the infection; the mice in Cm group received intraperitoneal injections of saline. The body weight of the mice was recorded daily. The mice were sacrificed 5 days after infection, and CD96 expression was detected by quantitative real-time PCR and Western blotting. HE staining and pathological scores were used to evaluate pneumonia of the mice. The inclusion body forming units (IFUs) were detected in the lung tissue homogenates to assess lung tissue chlamydia load. Flow cytometry and ELISA were used to assess the capacity of the lung NK cells to produce interferon-γ (IFN-γ) and regulate macrophages and Th1 cells. RESULTS: infection inhibited CD96 expression in NK cells of the mice. Compared with those in Cm group, the mice in antiCD96 mice showed significantly milder lung inflammation ( < 0.05) and reduced chlamydia load in the lung tissue ( < 0.05). Neutralizing CD96 with anti-CD96 significantly enhanced IFN-γ secretion by the NK cells ( < 0.05) and augmented the immunoregulatory effect of the NK cells shown by enhanced responses of the lung macrophages ( < 0.05) and Th1 cells ( < 0.05). CONCLUSIONS Inhibition of CD96 alleviates pneumonia in -infected mice possibly by enhancing IFN-γ secretion by NK cells and augmenting the immunoregulatory effect of the NK cells on innate and adaptive immunity.
Animals ; Antigens, CD ; Chlamydia Infections ; Chlamydia muridarum ; Interferon-gamma ; Killer Cells, Natural ; Lung Injury ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL

Antineoplastic Agents/therapeutic use* ; Dasatinib/therapeutic use* ; Humans ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Prognosis ; Protein Kinase Inhibitors ; Treatment Outcome

Objective To investigate the diagnostic value of CT and MRI in struma ovarii (SO).Methods Imaging features of 9 cases with SO confirmed by pathology were analyzed retrospectively.9 patients underwent CT,3 cases underwent both CT and MRI, which were both pre-and post-contrast enhancement.The location,size,shape,margin,density or signal intensity of the lesion,as well as the enhancement patterns of the cystic wall and solid components were observed.Results 7 tumors were located in the right ovary and 2 in the left,with smooth margins and clear boundary.The diameters of the lesions were 5-1 5 cm.The tumors were round in 2 cases,oval round in 2 cases and irregular in 5 cases.9 tumors all appeared cystic-solid type,mainly muti-cystic.The cystic components showed heterogeneous density on CT,mostly low signal intensity on T1WI and high signal intensity on T2WI,few cystic components showed high signal intensity on both T1WI and T2WI.Calcifications were found in 3 cases and fat in 2 cases.The solid components showed slightly high density on plain CT scanning and enhanced markedly either on CT or MRI.6 cases were accompanied with hysteromyomas and 2 cases with ovarian embryoma in the contralateral ovary.Conclusion CT and MRI appearances of SO have a certain characteristic,often manifested as a unilateral adnexal cystic-solid mass and the solid components obviously enhancement,but the boundary is smooth and clear.CT and MRI have different advantages.

Objective To explore the manifestations and diagnostic value of CT and MRI in gynecological acute abdomen.Methods CT and MRI features of 45 patients with gynecological acute abdomen proved by surgery were reviewed,including 17 ectopic pregnancy,10 ovarian cyst rupture,6 pedicle torsion of ovarian tumors,9 tubo-ovarian abscess and pelvic inflammation and 3 uterine perforation.31 cases underwent CT examination,14 cases underwent MRI examination and 39 cases underwent non-enhancement and enhancement scanning.Results In the 17 ectopic pregnancy cases,cystic structure surrounded by a thick wall or heterogeneous mass located in adnexal area was found,with 10 cases showing increased number of peripheral vessels penetrating into tumors.In the 10 cases with rupture of ovarian cyst, thick capsule wall was incomplete and cystic cavities collapsed in 7 lesions.In the 6 cases with pedicle torsion of ovarian tumors,irregular thickening of tumor pedicle were found in 4 cases,ovarian enlargement with surrounding follicles arrayed as fruit platter were found in 2 cases.In the 9 cases with tubo-ovarian abscess and pelvic inflammation,honeycomb-shaped lesions and multilocular changes were found in 6 cases and fallopian tube expanded like sausages in 5 cases.3 cases with uterine perforation exhibited intrauterine gas and fluid.Uterus with overflowed gas was found in 2 cases.One case had the thin and incomplete uterine wall.Conclusion CT and MRI can be used to confirm the causes of gynecological acute abdomen,and to comprehensively display the anatomical structures and pathological changes of pelvic tissues and organs.Therefore,CT and MRI are effective supplement means for the clinical diagnosis of gynecological acute abdomen.

Objective To study the clinical application effects of nasal high flow humidification oxygen therapy in patients with chronic obstructive pulmonary disease (COPD). Methods A total of 98 COPD patients hospitalized in PLA 81 Hospital from January to December 2016 were included in the study using convenient sampling method. Patients were randomly divided into the observation group and the control group, 49 cases respectively. Patients in the observation group received nasal high flow humidification oxygen therapy, while patients in the control group used common humidification oxygen bottle. Respiratory function indexes and the mucus viscosity were measured and compared between two groups before and after the intervention. Results Before the intervention, there were no statistically significant differences in respiratory function indexes between two groups (P> 0.05). After the intervention, there were significant differences in the respiratory frequency, PaO2, PaCO2, SaO2, heart rate, Clinical Pulmonary Infection Score between two groups (P< 0.05). Before the intervention, no significant difference in the mucus viscosity was observed between two groups (P> 0.05); at 24 h and 72 h after the intervention, significant difference in the mucus viscosity was observed between two groups (P< 0.05). Conclusions Nasal high flow humidification oxygen therapy can improve the respiratory function and airway humidification of COPD patients when compared to normal humidification oxygen therapy. Thus, it is worthy of clinical promoting.

OBJECTIVE: To observe the effect of "Xingnao Kaiqiao" acupuncture(acupuncture technique for restoring consciousness) combined with hyperbaric oxygen in patients with hypoxic ischemic encephalopathy and assess its influence on blood rheology. METHODS: Forty patients with hypoxic ischemic encephalopathy were randomly divided into treatment group and control group with 20 cases in each group. The treatment group received "Xingnao Kaiqiao" acupuncture combined with hyperbaric oxygen, and the control group received hyperbaric oxygen only. The two groups of patients were treated once per day for 6 consecutive days, which consisted of one course of treatment, and the total treatment lasted for four courses. Before and after treatment, the patients underwent the mini mental state examination (MMSE) to evaluate cognitive function and the barthel index score for activities of daily living. The changes of whole blood viscosity, plasma viscosity, and erythrocyte aggregation index were determined. RESULTS: After treatment, both the treatment and control groups showed improvements in cognitive function，activities of daily living, and blood rheology compared with those before treatment (P<0.05). However, these improvements in the treatment group were significantly greater than those in the control group (P<0.05). CONCLUSIONS: Application of "Xingnao Kaiqiao" acupuncture combined with hyperbaric oxygen in patients with hypoxic ischemic encephalopathy can result in an integrated curative effect, a significant improvement in the blood rheology indexes, and promote the recovery of brain cells.