National Medical Journal of China
Volume 93 · Issue 25 · 2013
Natl Med J China
Attention to non-motor symptoms and electrophysiological diagnosis of patients with multisystem atrophy
Expert consensus on the rational use of muscle relaxants (2013)
With the increase of general anesthesia (general anesthesia), the application of muscle relaxants (muscle relaxants) has increased significantly, and the variety of clinical application of muscle relaxants has increased and the experience has accumulated. It is necessary to revise the Expert Consensus on Rational Application of Muscle Relaxants (2009) to guide the more rational and safe application of muscle relaxants.
Comparative study on diagnostic significance of urethral sphincter versus external anal sphincter electromyography in patients with multiple system atrophy
To evaluate the diagnostic value of external anal sphincter electromyography (EAS-EMG) versus urethral sphincter electromyography (US-EMG) in patients with multiple system atrophy (MSA).
A total of 27 MSA patients were examined with EAS and US-EMG as treatment group while 28 non-MSA subjects as control group.Spontaneous activities during relaxation, mean duration and amplitude of motor unit potential (MUP), percentage of polyphasicity and variations during strong contraction were recorded and analyzed statistically.
There was significant difference in light contraction between MSA and non-MSA cases on both EAS-EMG and US-EMG (EAS-EMG, P<0.001; US-EMG, P=0.002).Meanwhile, strong contraction and percentage of polyphasicity showed significant differences between MSA and non-MSA cases on EAS-EMG only (strong contraction, P=0.016; percentage of polyphasicity, P=0.004).EAS-EMG showed more significant changes in neurogenic injury than US-EMG.
USEMG and EAS-EMG are valuable for the diagnosis of MSA.The differences of multiple parameters of EAS-EMG were more significant than those of US-EMG for MSA cases.US-EMG may serve as a supplement of EAS-EMG in case of restriction.
Efficacy and safety of ropinirole in the treatment of Parkinson disease: a multi-center, randomized, double-blind and bromocriptine-controlled trial
To explore the efficacy and safety of ropinirole in the treatment of Parkinson disease.
From November 2005 to April 2007, a total of 221 subjects from 7 hospitals of Beijing, Lanzhou and Wuhan participated in a 12-week multi-center, randomized, bromocriptine-controlled, double-blind, double-dummy and parallel-group trial.The efficacy of ropinirole was assessed with the unified Parkinson disease rating scale (UPDRS) score,"off"time according to the patient′s diary and the overall evolution of clinical efficacy.The safety was assessed on the basis of adverse events, blood pressure, pulse, laboratory measurement and electrocardiographic recordings.And the statistical analyses were performed with t, paired t, χ2 and covariance tests.
In the intent-to-treat population, the average UPDRSⅢ score decreased to (11±9) in ropinirole group and (11±10) in bromocriptine group while the UPDRSⅡ score decreased to (4±4) and (3±5) respectively at Week 12 versus baseline.It showed that ropinirole was noninferior to bromocriptine.The"off"time at Week 12[(3.0±1.2) h, (3.8±1.6) h] versus baseline[(4.2±2.0) h, (4.4±1.7) h] decreased (t=10.772, t=5.746, P=0.000) in ropinirole and bromocriptine groups.Ropinirole offered a better overall improvement rate (q=7.241, P=0.007).The adverse events occurring at a ratio of over 5% caused by ropinirole included orthostatic hypotension, nausea, dizziness, upper abdominal discomfort,insomnia and palpitation.No significant difference existed in the frequency of adverse events between two groups.
Ropinirole is both effective and safe in the treatment of Chinese patients with Parkinson disease.
Assessment of cognitive function,emotions and activities of daily living in patients with multiple system atrophy
To explore the cognitive function,emotional status and activities of daily living in patients with multiple system atrophy (MSA).
