Objective To investigate the effects of parecoxib sodium injection combined with dexmedetomidine hydrochloride injection on postoperative cognitive function and stress response in patients with osteoporotic compression fractures.Methods The patients with osteoporotic compression fractures were divided into treatment group and control group according to the treatment plan.The control group was given intravenous injection of dexmedetomidine hydrochloride injection 0.2 μg·kg-1load dose,then micro pump injection 0.2 μg·kg-1·min-1 maintenance dose,until 30 min before the end of the operation;patients in the treatment group were intravenously injected with parecoxib sodium injection 20 mg before local anesthesia and 30 min before the end of operation on the basis of the control group.The pain,sedation,hemodynamics[mean arterial pressure(MAP),heart rate(HR)],cognitive function and safety evaluation were compared between the two groups before operation(T0),2 h after operation(T1),6 h after operation(T2),12 h after operation(T3)and 24 h after operation(T4).Results There were 39 cases in the treatment group and 41 cases in the control group.Visual analogue scale(VAS)scores in treatment group and control group were(3.09±0.55)and(3.41±0.62)scores at T1;VAS scores were(3.02±0.57)and(3.35±0.48)scores at T2;VAS scores were(2.64±0.44)and(2.90±0.46)scores at T3;VAS scores were(2.02±0.41)and(2.35±0.47)scores at T4;MMSE scores were(25.28±1.57)and(24.33±1.42)scores at T2;MMSE scores were(28.16±1.01)and(27.25±0.89)scores at T4;MoCA scores were(24.63±1.60)and(23.59±1.25)scores at T2;MoCA scores were(27.20±0.97)and(26.48±0.83)scores at T4.There were statistically significant differences in the above indexes between the treatment group and the control group(all P＜0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,nausea vomiting and hypokalemia;adverse drug reactions in the control group included bradycardia,hypotension and nausea vomiting.The total incidence rates of adverse drug reactions were 12.82％and 9.76％,without statistically significant difference(P＞0.05).Conclusion Compared with using dexmedetomidine alone,parecoxib sodium combined with dexmedetomidine is beneficial for relieving postoperative pain in patients with osteoporotic compression fractures,improving postoperative cognitive function.

Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.

Aim To investigate the mechanism by which ginsenoside Rgl regulates autophagy anrl delays brain aging in mice through AMPK/mTOR signaling pathway.Methods C57BL/6J male mice were ran¬domly divided into four groups, namely brain aging model group ,control group, Rgl anti-aging group,auto¬phagy activator Rapamycin anti-aging group.After the modeling was completed, the test of each experimental index would be carried out on the next day.Morris wa¬ter maze experiment was used to detect the learning and memory ability of mice.Paraffin sections of the hippocampus were prepared, HE , Nissl and immunohis- tochemical staining were used to observe the morpholo¬gy of hippocampal neurons, the number of neurons and Nissl bodies was counted, and autophagy-related proteins p62 , ATG5 , ULK1 were detected.Brain tissue homogenates were prepared to detect the aetivity of brain tissue acetylcholinesterase ( AChE ).Western blot was userl to detect brain tissue autophagy-related proteins LC3II, P62, beclinl, P-AMPK/AMPK, P- mTOR/mTOR and apoptosis protein P53.Results Water maze test showed that Rgl and Hap significantly improved the learning and memory abilities of brain-ag¬ing mice.HE and Nissl staining showed that Rgl and Rap decreased necrotic cells and increased the number of Nissl bodies in the hippocampus of brain-aging mice.Immunohistochemistry staining showed that Rgl and Rap decreased the expression of neuronal autoph- agv protein P62 in hippocampus and increased the ex-pression of ATG5 and ULK1.Rgl and Rap decreased the activity of AhcE in brain-aging mice.Western blot showed that Rgl and Rap increased autophagy-related proteins LC3II, Beclinl , P-AMPK/AMPK, but de¬creased the expression of P-mTOR/mTOR, P62, P53.Conclusions Ginsenoside Rgl can effectively antago¬nize the aging effect of D-gal on mouse brain.The pos¬sible mechanism is related to the regulation of autoph- agv by Rgl through AMPK/mTOR signaling pathway.

OBJECTIVE: To investigate the clinical characteristics and risk factors of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). METHODS: Clinical data from 270 SAA patients with allo-HSCT were retrospectively analyzed, including 108 sib congruence patients and 162 substitute donors (68 unrelated donor congruence patients and 94 related haploid patients). Different pretreatment schemes were selected for different transplantation modes. The HLA-identical sibling and haploid grafts were all bone marrow and peripheral blood stem cells, and the grafts from unrelated donors were peripheral blood stem cells. After granulocyte implantation, blood CMV-DNA was regularly monitored. Flow cytometry was also used to determine the absolute number of CD3 RESULTS: CMV infection occurred in 229 of 270 patients with an incidence of 84.8%. Among them, 18 patients developed giant cell disease. Univariate analysis showed that alternative donors (unrelated total and haploid donors), mycophenolate mofetil and acute graft-versus-host disease were statistically significantly associated with CMV infection (P<0.05). Multivariate analysis showed that alternative donors were associated with CMV infection. The recovery of CD3 CONCLUSION After allo-HSCT, substitute donors are more easily to develop CMV infection than full-sibling donors, and the reconstruction of immune function is delayed after transplantation.
Anemia, Aplastic ; Cytomegalovirus Infections ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies

