Abstract:Parkinson disease (PD) combined with cognitive impairment has attracted much attention due to its high disability. A large number of studies have found that cerebral small vessel disease is closely related to the pathology and pathogenesis of PD combined with cognitive impairment. This article reviews the advances in the relative research of cognitive impairment and cerebral small vessel disease in patients with PD.

Abstract:Gut microbiota interacts with the central neural system. Gut microbiota can regulate neural system, endocrine system, and immune system, etc., thus leading to the progress of neurodegenerative diseases. This paper reviews the research history of the gut microbiota, and focuses on its current progress in neurodegenerative diseases including Alzheimer's disease, Parkinson disease and amyotrophic lateral sclerosis. Accumulating evidence indicates that the gut microbial homeostasis may be destroyed in neurodegenerative diseases. Therefore, the maintenance of normal gut microbial homeostasis, such as by antibiotic and probiotic therapy and fecal transplantation, will provide new ways and ideas for the prevention and treatment of these kind of diseases.

Abstract:Ischemic stroke is one of the leading causes of mortality and disability worldwide. Scientists have been trying to clarify the cellular and molecular pathophysiological processes. Long non-coding RNAs (lncRNAs) play an important role in a lot of diseases. Recent studies have found that there were a bulk of differentially expressed lncRNAs in both ischemic stroke patients and animal models. They participated in regulating cell apoptosis, angiogenesis, inflammation, and cell death. Those investigations may help to elucidate the mechanisms and functions of lncRNAs in ischemic stroke, which may provide new strategies for seeking new biomarkers and therapeutic targets of ischemic stroke.

Abstract:Gilles de la Tourette syndrome (TS) is a kind of neurodevelopmental disorder in childhood, which brings a lot of inconveniences to children's study and life, and seriously affects their physical and mental health. Some children have difficulties integrating into the society when they grow up. The etiology and pathogenesis of TS are still not clear. At present, the widely recognized mechanism is that TS has a close relationship with central neurotransmitters. This paper reviews the relationship between TS and neurotransmitters.

Abstract:Objective:　To explore the effects of azure B on metabolism of amyloid precursor protein (APP) and generation of amyloid-beta (Aβ) protein. Methods:　Neuron-2a cells that stably expressed APP695 gene (N2a-APP695) was treated with azure B.Levels of APP, soluble APPα (sAPPα) and β-site APP cleaving enzyme 1 (BACE1) were measured by Western bolt. Aβ levels were measured by ELISA. The BACE1 enzyme inhibition was determined by using BACE1 activity assay kit. Data were analyzed by t test. Results:　①Azure B was not able to influence the cell viability of N2a-APP695 cells with final concentration of 5, 10, 15 and 20 μmol/L.②According to ELISA results, azure B was able to decrease levels of Aβ_1-40 (P=0.002) and Aβ_1-42 (P=0.036). ③Western blot demonstrated that azure B was able to reduce levels of full length APP (P=0.018) and sAPPα (P=0.006), but not influence the protein level of BACE1 (P>0.05).④BACE1 activity assaying results showed that the activity of the BACE1 enzyme was significantly inhibited by azure B, with inhibition rate of 66.0% (P=0.000). Conclusion:　Azure B inhibits the generation of Aβ by inhibiting the expression of APP and the activity of BACE1.

Abstract:In the pathogenesis of ischemic stroke, due to the breakdown of blood-brain barrier structures such as endothelial cells, reperfusion injury, and coagulation dysfunction after thrombolytic therapy, etc., the restored blood flow enters the brain tissue from the damaged blood vessels, which is called hemorrhagic transformation (HT). Severe HT is one of the causes of death in patients. Researches find that HT may be related to many factors, such as venerable age, diabetes, and the severity of the patient's condition. It will be helpful for the prevention and treatment of clinical HT whether the probability of HT can be determined quantitatively by biological markers and reduced by management. Therefore, this paper reviews the advances in this area.