Thirty-two MSA patients and 38 healthy controls from October 2009 to November 2012 were recruited from our hospital.Their cognitive function,emotional status and activities of daily living were assessed.Cognitive function was assessed by Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE); emotional status by self-rating depression scale (SDS) and self-rating anxiety scale (SAS); daily living and activities by activities of daily living scale (ADL).Data analysis was performed with SPSS 19.0.And the results were presented as the mean±standard deviation.Comparison of means was performed with independent sample t test.And Pearson′s correlation test was used for correlation analysis.A Pvalue<0.05 was considered significant.
Mild or moderate cognitive impairment was documented in 71.9% of MSA patients.The scores of MoCA and MMSE in the MSA group were significantly lower than those in the control group.And the scores of ADL, SDSand SASin the MSA group were significantly higher than those in the control group (P<0.05).MoCA subitems such as space/executive function, attention, abstraction, language and delayed memory of the MSA group were significantly lower than those of the control group (P<0.05).A negative correlation existed between the scores of MoCA and MMSE with disease duration (P<0.01).There was a positive correlation between the scores of SDS and SAS with ADL and disease duration (P<0.05).And the relationship was significant between the scores of SDS and SAS (P<0.01).A positive correlation existed between scores of ADL with disease duration (P<0.05).
MSA patients have certain degrees of cognitive impairment, emotion disorders and impaired ADL.Cognitive impairment in MSA patients may be more common than previously.Furthermore, the clinical features of cognitive impairment in these patients may have some clinical values for references.
Comparative study on the diagnostic value of positron emission tomography and transcranial sonography in the diagnosis of Parkinson disease
To evaluate the consistency of dopamine transporter (DAT) positron emission tomography (PET) versus transcranial sonography (TCS) of Parkinson disease (PD) patients.
A total of 53 clinically diagnosed idopathic PD patients from Beijing Tiantan Hospital underwent 11C-CFT PET and transcranial sonography (TCS).Asymmetric reduced dopaminergic function was a positive result of PET while unilateral hyperechoic area larger than 0.2 cm2 a positive result of TCS.Kappa test was used to evaluate the consistency of two methods.Results Among them,36 patients (67.92%) were TCS positive while 17 patients (32.08%) TCS negative.There were 48 patients (90.57%) with positive PET whereas PET was negative for 5 patients (9.43%).TCS and PET were both positive in 33 patients (62.26%) while 2 (3.77%) yielded a double negative result.As compared with the PET results, the sensitivity, specificity, positive predictive value and negative predictive value of TCS were 68.75%, 40.00%, 91.67% and 11.76% respectively.For Kappa test, Kappa=0.042, P=0.690, P>0.05.It inferred a poor consistency.
TCS has a high predictive value for PET positive PD patients.For clinically diagnosed PD patients, a positive TCS result highly predicts PD without DAT-PET.However a negative TCS result can not rule out the possibility of PD.DAT-PET needs to be performed for further confirmation.
Short-segment fixation of thoracolumbar burst fractures using pedicle fixation at the level of fracture in patients with osteoporosis
To evaluate the curative effect of short-segment transpedicular fixation plus vertebra fracture fixation for thoracolumbar burst fractures in patients with osteoporosis.
The clinical data of thoracolumbar burst fractures in 46 patients with osteoporosis, single segment fracture and neurological intactness were analyzed retrospectively from January 2008 to January 2012.There were 20 males and 26 females with a mean age of 64.5 (56- 78) years.The mechanisms of injury were fall (n=20), traffic accident (n=12), high falling injury (n=8) and heavy pound injury (n=4).The involved vertebrae included T11 (n=5); T12 (n=17); L1 (n=21); L2 (n=3).Pedicle screw was inserted into injured vertebra and the height of collapsed vertebra fractures reduced with position and instrument.Visual analogue scale (VAS) and short form-36 scoring systems were used to evaluate pain level and quality of life.The height restoration and kyphotic correction rates of fracture level were measured radiologically.
