Abstract:Alzheimer disease（ AD） is the main cause of dementia. At present， there is no effective treatment plan. The development of new drugs for AD treatment has also been persistently unsuccessful. Therefore， it is of great significance to emphasize AD prevention. In recent years， with the rapid development of biomarkers for the diagnosis of AD， early diagnosis of AD has become increasingly accurate. In addition， there is growing evidence that AD， like other chronic diseases， has many preventable risk factors， and early intervention with these risk factors can help delay or prevent AD. This article mainly discusses the risk factors and pathogenic mechanism of AD， from primary prevention based on identifying and reducing risk factors， to secondary prevention based on early detection of AD pathophysiological characteristics， early diagnosis in the early preclinical stage， and early intervention. The aim of this article is to call for awareness and attention to AD prevention and promote scientific prevention and control.

Abstract:Objective To investigate the abnormality of the node centrality of the white matter network in patients with schizophrenia and its relationship with clinical symptoms. Methods A total of 49 patients with schizophrenia were enrolled in the study. A total of 36 healthy people with matched gender， age and education were selected as the control group. The Positive and Negative Symptom Scales were used to evaluate the clinical symptoms of the patients； the GRETNA software was used to calculate the node centrality values of all subjects； the partial correlation analysis method was used to explore the relationship between the centrality values and clinical symptoms in patients with schizophrenia. Results Compared with the control group， the node centrality of the cerebral white matter networks was abnormal. The degree of centrality in the experimental group was significantly lower in the right insula， precuneus， superior temporal gyrus， left anterior cingulate gyrus， central anterior gyrus， orbital frontal gyrus， parahippocampal gyrus and superior parietal gyrus［ P＜ 0.005， false discovery rate（ FDR） correction］； the degree of centrality of the left anterior cingulate gyrus was negatively correlated with the negative symptom factors（ r=-0.622，P＜ 0.001）. Conclusions The cerebral white matter network of schizophrenia patients has abnormal degree of centrality in multiple brain regions compared with the health control， and such abnormality may be related to the pathophysiological mechanism of schizophrenia.

Abstract:Objective To investigate the effect of raloxifene combined with olanzapine on negative symptoms in postmenopausal women with schizophrenia， and to further analyze the relationship between serum estradiol levels and negative symptoms during treatment. Methods A total of 80 consecutive postmenopausal women with schizophrenia were randomly divided into the study group and the control group according to the random number table. The study group received 12 weeks of olanzapine and raloxifene（ 60 mg/d） treatment， and the control group received olanzapine and placebo treatment. Serum estradiol levels were measured before treatment and at 12 weeks of treatment. Psychiatric symptoms were assessed using the Positive and Negative Symptoms Scale（ PANSS）. Results There was no significant difference in total score of PANSS， positive symptom score P， negative symptom score N， general psychiatric symptom G and serum estradiol level between the study group and the control group before treatment（ P＞0.05）； after 12 weeks of treatment， total score of PANSS and negative symptom score N in the study group were significantly lower than those in the control group （P＜0.05）， while serum estradiol level was significantly higher than the control group（ P＜0.05）. The difference of serum estradiol level before and after the treatment in the study group was positively related to the difference of the negative symptom scores N（ r=0.434，P＜0.05）. Conclusions Raloxifene can significantly improve the negative symptoms of postmenopausal women with schizophrenia and change the serum estradiol content， and the change of estradiol content in vivo may be related to the improvement of negative symptoms.