Abstract:Oxidative reaction, inflammatory action, and mitochondrial dysfunction caused by erythrocyte lysates will lead to secondary brain injury within hours to days of cerebral hemorrhage. It has been found recently that peroxisome proliferator-activated receptorgamma (PPAR-γ) plays multiple roles in endogenous hematoma clearance systems. When PPAR-γ is activated, it not only plays a role in anti-inflammatory and anti-oxidation, but also mediates the role of phagocytic cells in clearing hematoma to protect neurons. Therefore, PPAR-γ may be a potential target for the treatment of secondary brain injury after intracerebral hemorrhage.

Abstract:Objective:　To identify the expression of RNA hsa_circ_0066336 (circFLNB) in bone marrow-derived cells, and to analyze its potential function. Methods:　Bone marrow-derived cells THP-1 and Jurket were selected as model cells. Divergent primers were designed, and differences of circRNA expression in two model cells were analyzed. T-A cloning was used to construct plasmids for comparing. Then Arraystar software was used to predict the target miRNA of hsa_circ_0066336. The target miRNA was extracted and reverse transcribed from THP-1, and then was detected by Real-time PCR. Results:　①CircFLNB was successfully amplified in THP-1 and Jurket cells, and statistical analysis showed that their expression was not significantly different in two model cells (P=0.105). ②The plasmid containing hsa_circ_0066336 was cloned, and a back-splice junction was found after comparing two sequences.③Five target miRNAs of hsa_circ_0066336 were predicted by Arraystar software and corresponding expressions were detected. Conclusion:　CircFLNB is a circular RNA expressed in bone marrow derived cells and it is suggested that circFLNB may involve in the development of various diseases by comprehending its downstream miRNA function.

Abstract:Objective:　To uncover the key genes and biological process of Alzheimer's disease by RNA sequencing data analysis. Methods:　Initially, GSE125050 RNA sequencing data was obtained from the GEO database. After quality control and filtration, data were conducted genes differentially expression analysis by edgeR. Gene enrichment analysis of GO and KEGG were performed on differentially expression genes (DEGs) by Matescape database. Genes set enrichment analyses (GSEA) were performed on the biologically significant genes set. Protein-protein interaction network was constructed using neuron DEGs, to identify hub genes in protein level. Results:　The number of differentially expression genes from neuron, myeloid, astrocyte, endothelial samples was 561, 491, 223, 3 072, respectively. Neuron's DEGs were significantly correlated with G alpha (s) signaling events and keratinization. Endothelial DEGs were significantly enriched at olfactory signaling pathway. GSEA showed neuron differential expression was related to activation of immune response. TLR8, FCGR2A, CD19, LCK, CD2, CD40, ITGAM were screened out by PPI network as hub genes. Conclusion:　TLR8, FCGR2A, CD19, LCK, CD2, CD40, ITGAM may play a significant role in neuroinflammation in AD occurrence.

Abstract:Objective:　To investigate the nerve injury mechanism of c-Jun N-terminal kinase (JNK) in in vitro rat brain slices after oxygen glucose deprivation (OGD). Methods:　The hippocampal slices of sprague dawley (SD) rats (7 days after birth) were prepared. Rats were divided into the normal control group, the model group and the inhibitor group. Brain slices in the normal group were not treated with OGD, in the model group were treated with OGD for 30 minutes, and in the inhibitor group were treated with OGD for 30 minutes and treated with 10 μmol/L SP600125.Levels of phosphorylated JNK (p-JNK) of hippocampal slices in different groups were detected by Western blot, potential changes of neurons of CA1 region in different groups were detected by whole cell patch clamp in current clamp mode, and the lactate dehydrogenase (LDH) releasing of hippocampal slices in different groups were also detected. Results:　After 30 minutes of OGD, the phosphorylation level of JNK was significantly increased. Meanwhile, the potential absolute value of neurons in "resting state" was decreased, while the releasing level of LDH was increased. In addition, SP600125 was able to inhibit the phosphorylation of JNK, so as to recover the potential absolute value of neurons and inhibit the releasing of LDH (P<0.05). Conclusion:　Inhibiting the over-activation of JNK signaling pathway can alleviate the neurological damage after OGD in rat hippocampal slices, and its mechanism may relate to the regulation of neuronal electrical state in "resting state" and LDH releasing.

