Volume 98  ·  Issue 29  ·  2018

China's brain research program faces major national needs, to study the network structure and working principle of brain cognitive function, focus on the mechanism of major brain diseases, and realize early diagnosis, treatment and intervention of major brain diseases. Facing China's brain research program, the development of clinical neuroscience has ushered in new opportunities and challenges.

Parkinson's disease (PD) is a common degenerative disease of the central nervous system, which was first reported for 200 years. Its prominent clinical manifestations are motor symptoms, such as quiescent tremor, bradykinesia, muscle rigidity, posture and gait instability, etc. In addition, the non-motor symptoms of Parkinson's disease patients have attracted more and more attention, such as olfactory dysfunction, sleep disorders, especially REM sleep behavior disorders, autonomic nervous system dysfunction and cognitive impairment. Current theories suggest that the pathological basis of PD is the accumulation of α-synuclein in patients' cells, which binds to ubiquitin and deposits in the cell body, forming Lewy body, resulting in cell destruction. This pathological damage is especially evident in the dense part of the ventral substantia nigra of the midbrain^[1]。 The study found that the loss of substantia nigra neurons in the brain of patients with Parkinson's disease has reached 70% when typical motor symptoms appear. Therefore, early screening of patients and timely intervention to prevent disease progression when substantia nigra neurons are not obviously involved has become particularly important, which has also become a hot spot in current research.

Parkinson's disease is the most common degenerative disease of central nervous system among movement disorders. The prevalence rate of Parkinson's disease in people over 60 years old in China is 113.9/100,000^[1], about 2 million patients, and increases with age. The main pathological changes of the disease are the loss of dopaminergic neurons and the formation of Lewy bodies in the dense part of substantia nigra, and the main biochemical changes are the decrease of dopamine transmitters in the striatum region. The clinical symptoms include quiescent tremor, myotonia, bradykinesia and postural balance disorder, as well as non-motor symptoms such as anosmia, abnormal sleep behavior during rapid eye movement, constipation and depression. Deep brain electrical stimulation (DBS) is a new method for treating motor nervous system diseases developed in the 1980s. It can avoid serious complications caused by the destruction of nerve nuclei, preserve the opportunity for patients to receive other new therapies later, and can also be adjusted non-invasively after surgery to achieve optimal symptom control and minimal adverse reactions. The "second honeymoon period", which can be provided to patients in addition to drug therapy, is another milestone therapy for the treatment of Parkinson's disease since the invention of Medopa. There have been more than 100,000 DBS implantation patients worldwide. In recent years, with the development of science and technology, DBS has provided new opportunities and challenges for the treatment of Parkinson's disease.

Alzheimer's disease (AD) is a common neurodegenerative disease and the most common type of dementia. Its incidence and disease burden are increasing year by year. There are currently 5.4 million AD patients in the United States, and it will grow to 13.8 million by 2050. The main pathological changes of AD are diffuse atrophy of cerebral cortex, the formation of senile plaque (SP) with β-amyloid (A β) as the main component and neurofibrillary tangle (NFT) with hyperphosphorylated tau protein as the main component, which eventually leads to dementia. At present, there are no effective drugs and methods to prevent or delay the progression of AD. A series of clinical trials targeting A β production and clearance in recent years have failed to achieve the expected efficacy^[1]。 It shows that A β is not a single therapeutic target of AD, and many studies have begun to turn to the study of the relationship between vascular factors and AD. Ischemic injury will increase A β deposition and Tau protein phosphorylation in the brain, which will lead to microglia activation and stimulate inflammatory response. The rodent model of AD found that with the aggravation of ischemia, the key enzyme of A β production-β-secretase-1 (BACE-1) increased, suggesting that ischemic changes may affect the pathological progression of AD. Community-based pathology studies have found that more than 40% of AD patients have AD-like pathological changes and cerebrovascular disease^[2]。 Cerebrovascular diseases include cortical infarction, lacunar infarction, periventricular demyelination, microinfarction, microhemorrhage, atherosclerosis and gliosis. The autopsy study found an interaction between the two lesions. Only 57% of patients with AD-like pathological changes developed clinical dementia. However, if there is a cortical infarction (found by autopsy), 75% of patients develop clinical dementia; If there is also lacunar infarction, up to 93% of patients develop clinical dementia. Therefore, understanding the relationship between vascular dysfunction and A β deposition is crucial to explore the pathogenesis of AD.