Objective: To analyze the phenotype and genotype of a Chinese pedigree with inherited dysfibrinogenaemia and investigate the molecular mechanism of the disease. Methods: Venous blood samples were collected from all family members, and routine coagulation tests were conducted. Functional fibrinogen in venous blood samples was measured by Clauss method, and the antigen level of fibrinogen in plasma was measured by immunoturbidimetry assay. All the exons and exon-intron boundaries of the three fibrinogen genes were analyzed by direct sequencing. Fibrinogen electrophoresis, fibrinogen clottability measurement, fibrin polymerisation measurement and electron microscopy scanning were also used to investigate the molecular characteristics and pathogenesis. Results: The proband had normal activated partial thromboplastin time, prothrombin time and plasma fibrinogen antigen, but prolonged thrombin time, prolonged reptilase time and reduced fibrinogen activity level, which were also found in his father. The sequencing results of the proband revealed heterozygous A1211G in the exon 2 of FGA gene originating from his father, which caused Arg19Gly missense mutation. The western-blot results showed that no abnormal bands of plasma fibrinogen were found in the proband and his father. Both thrombin-induced fibrin polymerisation and reptilase induced fibrin polymerisation were significantly impaired compared to normal control. Fibrinogen clottability measurement showed that only about 20.8% molecules of plasma fibrinogen in the proband were involved in the clot formation. Scanning electron microscopy revealed that the proband′s average fibre diameters were found to be significantly thicker than that of the control(P＜0.001), and the density was smaller than that of normal control. Conclusion The Arg19Gly mutation should be responsible for the proband′s dysfibrinogenaemia and the relevant clinical symptoms.

Hepatocellular carcinoma(HCC) is the most common malignancy in the world. Although there is progress in HCC diagnosis and treatment, it is still the third leading cause of cancer death worldwide because it is not easily diagnosed early and the disease progresses quickly. China is a high-risk area for HCC, and the number of cases is high and on the rise. Its prevention and treatment is a pressing problem. At present, western medicine is still unclear about the complex pathogenesis and clinical treatment of HCC. There are still many shortcomings and huge challenges. Traditional Chinese medicine(TCM) has its unique advantages in the treatment of HCC. With an overall concept, it has unique therapeutic effect and fewer side effect on HCC,it can not only inhibit tumor growth, but also alleviate patients' clinical symptoms and improve their quality of life. Therefore, the study of the effect of TCM in treating HCC has attracted the attention from many clinicians and researchers. However, the chemical composition of TCM formula is complex, with many targets and huge network of pharmacodynamic mechanisms, which greatly limits the research on the development of clinical drugs for the Chinese medicine formula. In recent years, there have been achievements in the studies of anti-hepatocarcinoma efficacy and mechanism of action of Chinese medicine compound, which mainly focused on the compound's effect in inhibiting the proliferation of hepatocarcinoma cells, blocking cell cycle and inducing apoptosis and autophagy, inhibiting liver cancer cell invasion and metastasis, regulating the immune function, synergism and attenuation, and reversing the drug resistance. In this paper, domestic and foreign literatures on the above-mentioned pharmacodynamics and mechanism of anti-liver cancer of TCM compound were studied, analyzed, summarized and summarized. This paper briefly reviews the research progress of its anti-hepatocarcinoma mechanism, and provides scientific ideas and evidence for the future study of the anti-hepatocarcinoma mechanism of TCM compound and its rational clinical application.

