Volume 96  ·  Issue 11  ·  2016

Cushing's Disease (CD) was first described by Harvey Cushing in 1932. It is Cushing's syndrome caused by pituitary corticotropic hormone (ACTH) adenoma. The clinical manifestations are full moon face, buffalo back, hyperemia, purple skin lines, hypertension, diabetes and osteoporosis. Cushing's disease accounts for about 10% of pituitary adenomas, with an incidence of 1.2-2.4 million^－1· Years^－1It occurs in women between 25 and 45 years old. Although it is a rare disease, its diagnosis and treatment are relatively difficult. If the patient's high cortisol status cannot be controlled in time and effectively, the probability of multiple complications, such as mental abnormalities, pulmonary infections, thrombosis and cardiovascular and cerebrovascular accidents, will increase, and the natural life span will be significantly shortened. Before the 1950s, the survival time of patients with Cushing syndrome was only 4.6 years due to the lack of effective treatment^[1]。 Now, 60 years later, the standardized mortality rate of patients with Cushing's syndrome is still 1.7 to 4.8 times that of the normal population^[2,3]The mortality rate of patients with persistent or recurrent hypercortisolemia is significantly higher than that of the normal population^[4,5]It has brought a great impact on patients' health, marriage, family and society.

Cushing syndrome (CS), also known as hypercortisolism, is a syndrome with typical manifestations of centripetal obesity, hypertension, abnormal glucose metabolism, hypokalemia and osteoporosis caused by hypercortisolemia caused by various etiologies, acting on target organs. According to foreign literature reports, the annual incidence of CS is 2~3/10⁶with a prevalence of about 40/10^6[1,2]。 From the etiological classification, CS can be divided into adrenocorticotropic hormone (ACTH) -dependent and ACTH-independent. The former includes pituitary ACTH-secreting adenomas and ectopic ACTH-secreting tumors, accounting for 70%-80% of the etiological causes; The latter is caused by the spontaneous secretion of excessive cortisol by adrenal tumors (adenomas and adenocarcinomas) or hyperplasia, accounting for 20% to 30% of the etiology. Pituitary CS, also known as Cushing's disease (CD), is the most common cause of CS, accounting for about 70% of the total number of patients.

To analyze inferior petrosal sinus sampling (IPSS) in diagnosis and treatment of Cushing's disease with negative magnetic resonance imaging (MRI).

We retrospectively reviewed 79 cases of Cushing's disease with negative MRI in the Department of Neurosurgery of Peking Union Medical College Hospital from August 2012 to August 2014.Of the 79 patients, 58 underwent IPSS.There were 16 males and 42 females in this study, with age 12 to 65 years old.All 58 patients underwent endocrine assessment before transsphenoidal surgery, and pathology specimens were examined.

The IPSS results of all the 58 patients suggested the excessive secretion of ACTH was from pituitary.Of the 58 patients, visible tumor was found in 56 cases during intraoperative exploration (96.6%). In 29 (50%) cases, the sideof pituitary where tumor was located predicted by IPSS was the same with intraoperative exploration.Typical tumorwas seen in 47 cases during exploration, and the endocrine remission rate was 83.0% after operation.Suspicious tumor was seen in 9 cases, and endocrine response rate was 44.4%.No tumor was found in two caseswhohad no remission after operation.Pituitary adenoma was confirmed in 41 patients (70.7%) by pathological exam.And anterioror posterior lobe of pituitary was reported in 12 cases, pituitary hyperplasia in 5 cases.

IPSS is recommended in Cushing's disease patients with negative MRI, and it is helpfulto judge whether the excessivesecretion of ACTH is from pituitary, whileits value in predicting the lateralization of tumor is low.If IPSS results are positive, transsphenoidal surgery should be performed.

Toinvestigate the value of desmopressin(DDAVP)stimulation test and high dose dexamethasone suppression test(HDDST) inestablishing the cause of ACTH dependent Cushing's syndrome.