Epilepsy surgery is one of the most rapidly developing branches of neurosurgery in recent years. Stereoscopic electroencephalography (SEEG), as an invasive preoperative evaluation method, has been rapidly popularized in North America and China in recent years. The connotation of SEEG is that according to the thinking of "anatomy-electro-clinical", first establish a three-dimensional hypothesis of seizure propagation, and then bury the deep electrode to judge the location of epileptogenic focus to verify the hypothesis, and guide the final surgical resection plan. The related research of SEEG has greatly deepened the understanding of epilepsy symptomatology and epilepsy network; Other diagnostic techniques for localization of epileptogenic foci accompanying SEEG have also made great progress. In addition, the SEEG platform is an important part of human neuroscience research at present.

Schizophrenia is a chronic disabling mental disease, with onset more common in late adolescence and early adulthood (18-24 years old), and the prevalence rate of the population is about 1%. The prevalence of schizophrenia is relatively stable but the outcome is poor. More than 50% of patients have intermittent worsening but long-term symptoms, about 20% of patients have persistent symptoms and functional disability, and the unemployment rate is as high as 80% to 90%. The average life expectancy of patients has decreased by approximately 15 years compared to the general population and is still worsening, with suicide and somatic disease being the leading causes of death in the early and late stages of the disease, respectively^[1,2]。

The brain is one of the mysteries in the unknown field of mankind. In recent years, European and American countries have successively announced the launch of "Brain Project", and China has also started brain science research oriented to exploring the secrets of the brain and overcoming brain diseases. The concept of "brain science" has brought some innovations to the scientific research of mental and neurological diseases: (1) In the past, it has always been believed that mental diseases are pure psychosomatic diseases without neurobiological changes. With the development of various technical means, especially the development of imaging, more and more researches believe that both the onset, diagnosis and treatment of mental illness involve neurobiological basis. (2) In the past, it was thought that mental illness and neurological illness were separated, but now research has found that the pathological manifestations of mental illness are often the early manifestations of neurological diseases. Research related to brain science believes that these two disciplines penetrate each other. There are many common underpinnings between mental illness and neurological disease. Therefore, in the field of "brain science", the neurobiological mechanism of mental illness has made substantial progress. But also closely integrate neurology and psychiatry from basic to clinical research. This paper will discuss the research of depression in the context of "brain science" from the perspective of neurobiology and clinical neurology respectively.

In recent years, the mutual regulation between intestinal flora and host and its important influence on health have gradually been paid attention to by people, especially the discovery of brain-intestine-microbial axis and the continuous exploration of its function, which makes more researches pay attention to the neuroregulatory role of intestinal flora. Studies have shown that intestinal flora is closely related to the occurrence and development of many kinds of neuropsychiatric diseases, such as autism, Alzheimer's disease, drug addiction, stress-related disorders and sleep disorders, etc. This paper briefly reviews the research progress of intestinal flora in neuropsychiatric diseases.

Aneurysm rupture during in-hospital period contributes to the exceedingly high morbidity and mortality of inpatients with untreated aneurysm. However, risk factors for aneurysm rupture during hospitalization were scarcely focused in previous reports. The aim of this study was to investigate the risk factors of aneurysm rupture during hospitalization and to propose clinical strategies improving prognosis.

Patients with intracranial aneurysm (lA) rupture during hospitalization were identified in our prospective cohort of consecutive patients admitted to Beijing Tiantan Hospital between Jan 2014 to Dec 2017. The ruptured cases were randomly paired with control cases without rupture during hospitalization (controlling age and gender) in a proportion of 1∶2 from the cohort. An observational comparative study was conducted between the two groups.