Abstract:Objective:　To explore the correlation between the apolipoprotein E (APOE) gene polymorphisms and the incidence of hemifacial spasm. Methods:　The information of 94 hemifacial spasm cases (hemifacial spasm group) diagnosed in The First Affiliated Hospital of Chongqing Medical University and 73 normal subjects (control group) was collected for this research. And the APOE genotype was determined by means of cleaved amplification polymorphism sequence-tagged sites (CAPs). Then we obtained the gene frequency of APOEε2, APOEε3 and APOEε4, and compared the distribution of allele between the hemifacial spasm group and the control group. Results:　The rate of APOEε4 allele gene in hemifacial spasm group was 15.43%, which was significantly higher than that in control group (6.85%). And the carriers of APOEε4 allele gene accounted for 29.79% in the hemifacial spasm group, which was also significantly greater than that in control group (13.70%). There were significant differences between the two groups (P=0.014). Conclusion:　The morbidity of hemifacial spasm is associated with the APOE gene polymorphisms, and the carriers of APOEε4 allele gene may be more likely to suffer from the hemifacial spasm.

Abstract:Objective:　To assess the efficacy of transcranial sonography (TCS) on substantia nigra in Parkinson disease (PD) on the basis of Meta analysis. Methods:　Studies about TCS from January 2010 to November 2019 in databases of PubMed, Embase, Cochrane library, CNKI, VIP and CBM were searched and collected. Two evaluators independently screened the literature, evaluated the quality of the literature and extracted relevant information according to inclusion and exclusion criteria. Meta-DiSc1.4 software was used to perform the Meta analysis, corresponding effect model was selected according to the heterogeneity results, effect size and 95% confidence interval (95%CI) were calculated, the receiver operator characteristic (ROC) curve was drawn, area under the curve (AUC) as well as Q value was calculated and Deek's funnel plot was drawn by adopting Stata 12.0 software to evaluate and publish bias. Results:　A total of 753 literatures were retrieved and 28 literatures were finally included. Meta analysis results showed that the combined sensitivity of TCS in diagnosing PD was 0.82 (95%CI=0.80-0.83), the combined specificity was 0.90 (95%CI=0.88-0.91), the diagnostic odds ratio was 42.84 (95%CI=28.37-64.68), the positive likelihood radio was 7.46 (95%CI=6.11-9.11), the negative likelihood radio was 0.19 (95%CI=0.15-0.25), and SROC AUC and Q index were 0.947 0 and 0.886 5, respectively. Conclusion:　As a new auxiliary examination method for neurological diseases, TCS has a high diagnostic value in the diagnosis of PD, non-invasive, radiation-free, economical and easy to operate, which can be promoted in the clinical as an early screening and auxiliary diagnostic tool for PD.

Abstract:Objective:　To investigate the clinical efficacy of small bone flap craniotomy for hematoma elimination in the treatment of hypertensive cerebellar hemorrhage. Methods:　The clinical data of 23 patients with hypertensive cerebellar hemorrhage treated with small bone flap craniotomy for hematoma elimination was retrospectively analyzed. CT scan were reexamined after operation based on the individual condition and GOS (Glasgow outcome scale) scores of 1 month and 3 months follow-up after operation. Results:　CT scan was performed in all patients within 24 hours after operation. Among them, 22 cases of hematoma were completely eliminated and 1 case was mostly eliminated (residual volume of hematoma<10%). One month after operation, 20 cases had GOS score of 5 points, 3 cases had 4 points. Routine follow-up of 3 months after operation, 22 cases had GOS score 5 points and 1 case had 4 points. Conclusion:　The "small bone flap hematoma craniotomy for hematoma elimination" in the treatment of hypertensive cerebellar hemorrhage has the advantages of less trauma, short operation time, less complications, quick recovery and optimistic prognosis, which is worthy of promotion and application in hospitals with mature microscopic technology.

