Wendantang Treats Inflammation in Obesity （Syndrome of Phlegm-dampness） by Regulating PI3K/Akt/mTOR Pathway-mediated Adipocyte Autophagy / 中国实验方剂学杂志

ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines， autophagy markers， and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the adipocytes of the rat model of obesity （syndrome of phlegm-dampness） and to explore the material basis of inflammation in obesity （syndrome of phlegm-dampness） and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups： 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity （syndrome of phlegm-dampness） for 8 weeks. After successful modeling， 48 obese rats were selected according to their body mass and randomized into a model control group， an orlistat （ORLI， 32.40 mg·kg-1） group， a rapamycin （RAPA， 2 mg·kg-1） group， and low-， medium-， and high-dose （4.45， 8.90， 17.80 g·kg-1， respectively） Wendantang groups， with 8 rats in each group. In addition， 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass， Lee's index， body fat ratio， and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 （ULK1）， Beclin1， human autophagy-related protein 5 （Atg5）， p62， and microtubule-associated protein 1 light chain 3 （LC3） Ⅰ/Ⅱ （markers of autophagy in adipocytes） was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， IL-4， IL-10， IL-13， and transforming growth factor （TGF）-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K， phosphatidylinositol triphosphate （PIP3）， Akt， mTORC1， ULK1， TSC1， and TSC2 in adipocytes. ResultCompared with the blank group， the modeling group showed increased body mass and Lee's index （P<0.01）， the obesity rate >20%， and phlegm-dampness syndrome manifestations such as physical obesity， decreased mobility， decreased appetite， lusterless and tight fur， loose stools， decreased responsiveness to the outside world， and decreased water intake. Compared with the normal control group， the model control group showed increased body mass， Lee's index， body fat ratio， adipocyte autophagy marker expression， pro- and anti-inflammatory cytokine levels （P<0.05， P<0.01）， down-regulated protein levels of classⅠ-PI3K， PIP3， Akt， mTORC1， TSC1， and TSC2 （P<0.01）， and up-regulated protein level of ULK1 （P<0.01）. The intervention groups showed lower body mass， body fat ratio， adipocyte autophagy marker protein expression， and protein levels of TNF-α， IL-6， IL-1β， MCP-1， IL-4， and IL-13 than the model control group （P<0.05， P<0.01）. Moreover， the RAPA and Wendantang （medium and high dose） groups showed lowered levels of IL-10 and TGF-β （P<0.01）， and the ORLI group showed down-regulated expression of TGF-β （P<0.01）. The expression of key molecules of the signaling pathway was up-regulated （P<0.05， P<0.01） while that of ULK1 was down-regulated （P<0.01） in all the intervention groups. Compared with the RAPA group， the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes （P<0.01）. In addition， the low-dose Wendantang group showed elevated levels of inflammatory cytokines （except TNF-α） （P<0.05， P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.05， P<0.01）. The levels of inflammatory cytokines （except IL-16， MCP-1， and IL-10） were elevated in the medium-dose Wendantang group （P<0.05， P<0.01）. The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups （P<0.05， P<0.01）. Compared with the ORLI group， low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes （P<0.01）， and the low-dose group showed elevated levels of inflammatory cytokines （IL-6， IL-4， and TGF-β） （P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.01）. The medium-dose Wendantang group showed up-regulated expression of IL-4 （P<0.01） and down-regulated expression of key molecules except PI3K of the signaling pathway （P<0.05， P<0.01）. The high-dose Wendantang group showed increased body mass， up-regulated expression levels of autophagy markers （ULK1， LC3 Ⅰ/Ⅱ） （P<0.05， P<0.01）， down-regulated expression of PIP3， mTORC1， and TSC1 （P<0.05， P<0.01）， and lowered levels of Beclin1， Atg5， TNF-α， and IL-13 （P<0.05， P<0.01）. ConclusionThe inflammation in obesity （syndrome of phlegm-dampness） is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.

Confusion and countermeasures of the non-conditioned anxiety test in rodent laboratory animals / 中华行为医学与脑科学杂志

Anxiety is a major mood disorder, and the high morbidity, co-morbidity and disability of anxiety disorders seriously affect people's quality of life, so the importance and urgency of research on anxiety cannot be overstated. Animal models are the main carriers for studying the mechanism of disease occurrence and development, drug efficacy evaluation and drug development.Unconditioned anxiety model is a common anxiety model.Elevated plus maze test, open field test and light-dark box test are widely accepted paradigms for the detection of unconditioned anxiety.This kind of behavioral paradigm based on environmental exposure takes advantage of the conflict between curiosity and fear of the unfamiliar environment to simulate and detect the anxiety of animals.However, the validity of these behavioral paradigms for evaluating anxiety in animals is questionable.In this paper, we discuss the concept of anxiety, the definition of anxiety behavior in the behavioral test of unconditioned anxiety, and the factors to be considered in the test of unconditioned anxiety behavior.On this basis, new solutions were proposed to the contradictions and blind spots in order to improve the test paradigm of anxiety behavior and provide a more reliable animal model for the evaluation of anxiety.This paper presents a new approach to address the contradictions and blind spots of this paradigm.