Tevelve cases with IAs rupture during hospitalization were identified among 4 429 cases with IAs. Twenty-four control cases were matched for gender (male∶female=5∶7) and age distribution. A history of pre-hospital aneurysm rupture was indicated as a risk factor for IA rupture during hospitalization (OR=8.333, 95% CI 1.480-46.936, P=0.011). The irregular shape (OR=10.133, 95% CI 1.941-52.902, P=0.005)and an inflow angle<60°(OR=41.800, 95% CI 4.311-405.335, P=0.000)were morphologic factors associated with IA rupture of inpatients.

A history of pre-hospital IA rupture, IAs with irregular shape and an inflow angle <60° were risk factors associated with IAs rupture of inpatients. Unfavorable outcomes were observed in cases with IA rupture during hospitalization. A one-stage hybrid surgical strategy combining diagnosis, evaluation and intervention could reduce the length of preoperative stay, as well as the rupture risk of inpatients with IAs.

To evaluate the effect of stereotactic iodine-125 brachytherapy in the management of adult thalamic high grade gliomas.

Five cases of adult thalamic high grade gliomas (WHO Ⅲ-Ⅳ) were treated with stereotactic iodine-125 brachytherapy and temozolomide chemotherapy at the Second Affiliated Hospital of Zhejiang University School of Medicine between December 2016 and February 2018, assisted with stereotactic plan and radiation therapy planning system.

Pathology revealed anaplastic astrocytoma (WHO Ⅲ, 2 cases) and glioblastoma (WHO Ⅳ, 3 cases). The average amount of iodine-125 implanted was 10.6 seeds. After surgery, the Karnofsky Performance Scale (KPS) was the same as preoperative KPS, and there was no severe surgery related neurological deficits. The follow-up time was from 2 months to 16 months, with an average of 7.8 months. One patient (WHO Ⅲ) without chemotherapy presented with tumor progression 6.5 months later. The other four cases showed tumor stable on MRI.

Stereotactic iodine-125 brachytherapy in the management of adult thalamic high grade gliomas showed satisfactory recent curative effect. Large case studies and long follow-up are needed for further evaluation.

To analyze the risk factors of perioperative complications within 30 days of carotid endarterectomy(CEA) in the treatment of carotid atherosclerosis stenosis(CAS) during 2011-2017, and to discuss the techniques for reducing the perioperative complication rates.

From August 2011 to August 2017, 486 patients with CAS were retrospective included, and 61 of them underwent bilateral CEA, with a total of 547 cases of CEA included. Perioperative complications were collected within 30 days after operation, and the risk factors related to perioperative complications were analyzed by statistical analysis.

In total 547 cases, 12 cases had a postoperative stroke, while 1 case died. A total of 7 cases underwent cranial nerve injury, and 5 cases had an incision related complications. In chi-square test analysis, data suggested that there was a significant difference in the incidence of complications in patients with heart disease, preoperative neurological score difference, contralateral carotid serious stenosis or occlusion and intraoperative shunt in CCA/ICA technique application (P<0.05). In the multivariate Logistic regression, it suggested that poor preoperative neurological score and contralateral carotid serious stenosis or occlusion were independent risk factors for perioperative stroke and death.

Our results showed that CEA is effective to prevent stroke and treat patients with CAS. Patients with poor preoperative neurological score and contralateral carotid serious stenosis or occlusion may increase the risk of postoperative stroke rates.

To determine the clinical value of droplet digital polymerase chain reaction (ddPCR) method to detect plasma circulating tumor DNA (ctDNA) epidermal growth factor receptor (EGFR) mutations in advanced pulmonary adenocarcinoma.