Abstract:Objective To explore brain magnetic resonance spectroscopy characteristics and their relationship with cognitive impairment in patients with bipolar disorder（ BD） at different clinical stages. Methods A total of 120 patients with BD admitted to the hospital from February 2016 to February 2018 were selected and assigned into stage Ⅱ（ n=28）， stage Ⅲ（ n=47） and stage Ⅳ（ n=45） groups according to their clinical stages. Another 30 healthy individuals were selected as control group. MATRICS consensus cognitive battery （MCCB） was used for all subjects to assess their cognitive function. 1H magnetic resonance spectroscopy（ 1H-MRS） was used to measure BD patients' choline complex（ Cho）， creatine（ Cr） and N-acetylaspartate（ NAA） of frontal lobe， basal ganglia and cerebellum， respectively. The NAA/Cr and Cho/Cr values were calculated， and the relationship between brain biochemical metabolism and cognitive impairment was analyzed. Results （1） With the exception of the scores of the Wechsler Memory Scale（ WMS- Ⅲ）， the scores of other dimensions in BD patients in any stage were lower than those in control group（ P ＜ 0.05）. With the progression of clinical stages， the scores decreased［ stage Ⅳ＜stage Ⅲ ＜ stage Ⅱ（ P＜0.05）］.（ 2） Across the BD patients in different clinical stages， there were no significant differences in the NAA/Cr on the left side of frontal lobe， the Cho/Cr on the left and right sides of frontal lobe， the NAA/Cr on the left and right sides of the basal ganglia， the Cho/Cr on the left side of the basal ganglia， and the NAA/Cr and Cho/Cr on the left and right sides of the cerebellum（ P＞0.05）. The NAA/Cr on the left side of frontal lobe and the Cho/Cr on the right side of basal ganglia in stage Ⅳ group were lower than those in stage Ⅱ group and stage Ⅲ group， with which， the indexes in stage Ⅲ group were lower than those in stage Ⅱ group（ P＜0.05）.（ 3） The NAA/Cr on the left side of frontal lobe and the Cho/Cr on the right side of basal ganglia were positively correlated with the score of Brief Visuospatial Memory Test-Revised （BVMT-R）（ P ＜ 0.05）. Conclusions BD Patients in different stages all suffer from cognitive impairments to some extent， with abnormal brain biochemical metabolism of NAA/Cr on the left side of frontal lobe and Cho/Cr on the right side of basal ganglia that are positively correlated with cognitive function score.

Abstract:Objective To investigate the current procedure of presurgical evaluation and the efficacy and safety of surgical treatment for temporal lobe epilepsy. Methods The clinical data of 27 patients with refractory temporal lobe epilepsy who had operation from August in 2016 to November in 2018 in Shenzhen Second People's Hospital and Shenzhen University General Hospital were analyzed retrospectively. Multiple analysis was used in the presurgical evaluation， including seizure semiology， epileptic sequence of brain MRI （1 mm per slice）， interictal Positron Emission Tomography（ PET）， Video EEG monitoring， epilepsy battery of clinical neuropsychological testing and stereotactic EEG monitoring（ SEEG）. A multi-disciplinary team was involved in the localization and evaluation of epilepsy foci and functional cortex， as well as making the operation plan. Results A total of 13 patients underwent primary resection after noninvasive assessment， and 14 patients underwent surgical resection after SEEG implantation. All patients were followed up for 6-34 months with an average follow-up time of（ 19.93±9.00） months. Surgical efficacy was assessed according to ILAE class criteria. Totally， there were 22 cases of ILAE grade Ⅰ（ 81.48%）， 1 case of ILAE grade Ⅱ（ 3.70%）， 2 cases of ILAE gradeⅢ（ 7.41%）， and 2 cases of ILAE grade Ⅳ（ 7.41%）. The SEEG implantation group had higher ratio of ILAE grade Ⅰ comparing to no SEEG implantation group（ 12/14 vs 10/13）， the MRI positive group had higher ratio of ILAE gradeⅠ than the MRI negative group（ 16/19 vs 6/8）. However， there was no statistically significant difference between the two groups. For complications， one patient had intracranial hemorrhage after SEEG electrode implantation， one patient had delayed intracranial hematoma after anterior temporal lobe resection， two patients had transient oculomotor nerve injury， one patient had poor scalp incision， four patients had post-operation infection. There were no cases of cerebrospinal fluid leakage or visual field damage or any other complications. Conclusions With more detailed presurgical evaluation and SEEG implantation， the outcome of surgical treatment for refractory temporal lobe epilepsy is becoming more effective.