Expression of thyroid transcription factor 1 in patients with lung adenocarcinoma and its correlation with the prognosis of patients with advanced lung adenocarcinoma / 肿瘤研究与临床

Objective To analysis the expression of thyroid transcription factor 1 (TTF-1) in patients with lung adenocarcinoma, and discuss the relationship between TTF-1 expression and prognosis of patients with advanced lung adenocarcinoma. Methods A total of 786 cases of lung adenocarcinoma who were admitted to Xi'an Chest Hospital from January 2012 to June 2016 were selected. The expression of TTF-1 was detected by immunohistochemistry. The relationship between TTF-1 expression and patients ' clinicopathological features, treatment and survival were analyzed. Cox proportional hazard model was used to analyze the relationship between TTF-1 and prognosis of patients with advanced lung adenocarcinoma. Results Among 786 patients, 559 patients (71.12％) had positive TTF-1 expression, 227 patients (28.88％) had negative TTF-1 expression. The expression rates of TTF-1 in patients with well-differentiated, early stage, no lymph node metastasis, and no distant metastasis [77.26％ (197/255), 78.89％ (269/341), 78.95％ (225/285), and 75.61％(372/492)] were higher than those in patients with poorly differentiated, late stage, lymph node metastasis and distant metastasis 68.17％ (362/531), 65.17％ (290/445), 66.67％ (334/501), 63.60％ (187/294), the differenceswere statistically significant (χ 2 values were 6.917, 25.261, 13.339, and 12.911, all P < 0.05). The expressions of TTF-1 in primary lesions and metastatic lesions were consistent (κ = 0.894, P < 0.01). Among 385 patients with advanced lung adenocarcinoma who were unable to perform the operation, the proportion of epidermal growth factor receptor (EGFR) mutation in TTF-1 positive expression patients (45.60％, 109/239) was significantly higher than that in TTF-1 negative expression patients (26.02％, 38/146), and the difference was statistically significant (χ 2 = 14.721, P < 0.01). The median progression free survival (PFS) time of TTF-1 positive expression patients was significantly longer than that of TTF -1 negative expression patients (6.00 months vs. 4.20 months, P < 0.01), whether EGFR was mutation or not, the median PFS time of TTF-1 positive expression patients was significantly longer than that of TTF-1 negative expression patients (P =0.003; P < 0.01). TTF-1 expression (HR = 0.793, 95％ CI 0.639-0.984, P = 0.011) and EGFR gene status (HR =0.694, 95％ CI 0.432-0.864, P = 0.004) were independent influencing factors affecting the PFS of patients with advanced lung adenocarcinoma. Conclusions TTF-1 is widely expressed in lung adenocarcinoma and is associated with tumor differentiation, staging, lymph metastasis and distant metastasis. TTF-1 is a prognostic influencing factor in patients with advanced lung adenocarcinoma and can be used as a predictor of treatment for patients with advanced lung adenocarcinoma.

Focusing on the Construction of Research Base in Western Universities / 中华医学教育探索杂志

Research base is one of the key factors for subject construction.The current situations of research bases in western universities are not satisfactory due to terrain and history.Recognizing and improvement of the problems are very important for making them better to fit the needs of their development.It is the right time to cope with it.

Expression of Mdr1 gene in a murine bone marrow transplantation model / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of mdr1 gene in hematopoietic cells of a murine bone marrow transplantation model and to explore the feasibility of transferring mdr1 gene into hematopoietic cells to pro-vent myelosuppression from chemotherapy.</p><p><b>METHODS</b>mdr1 gene was transferred into hematopoietic cells of murine bone marrow by retrovirus vector. The expression and function of mdr1 gene in vivo was tested in a murine bone marrow transplantation model.</p><p><b>RESULTS</b>(1) mdr1 gene was successfully transferred into murine MNC, the transduction rate was 35%. (2) mdr1 gene transferred murine bone marrow transplantation model was established successfully by scheduled-bone marrow transplantation method. (3) In 1 approximately 5 months period, stable and effective expression of mdr1 gene could be detected in hematopoietic cells of the recipient mouse, the percentage of mdr1 gene expression cells in recipient's hematopoietic cells decreased monthly to 8.0%, 8.0%, 7.5%, 4.0% and 3.0%. (4) mdr1 expression hematopoietic cells had efficient resistance to chemotherapy.</p><p><b>CONCLUSION</b>It is an effective approach to transfer mdr1 gene into hematopoietic cells for preventing myelosuppression in chemotherapy.</p>