One hundred and thirty six patients with advanced pulmonary adenocarcinoma diagnosed in the Beijing Chest Hospital were collected from May 2015 to April 2017 for initial treatment. EGFR gene mutation in the plasma ctDNA was detected by both ddPCR and amplification refractory mutation system (ARMS) assays. EGFR gene mutation in the tumor tissue was detected by ARMS assay. Patients with EGFR sensitive mutations received first-line oral treatment with EGFR tyrosine kinase inhibitor (EGFR-TKI) drugs. The Kaplan-Meier survival analysis was used to compared the progression-free survival (PFS) in EGFR gene mutated patients detected with different methods.

Total of 111 samples (81.6%) were detected with EGFR gene mutations in 136 tumor tissue samples. In the 111 samples, 48 samples were found with exon21 L858R mutation (48/111, 43.2%), 59 samples were found with exon19 deletion mutations (59/111, 53.2%), and 4 cases were found with other mutations (4/111, 3.6%). Using tumor specimens as the gold standard, the sensitivity, specificity, and concordance rate of ARMS assay were 58.6%, 96.0%, and 65.4%, respectively; and those in ddPCR assay were 79.3%, 100%, and 83.1%, respectively; the coincidence rate was 83.1% (Kappa=0.685, P<0.001). Kaplan-Meier survival analysis showed that patients with EGFR gene mutation detected by both ddPCR and ARMS methods had shortest PFS when compared with those in patients detected positive with a single method of ddPCR or ARMS assay (11.6 moths vs 14.8 months, χ²=2.517, P=0.026).

ddPCR is a reliable technology with high sensitivity and high specificity to detect EGFR gene mutations in plasma ctDNA in patients with advanced pulmonary adenocarcinoma. Plasma EGFR gene mutation may predict the efficacy of EGFR-TKI drugs.

To compare the characteristics of X-ray, CT and MRI of Brucella spondylitis and tuberculous spondylitis and its significance for differential diagnosis.

A total of 10 cases of Brucella spondylitis and 20 cases of tuberculous spondylitis confirmed from the clinical, laboratory or pathological department were enrolled between January 2014 and August 2017 in the Fifth Affiliated Hospital of Sun Yat-sen University and the Third Affiliated Hospital of Southern Medical University. The CT, MRI findings were retrospectively analyzed to improve the differential diagnosis of these two diseases.

Of the 10 cases of Brucella spondylitis, 8 were located only in the lumbosacral vertebrae, 1 in the thoracic vertebrae only, 1 in the cervical and thoracic vertebrae, 8 with invasive bone destruction, and 8 with narrowed intervertebral space. In 9 cases of intervertebral disc destruction, 7 cases developed paravertebral abscesses, 3 cases had sclerotic edges, all cases had no vertebral body flattening, 5 cases invaded the accessory, 4 cases formed sequestrum, and 6 cases invaded the spinal canal. There were 3 cases showing invasion of surrounding muscles. In 20 cases of tuberculous spondylitis, 12 cases were located in the lumbosacral vertebrae, 6 cases in the thoracic vertebrae only, 1 involved the thoracic vertebrae and lumbosacral vertebrae, 1 involved the neck, chest, and lumbosacral vertebrae. Bone destruction of bone, 19 cases of intervertebral space narrowing, 20 cases of intervertebral disc destruction, 18 cases of paraspinal abscess formation, 10 cases of sclerotic edge formation, 6 cases of vertebral body flattened, 16 cases of invading attachment. There were 17 cases of sequestrum formation, 13 cases of invasion of the spinal canal, and 12 cases of violation of surrounding muscles. There were statistical differences between the two types of imaging signs such as the type of vertebral destruction and the presence or absence of sequestrum.

The type of vertebral destruction and the presence or absence of imaging features such as sequestrumwill facilitate the differential diagnosis of Brucella spondylitis and tuberculous spondylitis.