The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed.The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard.

A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively.The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test.When the two tests had consistentresults, the diagnostic accordance rate was 100%.

DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease andectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

To compare and analysis blood coagulation index change and influence factors in Cushing's syndrome (CS) and obesity (OB) patients to provide theoretical evidence for improving the prognosis of them.

A total of 250 patients with CS and 164 patients with obesity were collected from October 2012 to August 2015 in Peking Union Medical College Hospital.Peripheral blood cells, liver and kidney function, blood lipid, 24 h urine free cortisol (24 hUFC) and blood coagulation were tested.

The proportion of patients with abnormal blood coagulation indexes were 80% (200/250) and 52% (85/164) respectively in CS and OB patients.Compared with OB patients, coagulation and fibrinolysis values decreased significantly in CS patients.In addition, the shortening of activated partial thromboplastin time (APTT) was more obvious in CS patients, while 24 hUFC, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) were higher than OB.In OB patients, body mass index (BMI), fasting blood-glucose (FBG), TC and LDL-C were associated with blood coagulation abnormalities; in patients with CS, alanine aminotransferase (ALT), aspartate aminotransferase (AST), 24 hUFC, white blood cell (WBC) and platelet (PLT) were associated with blood coagulation abnormalities.

Higher coagulation state in CS is likely relevant to higher level of TC, LDL and cortisol hydrocortisone which, in return, have impact on the blood coagulation system, therefore, the risk of thrombosis in CS patients is increased.

To report the presentation, clinical course and prognosis of myasthenia gravis (MG) with thyroid disease.

Retrospective data analysis was conducted.Between 2004 and 2013, we reviewed a total of 106 patients with MG.We analyzed the clinical features, the relationship between the thyroid function, antibodies and the clinical course, prognosis.

(1)In our study, 20/106 (18.87%) patients were thyroid function-abnormal, 37/106(34.91) were thyroglobulin antibodies (TGAb) and/or thyroid microsomal antibody (TMAb)-positive, and abnormality was observed in 46 (43.40%) of the thyroid gland. Thyroid antibody positive rate was higher than abnormal thyroid function rate, and the difference was significant (P=0.036). (2)The thyroid stimulating hormone (TSH) level( (2.9±4.0) mIU/L) of ocular MG was higher than the level ((1.5±1.1) mIU/L) of generalized MG (P=0.01). (3)The transformation time of 52 ocular type to generalized type was longer in higher antibody group than in normal group (P=0.04). And there were no significant differences between the elevated TSH type and the normal TSH type, the abnormal thyroid function type and normal thyroid function type, the abnormal thyroid type and the normal thyroid type.(4)Comparing the TSH level, total antibody level, TGAb, and TMAb level between the ease group and the unease group in the course of 1 year, 2 years, 5 years, there were no significant differences (all P>0.05).

MG is often companied with thyroid abnormalities.MG patients are more susceptible to hashimoto thyroiditis and other autoimmune thyroid diseases.Ocular type patients are more likely to suffer from thyroid function decrease than the generalized type.MG patients with hashimoto thyroiditis and other autoimmune thyroid diseases are more sensitive to respond to therapy means like glucocorticoid therapy, and the short-term prognosis is relatively good.There are no significant correlations between the MG remission rate and TSH level, total antibody level, TGAb and TMAb level.

To investigate the clinical characteristics, electrophysiological findings and treatment response of Lewis-Sumner syndrome (LSS).

Data of nine patients with LSS, who were diagnosed and treated from May 2008 to August 2014 in Department of Neurology, Peking University Third Hospital, were analyzed retrospectively, including clinical features, electrophysiological studies, pathological characteristics, therapy and follow up.