Abstract:Objective To explore the application of intraoperative neurophysiological monitoring （IONM） in dorsal root entry zone（ DREZ） lesioning for chronic neuropathic pain. Methods A total of 10 patients with chronic neuropathic pain were treated with DREZ lesioning with IONM were analyzed retrospectively. Motor evoked potential（ MEP）， somatosensory evoked potential（ SEP） and electromyography（ EMG） were used for intraoperative neuroelectrophysiological monitoring. Clinical data were collected. Results Among the ten patients， six of them had pain after spinal cord injury. SEP， MEP and EMG of both lower limbs were monitored，and nerve roots or cauda equina were confirmed by nerve root traction stimulation. SEP was unrecordable in two patients and MEP was unrecordable in two patients. Four patients suffered from pain after brachial plexus avulsion. Two of them had upper limb amputated， and SEP and MEP of both lower limbs were monitored. SEP and MEP of all the limbs were monitored in unamputated patients， and SEP of the affected limb was unrecordable in one case. Among the ten patients， three patients had transient and more than 50% reduction in MEP， and 2 patients had transient and more than 50% reduction in SEP. Postoperative pain was significantly alleviated in all the ten patients， and the pain relief was greater than 70%. After the operation， four patients had mild hypoesthesia and decreased limb muscle strength. Two patients had mild dysuria. All the postoperative symptoms were transient changes， and no obvious postoperative complications were found. Conclusions The condition of patients undergoing DREZ lesioning is complex， and it is difficult to monitor neuroelectrophysiology during operation. However， the combination of MEP， SEP and EMG can effectively improve the success rate of operation and reduce the complications.

Abstract:Objective To investigate the overall effectiveness and tolerance of low-dose amisulpride combined with escitalopram oxalate in the treatment of depression patients with fatigue symptoms. Methods From September 2017 to June 2018， a total of 100 patients with depression in our hospital were selected as subjects. According to random number table method， the patients were divided into study group and control group， with 50 cases in each group.Tthe control group was given escitalopram oxalate orally， while the study group was given escitalopram oxalate combined with small doses of amisulfapride. Hamilton Depression Scale（ HAMD-17） and Fatigue Severity Scale（ FSS） were used before and after treatment to evaluate the overall treatment effectiveness in the two groups. Results （1）There was no significant difference in general data between the two groups（ P ＞ 0.05）.（ 2）There was no significant difference in HAMD score between the two groups before treatment. After 1， 2 and 4 weeks of treatment， the HAMD score of the two groups decreased significantly， with the study group's score change significantly more dramatically than the control group（ P＜0.01）. （3）There was no significant difference in the FSS scores between the two groups before treatment. The FSS scores decreased in both groups after 2 weeks of treatment， while the change in the score was only significant for the study group（ P＜0.05） not for the control group（ P＞0.05）. At the end of 4 weeks of treatment， the FSS scores in both groups continued to decrease， with the study group's score change more dramatically than the control group. There were significant differences between the two groups in intra-group comparison and inter group comparison（ P＜0.05）.（ 4）The incidence of adverse reactions was 16%（ 8/50） in the study group and 14% （7/50） in the control group. There was no significant difference between the two groups. Conclusions Lowdose amisulfapride combined with escitalopram oxalate is more effective for depression and fatigue symptoms in patients with depression， with similar adverse reactions.

Abstract:Objective To understand the comorbid conditions of physical illness in hospitalized elderly patients over 80 years old with mental disorders. Methods The study screened inpatients from Beijing Anding Hospital affiliated to Capital Medical University from January 1， 2010 to December 30， 2017. Patients with diagnosis based on ICD-10， age of ＞ 80 years old， and complete clinical files were selected. The comorbid conditions of physical illness and other information in the selected patients were investigated. Results Among the 187 patients， 183 patients had physical illness， with a comorbid rate of 97.9% and an average of 6.9 comorbidities. There was no significant difference in the number of comorbid physical diseases among patients with different mental disorders（ P ＞ 0.05）. In terms of the average number of comorbidities， mental disorders and mood disorders caused by brain damage and dysfunction， and other physical diseases had significantly fewer comorbidities than other four types of mental disorders（ P＜0.05）. A total of 183 elderly psychiatric patients had a total of 1 297 cases of physical illness. There are 769 cases of diseases in the nervous system， circulatory system， endocrine system， respiratory system and digestive system， accounting for 59.29% of all cases of physical illness. The top five diseases were hypertension（ 115 cases， 62.8%）， constipation （84 cases， 45.9%）， cerebral infarction（ 71 cases， 38.8%）， diabetes（ 54 cases， 29.5%）， and coronary heart disease（ 48 cases， 26.2%）. The number of comorbidities of physical illness in patients is related to age（ P＜0.01）Conclusions The physical comorbidity of elderly patients over 80 years old with mental disorders is very common. The number of comorbidities is large， with cardiovascular and metabolic diseases accounting for the majority.