Pelvic fractures are mostly caused by high energy injury, which is the type of fracture with the highest mortality rate. Reconstructing the stability of pelvic ring is particularly important in the treatment of pelvic fractures. External fixation is the gold standard for stabilizing anterior pelvic ring fractures^[1]However, in recent years, many scholars have also used the nail-rod system for the fixation of the anterior pelvic ring, which can not only obtain good stability, but also avoid risks such as needle tract infection of the external fixator^[1,2]。 The fixation of the posterior pelvic ring is also very important. When it is injured, the fatality and disability rate are high. Studies have shown that the use of percutaneous sacroiliac screw is the most widely used and effective treatment for posterior pelvic ring injury^[3]。 Since August 2016, our department has started to use the anterior ring nail-rod system combined with percutaneous sacroiliac screws for minimally invasive treatment of unstable pelvic fractures, and achieved good results, as reported below.

A 79-year-old male was admitted for "blurred vision for more than 6 months and occipital discomfort for more than 4 months". Physical examination: vital signs stable, GCS score 4+5+6, bilateral pupils of equal size and round, sensitive to light reflection, diameter 3 mm. Slight pain and tenderness in the left chest. The breathing sounds of both lungs were thick, not as obvious as dry and wet rales, and there was no difference. Imaging examination: Cranial MRI examination (17 Feb 2017) showed multiple isometric T in bilateral occipital lobes₁Hybrid T₂Signal mass shadow, the larger one is about 4.8 cm ×4.1 cm in size, obviously enhanced after enhancement, with edema signal shadow around it; Mass shadows in superior sagittal sinus and transverse sinus, showing isotonic₁Eq T₂Signal, heterogeneous enhancement after enhancement (Figure 1)。 CT examination of thoracic, abdominal and pelvic cavity (16 February 2017) showed no obvious abnormalities. CTV of the head (21 February 2017) showed filling defects in the transverse sinus, superior sagittal sinus, straight sinus, sinus sinus, and right sigmoid sinus on both sides. Multiple masses and nodules were seen in bilateral occipital lobes, showing obvious enhancement (Figure 2)。 A mass of 4.5 cm ×4.5 cm ×3.5 cm was seen 1 cm below the occipital cortex. After complete resection, it was sent to pathology. Postoperative pathology (April 17, 2017) showed an intracranial space-occupying nodule, 5.0 cm ×4.5 cm ×2.0 cm in size, with intact capsule, gray-white-gray-red cross section, and medium-soft texture. Microscopically, tumor cells grow in patches and diffuses, with round, oval, vacuolar nuclei, coarse granular chromatin, obvious nucleoli, rare nuclear division, few interstitial components, abundant blood vessels, and local bleeding; Immunohistochemical staining revealed CD99 (+), Bcl-2 (+), STAT6 (partially weak +), CD56 (partially +), CgA (-), EMA (-), CK-PAN (-), S-100 (-), VM (-), GFAP (-); The gene test was negative for SS18 gene break, suggesting that the other genes of SS18 were not fused. The pathological and immunohistochemical diagnosis was intracranial synovial sarcoma (Figure 3)。 Three months after surgery, MRI of the skull showed recurrence involving bilateral occipital region and posterior cerebellum.

Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia. It is estimated that there are more than 6 million AD patients in China at present, and it is estimated that it will exceed 20 million in 2050. AD mainly manifests as progressive comprehensive cognitive impairment. With the progression of the disease, patients lose the ability to live independently in the late stage and completely need others to care for them, which brings a heavy economic burden to society and families. It has become one of the challenging public health problems in the 21st century. Therefore, it is of great social significance to clarify the pathogenesis of AD and find effective treatment methods for the etiology. At present, the research on the pathogenesis of AD is in-depth, and the research on the etiology and treatment of AD is continuously advancing although there are setbacks. This article will summarize the research progress of the pathogenesis and treatment of AD in recent years.

