Abstract:With the increasing aging of the population， the number of patients with Alzheimer disease （AD） is growing year by year. Early screening， early detection and early intervention have become the strategy and consensus for the prevention and treatment of AD， so the research on noninvasive peripheral biomarkers is particularly important. This article mainly reviews and summarizes the research progress of domestic scholars on urine biomarkers of AD in the past decade. Most of the research findings in the references come from the detection and observation of human urine samples. It suggests that we should pay attention to the exploration and application of noninvasive peripheral biomarkers， which provide a new perspective as well as new ideas for the early diagnosis and early intervention of diseases.

Abstract:Objective To analyze the quality of life among children with tic disorders and the influencing factors. Methods A total of 150 children and adolescents aged from 4 to 15 years were enrolled in tic disorders group， who were first diagnosed with tic disorders in the Pediatric Outpatient Department of Renmin Hospital of Wuhan University from June 2019 to December 2020. Another 150 age- and gender-matched healthy children who underwent health examinations during the same period in the Child Healthcare Department of the same hospital were randomly selected as the control group. The Yale Comprehensive Tic Severity Scale （YGTSS） and the Achenbach Child Behavior Scale （CBCL） were used respectively to assess the tic disorders and behavioral status of all research subjects. The Pediatric Quality of Life Inventory 4.0， Generic Core Scales of the Chinese version （PedsQL） was used to assess the quality of life of the two groups. The generalized linear model was used to analyze the influencing factors of PedsQL total score and each part score in children with tic disorder. Results The subscale score of social-psychological domain of PedsQL was lower than the subscale score of physical domain among children with tic disorders. The subscale score of school performance of PedsQL in tic disorders group was significantly lower than that in control group （P＜ 0.05）. The results of the generalized linear models showed that the subscale score of physical functioning （physical domain） in tic disorders cases was positively correlated with democratic parenting pattern （β=0.102， 95%CI=0.009-0.196） and normal behavior （β=0.094， 95%CI=0.020-0.168） （P ＜ 0.05）. The subscale score of emotional functioning was positively correlated with personal physical fitness （β=0.128， 95%CI=0.006-0.250）， the education level of the mother is high school （β=0.118， 95%CI=0.018-0.217） or middle school and below （β=0.137， 95%CI=0.038-0.236）， and normal behavior （β=0.170， 95%CI=0.087-0.253） （P＜ 0.05）. The subscale scores of social functioning and social-psychological domain were positively correlated with normal behavior （β=0.106， 0.154；95%CI=0.039- 0.172， 0.091-0.217） （P ＜ 0.05）. The subscale scores of school performance was negatively correlated with the education level of the mother is middle school and below （β=-0.172，95%CI=-0.303- -0.041）， and positively correlated with normal behavior （β=0.246， 95%CI=0.147-0.344） （P＜ 0.05）. PedsQL total score was positively correlated with mild tic disorders （β=0.062， 95%CI=0.006-0.119） and normal behavior （β=0.135， 95%CI=0.077-0.192） （P ＜ 0.05）. Conclusions The school performance of children with tic disorders is worse than that of normal healthy children. The quality of life among children with tic disorders is significantly related to their personal physical fitness， parenting pattern， parental education levels and comorbid behavioral problems

Abstract:Objective To discuss the possibility of the minimally invasive design of far lateral approach exposing foramina magnum based on virtual reality anatomic model. Methods Image data of CT and MRI scans performed to fifteen adult cadaver heads （30 specimens） was inputted into Vitrea virtual reality system to establish three-dimensional anatomy model. Osseous landmark points on the calvaria and skull base were selected to outline cylinder simulating far lateral exposing foramina magnum. Minimally invasive design was made by reduce the size of cylinder. Anatomic exposures before and after design were observed and compared. Results Surgical routes before and after minimally invasive design avoided sigmoid sinus， jugular bulb and cerebellum. The route before minimally invasive design involved medullar with volume of （143.25±10.15） mm3 . However， the route following design avoid medullar. Comparison showed that volumes of the route， osseous structure， cranial nerve and artery following minimally invasive design were less than those before design ［（2 052.70±115.84）mm3 vs （8 346.80±122.98）mm3 ，（1 345.40±92.82）mm3 vs （4 291.00±111.81）mm3 ， （1.78±0.10）mm3 vs （52.23±0.82）mm3 ，（4.12±0.11）mm3 vs （163.95±9.92）mm3 ］， with statistical significance （P ＜ 0.01）. Conclusions Under the determined direction， reduction of surgical route size can reduce the injury， meanwhile， ensure exposure of anterior edge of foramina magnum for far lateral approach.