The nine cases included seven males and two females, with the average age being 29 years old (18-64 years old). The follow-ups after treatment were between 6 months to 48 months.All 9 cases were asymmetrical onset, and the distal part of limbs was initially affected in 8 cases.Five cases presented with the initial symptom of sensorimotor, 3 cases with purely motor and only 1 case with sensory.The disease developed two forms: multifocal distribution and symmetrical distribution.Electrophysiological studies demonstrated conduction blocks on non-entrapment sites, involving mainly median nerve and ulnar nerve.Sural nerve biopsy presented mild demyelination without inflammatory infiltration.The symptoms of patients had some degrees of improvement after immunotherapy, and the prognosis was favorable.

Lewis-Sumner syndrome presents the initial symptoms of asymmetrical sensorimotor neuropathy mostly affecting the upper extremities.Median nerve and ulnar nerve are the most common involvements. Electrophysiological studies demonstrate motor nerve conduction block.The major finding of pathology is mild demyelinated.The patients have a positive response to immunotherapy.

The study aimed to analyze the influencing factors of thrombolysis therapy in acute ischemic stroke patients with onset time less than 4.5 hours.

We consecutively prospectively screened acute ischemic stroke patients with onset time less than 4.5 hours from emergency department, outpatients and inpatients of neurology department, and image center in our hospital over a 31-month time period (April 2012-November 2014). The rate of thrombolysis and the reasons for not receiving thrombolysis were analyzed.

A total of 538 patients who met the inclusion criteria were included (68.2% males, mean age 67±13 years old). Only 104 (19.3%) patients received thrombolysis. The main reasons for the patients not receiving thrombolysis included minor symptoms (172 cases, 39.6%), rapidly improving symptoms and high possibility of transient ischemic attack (TIA) (59 cases, 13.6%), patients or families refusing thrombolysis (44, 10.1%), in-hospital delay (38, 8.8%), elderly people with age over than 80 years old (38, 8.8%).

The thrombolysis rate within time window of acute ischemic stroke is remarkably higher than that of several years ago in China.The main reasons for not receiving thrombolysis are minor and rapidly improving symptoms, patients or families' refusal, in-hospital delay, elderly people with age over than 80 years old.

To investigate the change of regional homogeneity(ReHo)in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS)using resting-state functional magnetic resonance imaging(fMRI).

Resting-state fMRI data were collected from 15 patients with OSAHS and 15 normal controls.Patients were enrolled from the Sleep Laboratory of the Otolaryngology-Head and Neck Surgery Department of Zhongda Hospital, Southeast University, Nanjing from November 2014 to June 2015.The data were analyzed with the ReHo method and compared between OSAHS and controls.

The ReHo showed a significant increase in the posterior lobe of right cerebellum (t=4.292 1, P<0.01), posterior lobe of left cerebellum (t=4.350 6, P<0.01), right brainstem (t=5.276 6, P<0.01), right occipital lobe (t=3.620 9, P= 0.001), left basal ganglia (t=3.385 6, P=0.002) and left temporal lobe (t=4.781 2, P<0.01) and a decrease in the right middle frontal gyrus (t=-3.564 4, P= 0.001), right inferior parietal lobe (t=-4.123 7, P<0.01) and bilateral superior frontal gyrus (t=-3.500 9, P=0.002) in patients with OSAHS.Furthermore, the average ReHo values of the posterior lobe of bilateral cerebellum was positively correlated with the MMSE scores(r=0.682, P=0.012), the LMT scores (r=0.623, P=0.013) and the LMT-delayed recall scores(r=0.577, P=0.024), while negatively correlated with the TMT-A scores (r=-0.723, P=0.002); the average ReHo values of the right middle frontal gyrus (r=0.661, P=0.007) was positively correlated with the TMT-A scores.

The current findings indicate that significant changes of ReHo in the global brain regions have been detected in OSAHS patients and the compensatory change of brain function occur.Abnormal ReHo values in the posterior lobe of bilateral cerebellum and right middle frontal gyrus could serve as potential biomarkers for assessment of neuronal damage and further provides insights into the biological mechanism of the disease.

To evaluate the clinical effectiveness of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in single-level lumbar degeneration disease treatment.