With the accelerating aging of the population, the incidence of Alzheimer's disease (AD), the most common type of senile dementia, is increasing day by day, and there is no cure at present, which has become a major public health problem in China! The pathological changes characteristic of AD include amyloid beta (A β) plaques and neurofibrillary tangles. The above two pathological changes lead to neuronal degeneration and death through various mechanisms until the patient develops clinical symptoms^[1]。 A growing body of research evidence suggests that impaired blood-brain barrier (BBB) may be related to AD^[2]。

With the acceleration of China's industrialization, urbanization and aging process, and the improvement of residents' living standards, the causes of death of Chinese residents have also changed. In 2013, the leading cause of death in most provinces was cerebrovascular diseases represented by stroke^[1]。 Cerebrovascular disease is also the second leading cause of death worldwide after ischemic heart disease, and ranks first among many East and Southeast Asian countries^[2]。 Stroke not only causes anatomical damage of brain tissue, but also affects the structure and function of brain network, resulting in neurological and cognitive dysfunction of patients. The existing treatment methods for ischemic and hemorrhagic stroke have limitations, and it is difficult to satisfactorily repair neurological dysfunction. Neural stem cells or other adult stem cells can promote brain tissue repair and reconstruct brain network structure. Neural stem cells play an important role in the process of brain network reconstruction, which is likely to open up new therapeutic approaches for stroke.

Texture analysis is a part of the research field of radiomics. Based on the relationship between pixel or voxel intensity and spatial distribution in conventional images, it can extract, analyze and interpret quantitative image features with high throughput, and objectively and quantitatively assess the overall heterogeneity of tumors^[1,2,3]。 It is not only reproducible but also non-invasive. It has been widely used to differentiate benign and malignant tumors^[4,5,6]Pathological grade^[7]Efficacy evaluation^[8,9]And so on. Pancreatic cancer accounts for 85% ~95% of pancreatic malignant tumors^[10,11]Early diagnosis is difficult, most of them are in the middle and late stages at the time of consultation, with a high mortality rate and a 5-year survival rate of less than 5%^[12]Therefore, early diagnosis is crucial to improve patient survival and prognosis. In addition, different pancreatic tumors may have similar imaging findings, which can easily lead to misdiagnosis. Therefore, accurate diagnosis is of great clinical significance to guide the clinical formulation of personalized treatment strategies and avoid unnecessary surgical resection. Therefore, improving early diagnosis and accurate diagnosis is the key problem in current research. In this paper, the basic concepts of texture analysis, its application in the diagnosis and treatment of pancreatic tumors and its research progress are systematically reviewed.

Parkinson's disease (PD) is a common neurodegenerative disease, with bradykinesia, tremor, rigidity and abnormal gait posture as the main clinical manifestations. The prevalence rate of the elderly over 65 years old in China is about 1.7%. In recent years, the research on Parkinson's disease has made great progress, which has deepened our understanding of the pathogenesis, diagnosis and treatment of PD. This article mainly reviews the development of brain network research and neuromodulation therapy in PD.

During the treatment of neurologically critical patients, it is often necessary to closely and dynamically monitor the neurological status of patients, but routine examinations of arousal level, brainstem reflex and limb movement can only be performed intermittently. Moreover, for patients with coma, sedation and paralysis, the accuracy and reliability of routine neurological examinations are limited. Neuroimaging examination reflects the morphological and structural damage of the brain, but cannot directly suggest functional changes. "Time is the brain", and with the increasing number of interventions to treat or ameliorate nerve damage, high-risk patients need central nervous system monitoring to detect early lesions or neurological deterioration.

Acute respiratory distress syndrome (ARDS) is a common ICU syndrome caused by severe pneumonia, trauma, burn and other diseases inside and outside the lung. In recent 10 years, the mortality rate of ARDS remained high. The incidence rate of ARDS in ICU was as high as 10%, and the mortality rate of severe ARDS was as high as 46%^[1]。 Mechanical ventilation is an important treatment for ARDS, but its complications such as ventilator-associated lung injury (VILI) and ventilator-associated diaphragm dysfunction (VIDD) significantly affect the prognosis of patients. At present, a large number of studies have demonstrated that preserving spontaneous breathing (SB) can improve the ventilation flow ratio (V/Q), improve ARDS oxygenation and reduce ventilator-related complications in patients with ARDS. For patients with mild to moderate ARDS requiring mechanical ventilation, preservation of SB can benefit the patient.