Abstract:Objective:　To investigate the role of A1 adenosine receptor (A1AR) in secondary brain injury (SBI) induced by intracranial hemorrhage (ICH). Methods:　Thirty adult male SD rats were randomized into sham operation group, ICH group, agonist group [A1 adenosine receptor agonist N (6) -cyclohexylflavin, R-PIA] and antagonist group (A1 adenosine receptor antagonist 8-phenyl-1, 3-dipropylxanthine, 8-PT), with 6 rats in each group. A collagenase-induced ICH model was established. The agonists and antagonists were administered 30 minutes before modeling and examinations were performed 48 hours later. The expressions of A1AR, active Caspase-3, albumin, B cell lymphoma 2 (Bcl-2) and Bax were detected by Western blot. The apoptosis of neurons was observed by TdT-mediated dUTP nick-end labeling (TUNEL). The degree of brain edema was evaluated by wet/dry ratio. Results:　The expression of A1AR in agonist group was significantly up-regulated (P=0.000), while that in antagonist group was down-regulated. In agonist group, apoptosis decreased (P=0.003), and the levels of active Caspase-3 and albumin decreased (t=4.649, P=0.043; t=24.89, P=0.001). In the antagonist group, apoptosis increased, and the levels of active Caspase-3 and albumin were up-regulated (t=12.49, P=0.006; t=8.501, P=0.013). In agonist group, Bcl-2 expression increased (t=14.13, P=0.005), Bax expression decreased, and the degree of brain edema decreased (P=0.007). Conclusion:　Activation of A1AR can increase the expression of Bcl-2, relieve brain edema, reduce nerve cell apoptosis and inhibit secondary brain injury.

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Abstract:Objective:　To study the infiltration patterns of immune cells in cutaneous melanoma and to explore the relationship between immune cells infiltration and clinical prognosis. Methods:　Transcripts and related clinical data of cutaneous melanoma were downloaded from the cancer genome atlas (TCGA) database. The proportion of 22 kinds of immune cells were calculated by deconvolution method with Cibersort software. The correlation between immune cells proportion and gender was calculated by R programming language, and K-M survival analysis with log-rank method was used to determine the correlation between each kind of immune cells and overall survival (OS). Results:　A total of 472 gene transcripts were obtained from the TCGA database, including 470 cases of cutaneous melanoma and 2 cases of normal tissues. Each sample detected 60, 483 genetic loci and extracted 19, 658 mRNAs. After data correction, the proportion of 22 kinds of immune cells was obtained by deconvolution method with Cibersort software. Totally 219 cases of cutaneous melanoma and 1 case of normal skin tissue were obtained by screening samples with the criteria P<0.05. M0 macrophages, CD8⁺T cells, and M2 macrophages were the types of immune cells with higher levels of infiltration in melanoma tissues. The strongly correlated immune cells included CD8⁺T cells and M0 macrophages (-0.62), and inactivated CD4⁺T cells and CD8⁺T cells (-0.53).K-M survival analysis showed that patients with the higher proportion of inactivated mast cells (P=0.015) and inactivated NK cells (P=0.025) had worse prognosis, and patients with the higher proportion of γδT cells (P=0.043) had better prognosis. The proportion of inactive mast cells in female with melanoma was less than that in male (P=0.028). Conclusion:　There are differences in the composition of infiltrated immune cells in cutaneous melanoma. These cells are likely to be important determinants of prognosis, which helps us develop effective immunotherapy.