Abstract:Objective To explore the risk factors of pain in patients with herpes zoster after acute stage （1 month after onset）. Methods The patients with herpes zoster who visited the Department of Dermatology Xuanwu Hospital of Capital Medical University from November 2020 to April 2021 were selected as the research objects. The general data of patients were recorded， and the scores of Visual Analogue Scale （VAS）， Generalized Anxiety Disorder （GAD-2）， Patient Health Questionaire-2 （PHQ-2） and Pittsburgh Sleep Quality Index （PSQI） were evaluated at the initial diagnosis （onset） and follow-up （1 month after onset）. Univariate analysis and dichotomous Logistic regression analysis were applied to explore the high-risk factors for the occurrence of post-acute pain. Results A total of 235 patients were enrolled， including 102 males and 133 females. The onset age was （52.59±16.30） years old. Pain was present in 29.8% （70/235） of patients 1 month after onset. Univariate analysis showed that onset age， chronic disease， VAS score at initial diagnosis， GAD-2 and PHQ-2 score at follow-up， and sleep disorder after onset were the influencing factors of post acute pain in patients with herpes zoster （P ＜ 0.05）. The binary Logistic regression analysis showed that onset age ≥ 50 years old （P=0.005， OR=3.919， 95%CI：1.520-10.106）， VAS score ≥ 4 points at the initial diagnosis （P=0.016， OR=3.735， 95%CI：1.277-10.929）， GAD-2 score after onset （P=0.001， OR=3.944， 95%CI：1.817-8.562）， and 1 score of sleep persistence after onset （P=0.008， OR=7.569， 95%CI：1.699-33.725） were the risk factors for pain after acute stage. Conclusions The risk factors of post-acute herpetic neuralgia in patients are age ≥ 50 years old，pain with moderate or above at the time of initial diagnosis， anxiety state after onset and poor sleep persistence. Clinical attention should be paid to the anxiety state and sleep status of patients with herpes zoster.

Abstract:Objective To investigate the clinical features and risk factors of depression in newly diagnosed untreated people with Parkinson disease （PD）. Methods The data of a total of 218 newly diagnosed untreated PD patients in dyskinesia outpatient of Neurology Department of Affiliated Nanjing Brain Hospital， Nanjing Medical University from October 2010 to December 2019 and 171 age- and gender-matched healthy controls were retrospectively collected. The Unified PD Rating Scale （UPDRS） Part Ⅱ， Ⅲ and Ⅴ were used to examine the motor symptoms of PD patients. The PD Sleep Scale （PDSS）， Montreal Cognitive Assessment Scale （MoCA） and Non-Motor Symptom Quest （NMSQ） were used to assess non-motor symptoms in PD patients. The degree of depression and anxiety in PD group and control group were evaluated using the 24-item Hamilton Depression Scale （HAMD） and Hamilton Anxiety Scale （HAMA）. The incidence rate and clinical data were compared between the PD and control groups. The clinical symptoms of PD patients with depression （dPD） and those without depression （n-dPD） were compared. Multivariate Logistic regression was used to analyze the risk factors of depression in newly diagnosed and untreated PD patients. Results The HAMD score of PD group was 8.0 （4.0，13.0）， and the incidence of dPD was 12.4% （27/218）， with 5 cases of mild depression， 18 cases of moderate depression， and 4 cases of severe depression. The HAMD score of control group was 2.0 （0，2.0）， and the rate of depressive episode was 6.4% （11/171）， with 5 cases of mild depression， 5 cases of moderate depression， and 1 case of severe depression. The differences in severity and incidence rate of depression between the two groups were statistically significant （P ＜ 0.05）. The total score of HAMD-24 and each factor score， HAMA score and NMSQ score in dPD group were higher than those in n-dPD group. The proportion of patients in early stage， with aberrant posture instability and gait difficulty （PIGD） subtype in dPD group was higher than that in n-dPD group. The scores of UPDRS-Part Ⅱ and PDSS in dPD group were lower than those in n-dPD group （P＜ 0.05）. High HAMA score （OR=1.167， 95%CI=1.077-1.265）， high NMSQ score （OR=1.235， 95%CI=1.052-1.449）， and PIGD subtype （OR=2.024， 95%CI=1.053-3.891） were the risk factors of dPD. High PDSS score was the protective factor of dPD （OR=0.971， 95%CI=0.945-0.997） （P ＜ 0.05）. Conclusions The depression of newly diagnosed PD patients was mainly moderate depression. PD patients with anxiety， more non-motor symptoms， poor sleep quality and PIGD subtype were more likely to suffer from depression.