Abstract:Objective To explore the whole genome DNA methylation modification of impulsive aggression in patients with bipolar Ⅱ disorder. Methods The Illumina human 450k methylation chip technology was used to analyze the level of methylation of the whole blood genomic DNA samples of 5 cases of bipolar Ⅱ disorder patients with impulsive behavior and 5 cases of bipolar Ⅱ disorder patients without impulsive behavior. The R software was used to preprocess the raw data and select the differentiated methylation loci between sample groups. Finally， the GCBI online analysis software was used to analyze the functional enrichment of different candidate genes. Results （1）There was a difference in the methylation levels between the aggression group and the non-aggression group.（ 2）There was a difference in the distribution of methylation loci on the chromosome between the aggression group and the non-aggression group.（ 3）The differentiated methylation loci were classified by gene annotation classification and CpG island annotation classification， and the differentiated methylation loci were distributed in 11 annotation areas.（ 4）The result of GO analysis showed that the differentiated methylation loci participated in signal transmission and other functions. The pathway analysis showed that the affected function was mainly related with dopaminergic synaptic and chemokine signaling pathway. Conclusions In this study， the whole genomic DNA methylation levels and the distribution of methylated DNA on the chromosome in the aggression group were different from the non-aggression group.

Abstract:Objective To investigate the effects and mechanisms of antidepressants on TNF-α- induced neuronal survival and apoptosis. Methods Mouse hippocampal neuronal cells HT22 were divided into 5 groups： control group， TNF-α group， mianserin group， mirtazapine group and amitriptyline group. The last three groups were first treated with the assigned antidepressant for 30 min. All groups except the control group were then treated with TNF-α for 24 h. The neuronal survival rate of each group was detected by the MTT method. The neuronal apoptosis rate was detected by the Annexin V-FITC/PI double staining method. Expressions of related proteins were detected by the Western Blot. Results Antidepressants increased TNF- α-induced neuronal survival rate， reduced TNF-α-induced cell apoptosis rate， TNF-α-induced cytochrome c release， activities of caspase-9， caspase-3， and Cleaved PARP. However， antidepressants had no significant effect on the activity of caspase-8 in any group. Antidepressants also had no significant effect on the expressions of TNFR1 and TNFR2 or the activity of IKBα and NF-κB p65. Antidepressants increased TNF-α-induced LPA1 and FGFR expression as well as JNK and ERK1/2 activity. Conclusions Antidepressants can promote TNF-α-induced neuronal survival， reduce TNF-α-induced neuronal apoptosis， enhancing the TNF-α- induced expression of LPA1/FGFR pathway and activating JNK and ERK1/2 pathways.

Abstract:Objective To evaluate the effectiveness of agomelatine in the treatment of anhedonia in patients with depressive disorders. Methods A total of 58 subjects were included in the study. All patients were treated with agomelatin（ 25-50 mg/d， variable doses） for 8 weeks. Snaith-Hamilton Pleasure Scale（ SHAPS） and Montgomery-Åsberg Depression Rating Scale（ MADRS） were used to evaluate patients' depression and anhedonia， and the Sheehan Disability Scale（ SDS） and the 5-Item World Health Organization Well-Being Index （WHO-5） were used to evaluate patients' functional impairment and quality of life. Results （1）After 8 weeks of treatment with agomelatin， the clinical response and remission rates of SHAPS were 64.71%（33/51） and 58.82% （30/51）. The SHAPS and MADRS anhedonia factors after the treatment were significantly improved compared to baseline（ P ＜ 0.01）.（ 2）Regression analysis showed that gender， first-episode age and family history of mental illness affected the improvement of anhedonia.（ 3）At the end of 8 weeks of treatment， the improvement of SHAPS and MADRS anhedonia factor was significantly correlated with the improvement of WHO-5 and SDS scores（ P＜0.01）.（ 4）Mediational effect analysis showed that the improvement in anhedonia mediated the relationship between depressive severity and the improvement of social functions. Conclusions Agomelatin has a significant effect on anhedonia in patients with depressive disorder， and the improvement of anhedonia is a powerful mediator for the relationship between depressive symptoms and the improvement of social functions.