We retrospectively analyzed the clinical data of 32 patients who underwent the MIS-TLIF surgery from Nov.2013 to Oct.2014 in Shanghai Tongji Hospital.Clinical and radiological outcomes including operation time, X-ray exposure, surgical blood loss, drainage blood loss, complications, visual analogue scores (VAS), Oswestry disability index (ODI) scores, average intervertebral space and fusion rate.VAS scores of low back and leg pain, ODI scores were recorded before and after surgery to evaluate the functional recovery, average intervertebral space height, lumbar and surgical Cobb angle were measured by X-rays before and after surgery to assess recovery of intervertebral space height and the change of lumbar kyphosis.The Bridwell criterion was used for evaluating the interbody fusion and the MacNab criterion was used for assessment after surgery.

All the patients received successful surgery.The mean operative time was (171.9±31.1) min with (36.7±16.4) seconds radiation exposure, and mean blood loss was (153.3±64.8) ml, drainage blood loss was (58.9±49.2) ml.All cases were followed up for (11.6±3.3) months.Compared with preoperation, VAS score of low back and leg pain, ODI score and average intervertebral space showed significant improvements after surgery.There were 26 (81.3%) cases were grade Ⅰ and Ⅱ 3 months after surgery according to the Bridwell criteria while the number was 31 (96.9%) at the last follow-up.The clinical results were excellent in 22 cases, good in 8 cases and fair in 2 cases according to the MacNab criteria at the final follow-up.

MIS-TLIF under Spotlight work channel system is a safe and effective procedure for single segment lumbar degenerative disease and it may offer patients additional advantages in less trauma and reduction of hospital stay.

To explore correlation between shifting of gravity center position (GCP) and functional recovery after total hip arthroplasty (THA) in patients who suffered from avascular necrosis of the femoral head.

Eighty six patients (49 right hip, 37 left hip) with avascular necrosis of the single femoral head who underwent THA at our department from January 2011 to December 2013 were investigated.Each patient was evaluated with Harris score system and measured GCP by corresponding instrument preoperatively and six month, one-year postoperatively.Pearson's correlation analysis was used to analyze the correlation between shifting degree of GCP and changing degree of Harris score at the above time points.

Harris score significantly improved after surgery (P<0.01), and there was a direct linear relationship between shifting degree of GCP and changing degree of Harris score at the same period after the surgery, and the adjustedR² value between them were 0.521 at six month and 0.46 at one year after operation.

As the function of the hip recovers, the GCP moves from its initial position to the operative side after THA. The shifting degree of GCP can be a reflection of recovery of the joint function in some extent.

To analyze the clinical and laboratory features of psoriatic arthritis (PsA) which antedates psoriasis.

The clinical and laboratory data including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), immunoglobulins, antibodies of 113 patients with PsA were analyzed retrospectively and compared by order of the occurrence of arthritis.

The occurrence of psoriatic arthritis which antedates psoriasis was 22.1% in the study. The onset of arthritis was 2 months to 25 years earlier than psoriasis. Arthritis of distal interphalangeal (DIP) joints was frequently involved in this group and arthritis of hip joints was rare. Positive HLA-B27 and higher level of platelet (PLT), ESR, CRP, and IgA were common in patients with psoriatic arthritis which antedates psoriasis.

Arthritis of DIP joints and elevated inflammatory markers are frequently involved in patients with psoriatic arthritis which antedates psoriasis, and somewhat they are associated with disease activity.

To examine the neuroprotective effects of FGF-2 and explore the underlying mechanisms involved in its effects on neural precursor cells (NPCs) and S-IR boutons.

The mice models were established, and the animals were randomly divided into 3 groups: non-transgenic wild type group (WT), superoxide dismutase (SOD)1 G93A G1H transgenic group (SOD1), and fibroblast growth factor (FGF)-2-treated group (FGF-2), each group 40 mice.Mice of FGF-2 group were treated with FGF-2 at postnatal day 60 (P60). These three groups were examined at postnatal day 90 (P90) and 120 (P120). The changes of NPCs and S-IR boutons were checked by means of immunohistochemical detection.