Abstract:Objective To explore the influence of family and other factors on suicidal behavior of adolescent depression patients. Methods A cross-sectional survey was conducted on 126 adolescent depression patients hospitalized in the Department of Child and Adolescent Psychology of Jingmen NO.2 People's Hospital from June 2020 to December 2021. The patients were divided into suicide group （n=76） and non-suicide group （n=50） according to whether they had committed suicide in the past 6 months. The general information questionnaire， Patient Health Questionnaire-9 （PHQ-9）， Self-Rating Idea of Suicide Scale （SIOSS）， the Chinese version of Family Adaptability and Cohesion Scale， Second Edition （FACES Ⅱ -CV） were applied to compare general information， depression degree， suicidal ideation and family classification. Spearman was used to analyze the correlation between suicidal behavior and general data， PHQ-9， SIOSS， and FACES Ⅱ -CV scores. Binary Logistic regression model was used to analyze the influencing factors of suicidal behavior. Results The drinking rate and family history of mental illness in the suicide group ［40.8% （31/76）， 27.6% （21/76）］were significantly higher than those in the non-suicide group ［20.0% （10/50）， 12.0% （6/50）］， and the differences were statistically significant （P ＜ 0.05）. The scores of PHQ-9， SIOSS total score， despair and sleep factor in the suicide group were higher than those in the non-suicide group ［19.0 （15.0，21.8） vs 15.0 （10.8，19.0）； 15.0 （14.0，16.8） vs 13.0 （11.0，15.0）； 12.0 （10.3，12.0） vs 10.0 （7.8，12.0）； 3.0 （2.0， 3.0） vs 2.0 （1.0， 3.0）］， and the family cohesion score was lower than that in the non-suicide group ［50.5 （43.3， 57.0） vs 57.5 （48.8，65.5）］， and the differences between the two groups were statistically significant （P ＜ 0.05）. In the suicide group， the rate of extreme family ［67.1% （51/76）］ was significantly higher than that of the non-suicide group ［44.0% （22/50）］， and the difference between the two groups was statistically significant （P ＜ 0.05）. The suicidal behavior was negatively correlated with family intimacy （r=-0.224， P ＜ 0.05）， and positively correlated with PHQ-9 score， SIOSS total score， despair factor score， sleep factor score， drinking behavior， and having family history of mental illness （r=0.346， 0.373， 0.361， 0.324， 0.206， 0.217， 0.186； P ＜ 0.05）. Binary Logistic regression analysis showed that alcohol consumption （OR=3.066， 95%CI=1.184-7.941）， high family adaptability （OR=1.126， 95%CI=1.034-1.227）， high PHQ-9 score （OR=1.197， 95%CI=1.087-1.317） were the risk factors for suicidal behavior of adolescent depression patients （P＜ 0.05）， and high family intimacy was the protective factor for suicidal behavior （OR=0.878， 95%CI=0.813- 0.948）. Conclusions Adolescent depression patients have a higher incidence of suicidal behavior. Family classifications are more common in "rigid-loose" extreme families. Alcoholic behavior， severe depression， and poor family relationships are more likely to commit suicide.

Abstract:Objective To explore the role of T-lymphocyte subsets （CD3+ ， CD4+ ， CD8+ ， CD4+ / CD8+ ） in early recognition of neurosyphilis. Methods A total of 100 patients with syphilis in Department of Neurology， Xixi Hospital of Hangzhou from February 2020 to January 2022 were retrospectively analyzed. There were 50 cases in neurosyphilis group and 50 cases in non-neurosyphilis group. 50 health examinees from our hospital in the same period were selected as the control group. The levels of CD3+ ， CD4+ ， CD8+ of T-lymphocyte and the ratio of CD4+ /CD8+ were compared among the three groups. The value of T-lymphocyte subsets in peripheral blood in identifying early neurosyphilis was analyzed by using the receiver operating characteristic （ROC） curve. Results The levels of CD4+ T-lymphocytes in the neurosyphilis group， the non neurosyphilis group and the control group were （30.48±4.08）%， （32.16±4.08）% and （34.50±4.49）%， respectively， and the CD4+ /CD8+ ratios were （1.25±0.19）， （1.35±0.25） and （1.47±0.23）， respectively. The differences among the three groups were statistically significant （F=11.428， 11.970； P ＜ 0.01）. The differences between every two groups were statistically significant （P＜ 0.05）. The patients in neurosyphilis group were divided into early group （n=30） and late group （n=20） and compared with the control group. The results showed that the levels of CD4+ T-lymphocytes were （31.23±4.28）%， （29.35±3.57）%， （34.50±4.49）%， and the CD4+ /CD8+ ratios were （1.29±0.21）， （1.18±0.13）， （1.47±0.23）， respectively. There was a statistically significant difference among the three groups （F=12.289， 15.350； P＜ 0.01）. The CD4+ T-lymphocyte level and CD4+ /CD8+ ratio in the late stage group were lower than those in the control group， and the CD4+ /CD8+ ratio was lower than those in the early stage group， with statistically significant differences （P ＜ 0.05）. The area under the ROC curve （AUC） predicted by CD4+ /CD8+ ratio was 0.725 （95%CI：0.645-0.805）， higher than that of CD3+ ， CD4+ and CD8+ . Conclusions The significant decrease of CD4+ level or CD4+ / CD8+ ratio is highly suggestive of neurosyphilis， CD4+ / CD8+ is more helpful for early identification of neurosyphilis.