Abstract:Objective To evaluate the effects of rehabilitation combined with erythropoietin（ EPO） on nerve repair and expression of glial fibrillary acidic protein（ GFAP） in rats with cerebral hemorrhage. Methods A total of 30 healthy male Sprague-Dawley rats were randomly divided into 3 groups- model group and EPO group and training group， with 10 rats in each group. The cerebral hemorrhage model was established in the three groups. After 24 hours of modeling， rats in the EPO group and the training group were given intraperitoneal injection of EPO， the rats in the training group were also given rehabilitation training， and the model group were injected with the same amount of saline as the amount of EPO the EPO group and the training group received. The rats' nerve repair and hippocampal GFAP expression situation were observed and detected. Results All rats were successfully modeled， the Tarlov scores of the EPO group and the training group at 7 d， 14 d and 28 d after modeling were higher than those of the model group（ P ＜ 0.05）， with the training group significantly higher than the EPO group（ P＜0.05）. At 28 days after modelling， the brain water content， serum IL-6 and TNF-α values， and the relative expression levels of GFAP protein in hippocampus were significantly lower in the EPO group and the training group than in the model group（ P＜0.05）， with the training group lower than the EPO group（ P ＜ 0.05）. Conclusions The combination of rehabilitation training and erythropoietin in rats with cerebral hemorrhage can inhibit the expression of GFAP in hippocampus and the release of serum inflammatory factors， reduce brain edema， and promote the restoration of normal nerve function.

Abstract:Objective To compare the level of awareness of mental health and mental illness prevention knowledge among medical staff with various lengths of service in Baoding and their attitudes toward mental illness. Methods A total of 2 541 community medical personnel who were trained in 25 counties in schizophrenia in the case test was statistically significant in the ＜ 20-year group compared with the ≥ 20- year group（ 52.9% vs 43.1%， χ2=23.17，P＜ 0.001）. The ＜ 20 years group and the ≥ 20 years group scores on mental illness related attitudes were statistically significant［ （34.90±6.42） vs（ 35.59±6.64）， t=2.60， P=0.009］. Conclusions Community medical personnel in Baoding have different levels of awareness of mental health knowledge. It is necessary to strengthen the mental health training for medical staff with longer service time and improve the education of mental illnesses of medical staff with shorter service time. and districts of Baoding were selected as survey samples， and 2 433 questionnaires were actually completed. Using the 20-year mark as the dividing criteria， all participants were divided into 1 246 people in the 20-year group and 1 187 people in the ≥ 20-year group. The Mental Health Knowledge and Mental Illness Prevention Knowledge Awareness Questionnaire， the Case Test and the Mental Disorder Related Attitude Questionnaire were used in the survey and analysis. All questionnaires were formulated by the Ministry of Health's Office of Mental Health Work Indicators Survey and Evaluation Program. Results There was a statistically significant difference in the awareness rate of mental health and mental health knowledge between the ＜ 20-year group and the ≥ 20-year group（ 98.1% vs 94.8%， χ2=19.38，P ＜ 0.001）. The positive rate of positive symptoms

Abstract:Alzheimer disease（ AD） is a progressive neurodegenerative disease， 70%-90% of AD patients have behavioral and psychological symptoms of dementia（ BPSD） at some point in the disease. Studies have shown that mood stabilizers can slow the loss of neurons and neurodegenerative processes and relieve BPSD. Mood stabilizers are often used in the treatment of BPSD and received good clinical effects. However， so far， the research outcomes on mood stabilizer in the treatment of BPSD are inconsistent. Using mood stabilizers to treat BPSD in AD is still off-label drug use. Therefore， the efficacy and safety of mood stabilizers in the treatment of BPSD of AD need to be determined by further scientific research， and the drug use instructions need to be updated as well， to make the treatment of BPSD with mood stabilizer well documented.

Abstract:The epigenetic mechanism of Alzheimer disease（ AD） is attracting increasing attention， and 5-hydroxymethylcytosine involved DNA methylation is an important means of epigenetic modification. Recent studies believe that 5-hydroxymethylcytosine is involved in the occurrence and development of AD. This is a very valuable reference for the further revelation the pathogenesis of AD. This article reviews research on the relationship between 5-hydroxymethylcytosine and AD.