All patients underwent surgery safely without severe complications.The average follow-up period was 20.5 (9-48) months.There was significant difference (t=20.057, P=0.000; t=24.287, P=0.000) in VAS score between last follow-up (3.09±1.01) and post-operation (2.35±1.02) versus pre-operation (7.22±1.05) respectively.And also there was significant difference (P<0.05) in SF-36 score between last follow-up (126.5±22.3) and post-operation (96.7±17.5).The Cobb angle was corrected to (5.6±1.9)° of post-operation and (7.8±3.3)° of last follow-up.The loss rate of vertebral was (4.8±5.2)% of post-operation and (7.6±2.9)% of last follow-up.There was no loosening or breakage of internal fixations.
The approach of short-segment transpedicular fixation plus vertebra fracture fixation is both safe and effective to maintain reduction and reduce the rate of correction loss and instrument failure.
Expression and significance of ACE2-Ang- (1-7) -Mas axis in endometrium of patients with polycystic ovary syndrome
To explore the expression of renin-angiotensin system component (ACEAngⅡ-AT1/AT2 and ACE2-Ang-(1-7) -Mas) in endometrium of polycystic ovary syndrome (PCOS) patients and normal controls.
Thirty cases of normal endometrium in proliferative and secretory phases respectively were selected for the protein levels of AngⅡ, AT1, AT2, ACE2, Ang-(1-7) and Mas through immunohistochemistry.And the specimens of proliferative endometrium from 15 PCOS patients and 15 normal controls respectively were prepared for the expressions of AT1, AT2, ACE2 and Mas m RNA through relative quantitative-polymerase chain reaction (RQ-PCR).The histological phases of endometria were confirmed by hematoxylin and eosin staining under microscope.
The expressions of AngⅡ, AT1R, AT2R, ACE2, Ang-(1-7) and Mas showed periodical changes in endometrium throughout normal menstrual cycles and shared a similar trend.The expression was more pronounced in epithelial cells than that in stromal cells while it was also more dramatic in secretory phase than proliferative phase; the m RNA expressions of AT1, AT2, ACE2 and MAS were higher in PCOS endometrium than those in normal controls.Statistically significant differences existed between two groups (P<0.01).
There is local existence of RAS in endometrium; increased expressions of AT1 mRNA, AT2 mRNA, ACE2 mRNA and Mas mRNA in endometrium of PCOS may influence endometrial development and play a role in the pathological process of PCOS.
Umbilicus metastasis in patients with epithelial ovarian cancer: clinical features of 21 patients
To analyze the clinical features, treatments and prognosis of patients with Sister Mary Joseph′s nodule of umbilicus (SMJN) from epithelial ovarian cancer (EOC) patients.
Among a total of 2642 pathologically diagnosed EOC cases, 21 cases with SMJN were histopathologically diagnosed and had an age range of 40- 66 years at Sun Yat-sen University Cancer Center between January 1991 and January 2011.Their clinical data were retrospectively analyzed.
The incidence of SMJN in EOC was 0.79%.The 1, 2 and 5-year survival rates were 61.8%, 26.8% and 9.5% respectively.The diagnosis was confirmed via local excision biopsy, fineneedle aspiration biopsy or gross pathological diagnosis.Univariate analysis showed that patients with progressive disease or relapsing with umbilical metastasis after treatment had worse prognosis than those diagnosed at pre-treatment (22 vs 6 months,P<0.01).Patients with suboptional cytoreductive surgery and/or less than 6 circles of chemotherapy or palliative treatment had worse prognosis than those with optional cytoreductive surgery during 6-8 circles of chemotherapy (21 vs 4 months).Multivarivate analysis showed that the time to diagnose and treatment regimen were independent predictors of survival (relative risk=41.28, P<0.01).
SMJN is a rare manifestation of EOC.Improving the diagnostic vigilance, optimal debulking surgery plus regular chemotherapy and other new individualized postoperative treatments may arrest the progression of EOC and prolong patient survival.
Clinical features and acid alpha-glucosidase gene mutation in 7 Chinese patients with glycogen storage disease typeⅡ
To explore the clinical features and acid alpha-glucosidase (GAA) gene mutations of Chinese patients with glycogen storage disease typeⅡ (GSDⅡ).