Abstract:Dopamine supersensitivity psychosis （DSP） refers to the development of rebound psychosis， increased drug tolerance， and tardive dyskinesia （TD） after chronic and high dose of antipsychotic drugs in patients with schizophrenia. The mechanism of DSP is currently unclear， and there is a lack of effective treatment. However， the prevalence of DSP remains high in patients with schizophrenia， especially in treatment-resistant schizophrenic patients. Many clinical studies have focused on DSP in recent years. Mastering its mechanisms of occurrence and effective treatment can shorten the disease course and improve the overall prognosis of patients. Therefore， this paper presents a review of the pharmacological mechanisms and treatment of DSP.

Abstract:Obstructive sleep apnea hypopnea syndrome （OSAHS） is a sleep disorder. It is known that age （65 years or older）， male， obesity and abnormal airway anatomy can lead to the pathogenesis of OSAHS， but the etiology and pathogenesis of cognitive and behavioral damage caused by OSAHS are still unclear. In recent years， studies have found that the prefrontal cortex is closely related to the occurrence of cognitive and behavioral damage of OSAHS. Timely detection of specific damage in prefrontal cortex can be used as an early biomarker. Pathological changes in OSAHS interact with prefrontal cortex injury to form a vicious circle and promote the progress of cognitive and behavioral damage in OSAHS. The changes of molecular level and microstructure of prefrontal cortex in preclinical and clinical stages can be found by neuroelectrophysiological and neuroimaging techniques. This paper briefly describes the progress of the mechanism and detection methods of prefrontal cortex in OSAHS cognitive and behavioral damage in recent years， and discusses the future research direction.

Abstract:Myocyte enhancer factor 2 （MEF2） is widely distributed in the nervous system. MEF2 protein and its related signal pathways play an important role in human physiological and pathological processes. As a key neurodevelopmental factor involved in neuronal differentiation， synaptic connection and transmission， and neuronal survival， up regulating MEF2 activity can play a neuroprotective role and prevent neuronal apoptosis to a certain extent. In recent years， MEF2 has become a risk gene for a variety of neurological diseases， especially for neurodegenerative diseases. This paper reviews the structure， biological function of MEF2 and its relationship with neurological diseases， in order to find new targets for the treatment of related diseases.

Abstract:Circadian rhythm is a series of biological processes that oscillate within about 24 hours and are regulated by clock genes， whose synchronization is critical to the physiological homeostasis of molecular， cellular， organ systems and the whole organism. Acute ischemic stroke shows a temporal trend of circadian rhythm. Related studies suggest that circadian rhythm disturbance may be an important risk factor for acute ischemic stroke， and intervention for acute ischemic stroke may have a time-dependent effect. This review discusses the mechanisms of circadian rhythm involvement in acute ischemic stroke and outlines future research directions

Abstract:Subthreshold depression refers to a condition in which individuals have certain depression symptoms without meeting the full criteria for major depression disorder（ MDD）. Although the symptoms of subthreshold depression are not as serious as MDD， the prevalence rate of subthreshold depression among individuals is higher than that of MDD， which seriously affects individuals' mental health and social function. Subthreshold depression is considered as a high risk factor for MDD， but its neuromechanism and intervention is not clear at present. Combined with previous research results， this paper reviews the neuromechanism and intervention of subthreshold depression， analyzes the deficiencies and developmental direction of current studies， in order to provide some reference for future studies.

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