Abstract:Objective:　To investigate the clinical efficacy and adverse reactions of gefitinib combined with Endostar in the first-line treatment of EGFR mutation positive advanced lung adenocarcinoma. Methods:　Sixty patients with lung adenocarcinoma with EGFR exon 19-21 mutation inoperability or postoperative recurrence and metastasis admitted to the Chengdu Fifth People's Hospital from January 2016 to January 2019 were randomized into control group and study group, with 30 cases in each group. Patients in control group were treated with gefitinib alone, while patients in study group were treated with Endostar on the basis of gefitinib, with 21 days as a cycle. Objective response rate (ORR), pain response, tumor markers, adverse drug reactions, progression free survival (PFS) and overall survival (OS) were compared between the two groups. Results:　The ORR of the study group was significantly higher than that of the control group (83.33% vs.50.00%, P<0.05). The pain relief degree of the study group was significantly better than that of the control group (P<0.05). The level of tumor markers (serum CEA, CYFRA21-1 and CA199) in the two groups decreased after the treatment, and the study group dropped more significantly than the control group (P<0.05). There were no gradeⅣadverse reactions in both groups. The rash in the study group was less than that in the control group, but there were individual cases of mild bleeding. The mPFS of the control group was 9.18 months (95%CI=7.80-10.56), and the mPFS of the study group was 15.23 months (95%CI=13.07-17.39), with significant differences (P<0.05). The mOS of the control group was 17.98 months (95%CI=14.40-21.57) and that of the study group was 25.95 months (95%CI=20.09-26.17), with significant differences (P<0.05).Further subgroup analysis showed that PFS and OS in the study group were significantly longer than those in the control group, regardless of the mutation in exon 19 or exon 21. Conclusion:　Gefitinib combined with Endostar in the first-line treatment of EGFR mutation positive advanced lung adenocarcinoma can effectively improve the clinical efficacy, prolong the survival period of patients, reduce the level of tumor markers, and does not increase the adverse drug reaction rate, with high security, which is worthy of promotion in the first-line treatment of advanced non-small cell lung cancer.

Abstract:Objective:　To analyze the influencing factor of catheter placement length in totally implantable central venous port (TICVP) via right internal jugular vein, and to establish a regression equation based on the right third intercostal space as an anatomical landmark to measure the length of the catheter. Methods:　A total of 190 patients with right internal jugular vein TICVP in First Affiliated Hospital of Xi'an Jiaotong University from September 2017 to July 2018 were collected. Intraoperative fluoroscopy was used to determine the length of the catheter and the distance from the puncture site to the right third intercostal space (SK-ICS) was recorded. Pearson correlation analysis was used to analyze the correlation between the actual catheter length and the patients'age, height, weight, BMI and SK-ICS. The regression equation was established by multiple linear regression analysis and other three commonly used formulas were used to compare. Results:　Catheter length had a positive correlation with patients'height, weight and SK-ICS (P<0.05), while had a negative correlation with BMI (P<0.05). The regression equation of L=1.01×SK-ICS+0.151 was obtained through multiple linear regression analysis. The estimated value of the equation had no significant difference compared with the actual length (P>0.05), while the other three formulas were longer than the actual value. The absolute error and percentage value of the regression equation were relatively lower, with higher accuracy for predicting catheter length. Conclusion:　The regression equation established by the surface anatomical landmark has certain clinical guiding values and promotion significance for the estimation of catheter length.