When mice were examined at P90 and P120, the number of Nestin⁺ NPCs was (47±24) and (147±45) in the SOD1 group, (77±27) and (285±103) in the FGF-2 group.A marked increase was detected in the FGF-2 mice compared to the SOD1 mice at P120 (P<0.01). At P120 there was a clear decrease in the density of S-IR boutons in the SOD1 (0.5±0.1) and FGF-2 (0.8±0.1) mice compared to the WT (0.9±0.1) mice, but a more significant decrease in the density of S -IR boutons was detected in the SOD1 mice compared to the FGF-2 mice (P<0.05).

FGF-2 may be a useful treatment to provide neuroprotection against neurodegeneration in amyotrophic lateral sclerosis (ALS) by encouraging the proliferation of NPCs and delaying the decrease in the density of S-IR boutons.

To explore whether nuclear translocation of β-catenin affects functional expression of sodium iodide symporter (NIS) in human thyroid cancer cells.

Two kinds of β-catenin nuclear translocation cell models were firstly established with transfection of hypoxia inducible factor 1α (HIF-1α) and β-catenin cDNA in human thyroid cancer cell line FTC133.Then the expression of β-catenin were further interfered by shRNA in above two cell models.After that, the influence of β-catenin nuclear localization on the functional expression of NIS, iodine uptake potency, epithelial-mesenchymal transition (EMT) characteristics, tumor growth curve and treatment effect inducing by radioactive iodine were comparatively analyzed in vitro and in vivo trials.Additionally, the underlying mechanism of NIS functional expression was also assessed via identifying the activation of β-catenin signal pathway.

In vitro assay showed prominent EMT phenotype in the above two β-catenin nuclear translocation cell models, and in vitro proliferation and invasion potential of cancer cells markedly increased (all P<0.05); NIS protein expression translocated from cell membrane to cytoplasma.Cell iodide uptakein vitro decreased about 50.0% and 37.5%, respectively in above two β-catenin translocation cell models (both P<0.05). Moreover, β-catenin nuclear translocation was correlated with phosphorylation expressions of β-catenin Ser45, Y654 and GSK-3β Ser9. Most importantly, all above changes associated with β-catenin nuclear translocation could be effectively reversed after blockade of β-catenin expression.In the animal model, tumor growth potential and tumor mass were significantly inhibited by both blockade of β-catenin and radioactive iodide (¹³¹I) (all P<0.05). Meanwhile, immunohistochemistry demonstrated that β-catenin nuclear translocation remained in subcutaneous tumor cells after transplantation, and showed negatively associated with NIS membrane expression.

β-catenin nuclear translocation is a vital regulatory pathway involved in functional expression of NIS in human thyroid cancer cells.

To evaluate the effects of lipopolysaccharide (LPS) and dexamethasone on function of hypothalamus-pituitary-testis axis and to explore the possible underlying mechanisms.

LPS (100 μg/kg), dexamethasone (DEX, 1 mg/kg) and phosphate buffer saline (PBS) were injected subcutaneously into castrated mice ( n=5 in each group) for 4 weeks.The expression of Kisspeptin and its receptor GPR54 in hypothalamus were measured by immunohistochemistry, and plasma luteinizing hormone(LH) were measured by chemiluminescence immunoassay.

After LPS and DEX were administered for 4 weeks, the LH level in LPS group and DEX group was (1.79±0.74) U/L and (2.19±0.60) U/L, respectively, which were lower than PBS group (4.87±1.25) U/L (all P<0.01). In LPS group, after treatment, the kisspeptin immunohistochemistry index in hypothalamus was 4.2±1.1, which was lower than the control group (10.2±1.6,P<0.05). The GPR54 immunohistochemistry index in hypothalamus was 3.6±0.5, which was lower than PBS group (6.2±1.8,P<0.05). In DEX group, the expressions of kisspeptin and GPR 54 in hypothalamus did not change after treatment.