Objective: To observe the effect of modified Chaihu Shugantang on the expression of miRNA-204 in hippocampus of epileptic mice, and to explore its mechanism of neuroprotection. Method: The sixty mice were randomly divided into 6 groups:normal group, model group (pilocarpine 180 mg·kg^-1), and modified Chaihu Shugantang group (7 g·kg^-1·d^-1), modified Chaihu Shugantang+miRNA-204 mimic group (7 g·kg^-1·d^-1+ 2 μL), modified Chaihu Shugantang+miRNA-204 inhibitor group (7 g·kg^-1·d^-1+2 μL), carbamazepine group (30 mg·kg^-1·d^-1),each was given intragastric administration for 2 weeks,using pilocarpine to cause epilepsy in mice, respectively, add flavor to Bupleurum after intragastric administration, inhibition and overexpression of miRNA-204, the mice were sacrificed and their hippocampus tissues were harvested.The indicators of each group were observed, Real-time quantitative PCR detecting system (Real-time PCR) was used to detect mouse hippocampal miRNA-204 expression, Western blot analysis of autophagy-related protein microtubule-associated protein light chain 3 (LC3), autophagy-associated marker protein 7 (ATG7) expression, hematoxylin pathological condition of hippocampus in each group was observed by hematoxylin-eosin(HE)staining.The autophagy of hippocampus in each group was observed by transmission electron microscopy. Result: Compared with normal group, the expression of miRNA-204 was significantly decreased in model group (P<0.01), the pathological changes in the hippocampal C1 area were the most obvious, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was increased (P<0.01), and the autophagy was small. Compared with model group, the expression of miRNA-204 in the hippocampus of the modified Chaihu Shugantang group was increased (P<0.05), the pathological changes in the hippocampal C1 area were alleviated, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was decreased (P<0.05), and the autophagy was small. The number of body decreased,the expression of miRNA-204 in hippocampus of modified Chaihu Shugantang+miRNA-204 mimic group was significantly increased (P<0.01), the pathological changes in hippocampal C1 area were the lightest, and the expression of ATG7, LC3Ⅱ/LC3I was decreased (P<0.01), the number of autophagosomes was the least.Compared with modified Chaihu Shugantang group, the above-mentioned indicators of modified Chaihu Shugantang+miRNA-204 inhibitor group had the same change trend and the change range decreased (P<0.05). Conclusion: Modified Chaihu Shugantang can improve the pathological changes of hippocampus in mice with epilepsy and play a neuroprotective role. The mechanism may be to increase the expression of miRNA-204 in hippocampus of mice with epilepsy, inhibit excessive autophagy of neurons and reduce apoptosis.

BackgroundNanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.

MethodsWe synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.

ResultsWe demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.

ConclusionThe use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

Background: Accumulating documents have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis. As an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1) has been identified to be involved in the progression of many types of cancers. However, the biological function of NEAT1 in cervical cancer is not fully investigated. The aim of this study was to disclose the specific biological function of lncRNA NEAT1 in cervical cancer progression. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to identify the expression of lncRNA NEAT1 in the cervical cancer tissues and cell lines. All cervical cancer samples used in this study were collected from the Affiliated Suzhou Hospital of Nanjing Medical University between September 2012 and September 2017. The correlation between NEAT1 expression and the overall survival rate of cervical cancer patients was analyzed by Kaplan-Meier analysis. The effects of NEAT1 knockdown or overexpression on cell proliferation were tested by performing MTT assays and colony formation assays. Transwell assays were conducted to detect the migratory ability of cervical cancer cells, in which NEAT1 was silenced or overexpressed. Western blotting was utilized to validate whether NEAT1 promotes cervical cancer progression through activating PI3K-Akt signaling pathway. Results: High expression of NEAT1 predicted poor prognosis of cervical cancer patients (χ = 0.735, P = 0.005). Knockdown of NEAT1 decreased the number of colonies in CaSki cell from 136.667 ± 13.503 to 71.667 ± 7.506 (t = -18.76, P = 0.003) and decreased the number of colonies in HeLa cell from 128.667 ± 13.317 to 65.667 ± 7.024 (t = -5.54, P = 0.031). However, overexpression of NEAT1 increased the number of colonies in SiHa cell from 84.667 ± 12.014 to 150.667 ± 18.037 (t = 7.27, P = 0.018). Knockdown of NEAT1 decreased the migratory number of CaSki cell from 100.333 ± 9.866 to 58.333 ± 5.859 (t = -8.08, P = 0.015) and reduced the migratory number in HeLa cell from 123.667 ± 12.097 to 67.667 ± 7.095 (t = -6.03, P = 0.026). Overexpression of NEAT1 increased the migratory number of SiHa cell from 127.333 ± 16.042 to 231.333 ± 31.786 (t = 4.92, P = 0.039). Conclusion NEAT1 may exert oncogenic function in cervical cancer and serve as a novel therapeutic target for cervical cancer.
Cell Line, Tumor ; Cell Proliferation ; Female ; HeLa Cells ; Humans ; Middle Aged ; Phosphatidylinositol 3-Kinases ; physiology ; RNA, Long Noncoding ; physiology ; Uterine Cervical Neoplasms ; genetics

Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PS1/tau triple-transgenic AD mice (3×Tg-AD mice) and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expression levels of hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.
Alzheimer Disease ; metabolism ; pathology ; psychology ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Disease Models, Animal ; Female ; Hippocampus ; metabolism ; pathology ; Humans ; Inflammation ; metabolism ; pathology ; psychology ; Male ; Maze Learning ; physiology ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurofibrillary Tangles ; metabolism ; pathology ; Plaque, Amyloid ; metabolism ; pathology ; psychology ; Presenilin-1 ; genetics ; metabolism ; Sex Characteristics ; Spatial Memory ; physiology ; p38 Mitogen-Activated Protein Kinases ; metabolism ; tau Proteins ; genetics ; metabolism