Abstract:Objective:　To investigate the pathogenesis, clinical features, and surgical treatment of intravenous leiomyomatosis with intracardiac extension, and to improve the understanding of this disease. Methods:　We retrospectively analyzed the clinical data, diagnosis and treatment of 3 patients with intravenous leiomyomatosis with intracardiac extension in The First Hospital of Lanzhou University, and reviewed relevant literature. Results:　All the 3 patients were successfully treated with surgery. Among them, 2 patients underwent thoracoabdominal incision with one-stop surgery of "uterine, accessory, pelvic mass resection and removal of intracardiac and inferior vena cava tumors". Another patient's surgery was performed in two phases. During the first phase, "right atrial mass resection+tricuspid valvuloplasty" was performed firstly. After 1 week, we performed a second surgery "full hysterectomy+bilateral adnexectomy+removal of inferior vena cava tumor+right ureteral stent implantation". All 3 patients were successfully operated and recovered and discharged after the surgery. Conclusion:　Intravenous leiomyomatosis with intracardiac extension is rarely seen in clinic. Thorough resection of the tumor is the key to the treatment of this disease. The surgery requires multiple disciplines to be combined, which can be completed in one-phase one-stop, or can be completed in stages by stages. Two kinds of surgical methods both can achieve satisfactory therapeutic effect in clinic.

Abstract:Diabetes mellitus caused by immune checkpoint inhibitors is a rare type of immune-related adverse events in endocrinology. However, this type of diabetes often begins with diabetic ketoacidosis, which is more dangerous. This article reviews the literatures on immune checkpoint inhibitors-induced diabetes mellitus and its clinical manifestations and diagnosis and treatment strategies.

Abstract:This paper focuses on the research progress of exosomes, including the theory of exosome composition, secretion and uptake, the regulation role of exosomes in bone metabolism, the associated action of exosome in the pathogenesis, diagnosis and treatment of bone and joint diseases, and the application of exosome in the field of regenerative medicine, so as to further explore the potential research and application space of exosomes.

Abstract:Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus, and it's also a common type of secondary chronic kidney disease (CKD) as well as the main cause of end stage renal failure. The specific pathogenesis of DKD is not well understood yet, which is related to many factors, and current research indicates that inflammation plays an important role in the development and progression of DKD. This review summarizes the role of relevant inflammatory molecules and signaling pathways in the progression of DKD. At the same time, we also have reviewed the beneficial effects of several drugs targeting cytokines, chemokines, transcription factors, kinases and molecules that promote the resolution of inflammation as well as several anti-inflammatory compounds on DKD. Therefore, the use of targeted drugs against these inflammatory factors, inflammatory signaling pathways and their downstream products as well as molecules that promote the resolution of inflammation to control inflammation may become a new approach and measure for DKD treatment in the future.

Abstract:Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease and most patients have symptoms of thyroid dysfunction, without unclear specific pathogenesis. Currently, it is generally believed that TAO is associated with Graves'disease and is a cross reaction between anti-thyroid antibodies and ocular autoantigen. TAO mainly damages the extraocular muscle, orbital adipose tissue and intraorbital connective tissue, presenting as orbital glycosaminoglycan aggregation, orbital fibrosis, adipose tissue hyperplasia, orbital tissue remodeling and exophthalmic protrusion. TAO can be caused by many factors, including genetic factors, immune factors and other factors. This review aimed to introduce the immune-related pathogenesis of TAO and its influencing factors.

Abstract:Liver cancer is one of the malignant tumors with high incidence and extremely poor prognosis in China. Current treatments such as surgery, radiotherapy, and chemotherapy have been proved to be limited effects. It is very necessary to develop new therapeutic methods. Immunotherapy is one of the potentially effective treatments. Programmed cell death receptor-1 (PD-1) is an important immune checkpoint, which is mainly expressed on activated T lymphocytes, B lymphocytes and NK cells, and has an immunosuppressive effect. Multiple tumors highly express programmed cell death-ligand 1 (PD-L1), and PD-L1 binds to PD-1 on the surface of T cells and other cells, exerting negative immune regulation, leading to inactivation of T lymphocytes and thus tumor immune escape. A couple of studies have found that blockage of PD-1 can rebuild the immune surveillance function of T lymphocytes and prolong the overall survival of patients with liver cancer and other tumors. In this article, we have reviewed the advances of PD-1 targeted therapy for liver cancer. The key issue that needs to be solved is how to maximize the response rate of antibodies against immune checkpoints and meanwhile reduce the incidence of immune-related adverse events through combination therapy and other methods.