LPS may downregulate function of hypothalamus-pituitary-testis axis through Kisspeptin/GPR54 system.Dexamethasone could suppress function of gonadal axis as well, while the underlying mechanism is still unclear.

The 61-year-old male was admitted to the Department of Endocrinology of Peking Union Medical College Hospital on March 16, 2015 due to fatigue, anorexia for 9 months, polydipsia and polydipsia for 7 months. The patient experienced asthenia with anorexia without obvious trigger in June 2014. Polydipsia, polydipsia and polyuria occurred in August 2014. He drank about 6 L of water a day, and he needed to drink water at an interval of 40 min ~1 h between the days. The urine volume was equivalent day and night. In December 2014, the serum sodium was 127.9-134.7 mmol/L, the tumor markers were negative, and the total serum cortisol (8:00 am) was 31.8-59.8 μ g/L (normal reference value: 87.0-224.0 μ g/L); blood adrenocorticotropic hormone (ACTH) (8:00 am) 2.40 pmol/L (normal reference value: 0-10.13 pmol/L); Thyroid stimulating hormone (TSH) 0.11 mU/L (normal reference value: 0.34~4.00 mU/L), free thyroxine (FT₄) 7.0 pmol/L (normal reference value: 9.0-23.5 pmol/L), free triiodothyronine (FT₃) 2.6 pmol/L (normal reference value: 2.3-6.8 pmol/L); Luteinizing hormone (LH) 0.564 U/L, follicular estrogen (FSH) 0.309 U/L, testosterone 0.219 μ g/L, urine specific gravity 1.005-1.010, blood osmotic pressure 270-288 mOsm/kg H₂O; The erythrocyte sedimentation rate (ESR) was 31 mm/1 h, and the serum immunoglobulin G (IgG) was 65.60 g/L (normal reference value: 7.51-15.60 g/L). Chest CT scan showed no abnormalities in both lungs, and mass-like shadows were seen in the right posterior inferior mediastinum, with uniform density and no enhancement (FIG. 1A)。 MRI of the head and pituitary gland showed thickening of the nasopharyngeal soft tissue, slightly shifting of the pituitary stem to the right, local thickening and nodular shape, and disappearance of hypersignal in the posterior pituitary lobe (Figure 1C)。 No abnormalities were observed in bone puncture.¹⁸F-deoxyglucose (FDG) positron emission computed tomography showed: (1) right posterior mediastinal nodular shadow with uneven increase in FDG metabolism [maximum standard uptake value (SUV_max) 4.9], bilateral cervical, axillary, mediastinal, bilateral hilar, abdominal, retroperitoneal multiple lymph nodes (SUV_max3.7)； (2) Small nodules in the chiasmatic area of the suprasellar cistern, with slightly increased FDG metabolism and slightly thickened pituitary stem; (3) Inflammatory or physiological uptake of FDG in the right wall of nasopharynx. Nasopharyngeal soft tissue biopsy: (nasopharyngeal) mucosal chronic inflammation, bronchoscopy: no abnormality under microscope, (right lower lobe basal segment opening) no cancer cells found in smear; No metastatic carcinoma was found in concurrent biopsy of enlarged lymph nodes. He was diagnosed as "central diabetes insipidus, anterior hypopituitary function, lymphoma?", and was given prednisone 5 mg/time, 2 times/d orally, levothyroxine sodium tablets 50 μ g/time, 1 time/d orally, and desmopressin acetate tablets 0.1 mg/time, 2 times/d orally for replacement therapy. Water drinking and urine volume were reduced, and fatigue and anorexia were significantly relieved. Past history: Diagnosed with type 2 diabetes in December 2014, dietary control, no medication; Complete right bundle branch block, hyperlipidemia, fatty liver, hypertension, multiple polyps of the gallbladder, multiple gallbladder stones. Family history: Two older brothers died of lung and esophageal cancer, respectively, and the older sister suffered from diabetes.