Abstract:Cognitive behavioral therapy is one of the most effective treatments for insomnia， but traditional face-to-face cognitive behavioral therapy has limitations such as space constraints and economic burden. Computerized and Internet-based cognitive behavioral therapy are innovative， networked interactive therapy that enhances the availability and acceptability of cognitive behavioral therapy with simplicity and economics. This article reviews and introduces the theoretical basis， core technology， treatment settings， treatment platform， evaluation indicators， therapeutic efficacy， advantages and limitations of computerized and Internet-based cognitive behavioral therapy， and provide reference for the treatment of insomnia.

Abstract:Subarachnoid hemorrhage（ SAH） is an acute cerebrovascular disease. In recent years， inflammatory responses have been considered to play an important role in SAH and its complications. The NLRP3 inflammasome plays a key role in the inflammatory response with its mechanism yet to be specified. This review focuses on the role and related research of NLRP3 inflammasome in SAH， aiming to provide references for clinical studies and treatment strategies of SAH.

Abstract:Bipolar disorder is a severe mental illness with high recurrence rate， high disability rate， and high suicide rate. However， the pathological mechanisms of bipolar disorder is not yet clear. Some international scholars had made a few new discoveries in light of the recently developed oxidative stress hypothesis. This paper summarizes the research on the level of oxidative stress markers in patients with bipolar disorder in China and abroad.

Abstract:Depression is characterized by long course of disease， high recurrence rate， high disability rate and high suicide rate. As a family member of patients with depression， it is easy to produce a caregiver burden， which in turn negatively affects the mental health of the caregiver， the continuous treatment and prognosis of the patient. The main factors affecting the caregiver's burden can be put into three aspects： caregiver's own factors， patient's clinical factors and economic level. Mental health education， cognitive behavioral therapy and network-based psychological intervention are the current commonly used approaches to reduce the caregiver's burden in China.

Abstract:For about 30% of epilepsy patients on antiepileptic drugs， the progression of epileptic seizures are not completely under control. The treatment for epileptic seizures is difficult and the duration of symptoms is relatively long. The brain lesions such as hippocampal sclerosis can be seen by imaging examination. The drug resistance mechanism of refractory epilepsy is a key topic in current medical research. By investigating the drug resistance mechanism， we can start to provide empirical basis for clinical treatment. In this paper， both Chinese and international research progress of the drug resistance mechanism in refractory epilepsy patients are reviewed and summarized， so as to further understand the disease and provide reference for the future research on targeted treatment strategies.

Abstract:Homocysteine is associated with many diseases， and is also involved in the occurrence and development of mental disorders such as schizophrenia. The level of serum homocysteine in schizophrenic patients is elevated， but the specific mechanism is not yet clear. This article reviews the metabolic mechanism of homocysteine， the relationship between homocysteine and schizophrenia， and the mechanism behind its role in schizophrenia， in order to provide potential avenues for the treatment of schizophrenic patients.

Abstract:Alcohol dependence causes profound damage to brain. Alcohol dependence is associated with brain shrinkage， memory and attention deficits， communication disorders and physical disabilities. Monocyte chemoattractant protein-1（ MCP-1） is one of the key chemokines that regulate the recruitment and activation of monocytes and microglia. Both MCP-1 and its receptor C-C chemokine receptor type 2（ CCR2） are involved in various neuro inflammatory disorders. Recent evidence indicates that alcohol exposure increased the activity of MCP-1/CCR2 in central nervous systems. MCP-1/CCR2 inhibition can alleviate alcohol neurotoxicity by reducing neuro inflammation in the brain and spinal cord. In this review， we discussed the role of MCP-1/ CCR2 signaling in alcohol-induced neuro inflammation and brain damage.

Abstract:Cognitive impairment is characterized as an acquired and progressive manifestation of intellectual impairment. Cognitive impairment includes learning， memory， visual space and other abnormal abilities， leading to progressive memory decline， daily living ability decline， mental and behavioral anti-oxidative stress， anti-inflammatory response， anti-apoptosis， etc.， to explore its mechanism of treatment of cognitive impairment abnormalities and other clinical manifestations. The pathological mechanism of cognitive impairment is complex， including Alzheimer disease and vascular dementia. Currently， the treatment of multiple targets is the key to improve the efficacy of pharmacotherapy， and it is also possesses the most significant position in recent years. Ginkgobiloba has multi-target and multi-channel treatment characteristics. In this review， we will use the main components of ginkgo biloba lactone， namely ginkgolides A， B， C and bilobalide as the entry point， from its