Changes of intracellular Ca~(2+) in living brain slices during focal cerebral ischemia/reperfusion / 中国病理生理杂志

AIM: The purpose of the present study was to detect intracellular Ca 2+ changes in living brain slices during focal cerebral ischemia/reperfusion (I/R) and reveal the role of intracellular Ca 2+ in the cerebral I/R injury. METHODS: The model of focal cerebral I/R was established in rats by reversible inserting a nylon thread, and dynamic change of intracellular Ca 2+ in brain slices was determined using laser confocal imaging system. RESULTS: ① Ca 2+ gradually enhanced with increase in ischemic time in cortex and striatum. ②At 1 h ischemia/ 10 min reperfusion, Ca 2+ increased significantly in striatum, but Ca 2+ decreased at 3 h reperfusion compared with 10 min reperfusion. ③ Ca 2+ markedly enhanced at 6 h ischemia compared with 1 h ischemia, and after 3 h reperfusion Ca 2+ decreased, but was still higher than that in sham-operation group. ④The striatum is more sensitive than cortex to ischemia/reperfusion. CONCLUSION: Ca 2+ overload in the area of cortex and striatum may play an important role in cerebral ischemia/reperfusion injury in rats.

A Long-term Follow-up of Neonatal Hypoxic-ischemic Encephalopathy / 中华围产医学杂志

Objective To study the clinical characteristics and long term prognosis of the neonates with hypoxic ischemic encephalopathy (HIE) and explore therapy to improve the prognosis. Methods Data of 1150 newborns with HIE were analyzed. retrospectively. Results There were 942 full term babies(81.9%) and 208 prematures(18.1%). Most of them were caused by anoxia occurring in intrauterine period or at birth, 75.0% of them with superimposed intracranial hemorrhage. The mortality rate was 7.0%(32.8% severe HIE, 4.2% moderate HIE). Among 852 surviors with follow up, the sequenlae rate is 10%(60.7% in severe HIE,4.5% in moderate HIE). The prognosis were bad. The therapy to improve the prognoses are as follow:(1)Early diagnosis and clinical intervention.(2)To maintein the hemostasis is the major principle of treatment.(3)To prevent organ function damage.(4)Long term(4 to 6 months) of Hyperbaric oxygen therapy should be applied to newborns with severe HIE.(5)Early follow up from newborn period and preventive intervention. Conclusion Prognoses of both newborn with sever HIE and prematures are bad. Long term treatment after newborn period is necessary to improve the prognosis.

Application of evidence-based medicine in the department of neurology / 中华医院管理杂志

Objective To explore ways of enhancing the therapeutic level of the neurology department and reducing the economic burdens of patients. Methods Relevant materials were collected by means of evidence based medicine to optimize therapeutic schedules, with cerebral infarction being the pitching in point. Results Prior to the adoption of evidence based medicine, the average length of stay, the effective rate of treatment and the expenses for single entity diseases were respectively 17.83?13.44, 89.91% and 4 550.70 yuan, whereas after the adoption of evidence based medicine, they were respectively 15.38?11.37, 94.16% and 3 942.88 yuan. Conclusion Evidence based management is a means of scientific management. Its application in the department of neurology has produced a marked effect and it is worthy to be spread.

Effects of glucose and Mg~(2+) in the neurons damaged by glutamate / 中国病理生理杂志

AIM and METHODS: To observe the effects of glucose-free and Mg 2+ -free in the extracellular fluid on the changes of [Ca 2+ ] i in the cerebro-cortical neurons damaged by 1 mmol/L glutamate using laser confocal scanning microscope. RESULTS: Both frequency and amplitude of neuronal calcium oscillation induced by glutamate were lowered in glucose-free and Mg 2+ -free buffers. The basic [Ca 2+ ] i concentration was lowered in the former case , but it was elevated in the latter case. CONCLUSION: Mg 2+ -free aggravates [Ca 2+ ] i overload induced by 1 mmol/L glutamate ,under certain conditions the glucose-free might resist damage role of glutamate and Mg 2+ -free.