Autism spectrum disorder (ASD) is based on symptoms defined by behavior and is mainly divided into classical ASD and syndromic ASD. Usually referred to as autism generally refers to classical ASD, that is, behavior strictly conforms to the two core symptoms of ASD. According to the definition of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), the latest diagnostic criteria for mental disorders issued by the American Mental Illness Association (APA), these two core categories of symptoms include: deficits in social communication and social interaction; A limited, repetitive behavior, interest, or activity. DSM-5 also no longer distinguishes between subtypes of autism (that is, it no longer lists classical autism, Asperger's syndrome and pervasive developmental disorders separately), but classifies ASD into three grades according to the different severity of the two types of symptoms, with the third grade being the most severe and the first grade being the least severe. A medical disease of known pathology or etiology (e.g. fragile X syndrome, Reye syndrome, tuberous sclerosis) with clinical manifestations of behavioral symptoms consistent with ASD, that is, so-called syndromic ASD, is particularly indicated by the presence of a known medical disease or genetic condition. According to the results of the ASD epidemiological survey released by the Centers for Disease Control and Prevention (CDC) in March 2014, the incidence of ASD in 8-year-old children has reached 1/68. At present, there is no large-scale formal ASD epidemiological survey data in China.

Amblyopia is the most common disease that causes visual impairment in children, with an incidence of 0.3% ~5%^[1,2,3,4]。 It simultaneously becomes one of the common vision impairments in adults due to its late detection or untimely treatment. Amblyopia was previously considered to be a disease with "normal ocular structure", but studies based on animal experiments and human visual electrophysiology have shown that^[5]Amblyopia will have a decline in visual cognition, as well as other effects of various visual functions. Abnormal microscopic anatomy was found in the retina, lateral geniculate body and visual cortex^[5,6,7,8,9]。 The widespread application of optical coherence tomography (OCT) makes intuitive quantitative measurement of retinal structure possible.

Osteosarcoma is the most common among malignant bone tumors^[1,2], more common in children, more common in lower limbs, femoral metaphysis as the prevalent site^[3,4]。 Preoperative and postoperative chemotherapy plus extensive resection of surgical lesions were used clinically^[1]Amputation is mostly used, and now more than 80% of patients with osteosarcoma use limb-saving surgery^[2,5,6,7]and has become a routine treatment for malignant bone tumors of the limbs^[8,9]。 Limb-saving surgery can control the disease and improve the function of the affected limb to a considerable extent, and there is no significant difference in the survival rate between amputation and limb-saving surgery^[2]。 Current surgical methods include tumor prosthesis, bone cement reconstruction, epiphyseal traction, allogeneic bone inactivation and replantation^[10]Autologous fibula reconstruction, autologous tumor segment bone inactivation and replantation, etc. The cost of tumor prosthesis is high, and the prosthesis is infected and loosened after operation. It needs to be revised after long-term use, especially in children, with the possibility of multiple revisions. Allogeneic bone inactivation and replantation have adverse effects such as postoperative nonunion, fracture, infection and postoperative rejection^{[10,11,12,13]}At the same time, there is also transmission of blood diseases, etc^[14,15]。 Autologous bone inactivation is perfectly matched in immunology and anatomy, and reduces the economic burden of purchasing allogeneic bone for patients. If it can be fully inactivated and minimize the damage to tumor bone during inactivation treatment, it is of great significance for patients to recover limb function and prognosis as soon as possible after operation^[16]。 The commonly used methods of autologous bone inactivation include liquid nitrogen, high temperature boiling, absolute ethanol immersion, irradiation and in situ microwave inactivation^{[17,18,19,20,21,22]}Etc. In recent years, the application of hypertonic saline for autologous bone inactivation and replantation has unique advantages for bone healing after replantation because of its simple operation.