Seven patients with GSDⅡ were diagnosed by muscle pathology examination at Department of Neurology, Peking University First Hospital from 2003 to 2011.One patient with infant-onset presented development retardation, generalized muscle weakness, dyspnea, cardiomegaly and hepatomegaly.Six cases were of late-onset ranging from 1 to 29 years.Their main clinical features included progressive muscle weakness.Two patients developed respiratory insufficiency.Increased serum creatine kinase was detected in all of them.Electromyography studies showed myopathic (n=5) and neuropathic (n=1) changes.Muscle biopsies showed basophilic vacuoles in muscle fibers containing a large amountsof glycogen on electron microscopy.GAA gene mutation was detected by direct sequencing of polymerase chain reaction (PCR) product.Novel mutations were screened in 100 normal controls.
GAA gene mutations were found in all of them, including 10 point mutations and 1 frameshift deletion.Six mutations (p.P361L, p.P266S, p.R437C, p.R600C, p.W746S and p.W746) have been reported before.And five novel mutations (p.R168Q, p.R168P, p.E521V, p.R594H and c.827_845del) were found in this study.None of these novel mutations were found in 100 normal controls except for p.R168Q mutation in two normal controls.p.P361L and p.W746were detected in two unrelated GSDⅡpatients while other mutations were carried by only one patient.
In our study, we found several novel GAA mutations in Chinese patients with GSDⅡ.No hot spot mutation of GAA gene existed in our patient group.However, p.P266S, p.P361 L and p.R437C might be associated with late-onset GSDⅡ.
Comparison of the efficacy of different types of laryngeal mask airways in patients undergoing laparoscopic gynecological surgery
To compare the efficacy of laryngeal mask airway Supreme,ProSeal and I-gel in patients undergoing laparoscopic gynecological surgery.
From Jan 2010 to Sep 2012 in Beijing Hospital,approved by hospital ethics committee, ninety ASAⅠ or Ⅱ patients, aged 21-64 yr, weighing 45-90 kg,undergoing laparoscopic gynecological surgery,were randomized into 3 groups (n=30 each): LMA Supreme group (group S),LMA ProSeal group (group P) and LMA I-gel group (group I).Mallampatti test was performed before operation for each case.Anesthesia was induced with target-controlled infusion.LMA Supreme,LMA ProSeal and LMA I-gel were inserted in S,P and I groups respectively.A gastric tube was inserted through the drain tube of the LMA.The LMA placement time,the number of attempts of LMA insertion,the number of attempts of gastric tube placement,the airway sealing pressure,the parameters of ventilation,and complications (sore throat, odynophagia,hoarseness, regurgitation of gastric contents, LMA with adhesion of blood) were recorded.The fiberoptic laryngoscopy scores were assessed after LMA placement.The anesthesia time and recovery time were also recorded.
There was no significant difference in the anesthesia time,recovery time,fiberoptic bronchoscopy scores among the three groups (P>0.05).Parameters of ventilation in each group were normal.The success rates of LMA and gastric tube placement were 100% in each group.The airway sealing pressure in S,P and I groups were (25±5), (32±5), (30±6) cm H2O respectively,the airway sealing pressure was significantly higher in group P and group I, compare with group S (P<0.05).The LMA placement time in S, P and I groups were (8±4), (10±5), (8±3) s respectively,while the incidence of sore throat were 17%,20%,3%.The LMA placement time was significantly shorter and the incidence of sore throat was significantly lower in group I than in group P (P<0.05).
The three LMA can all be used effectively for gynecological laparoscopic surgery.LMA I-gel and LMA ProSeal can provide higher airway sealing pressure.LMA I-gel provides adequate ventilation during operation with fewer complications.
Surgical treatment of pulmomary tuberculosis complicated with aspergilloma
To investigate the surgical indications of pulmonary tuberculosis complicated with aspergilloma,and to reduce postoperative complications.
From 1993 to 2010,a total of 51surgically treated patients in pulmonary tuberculosis complicated with aspergilloma were analyzed retrospectively.The common surgical procedure performed was lobectomy (60.8%), followed by segmentectomy (15.7%), pneumonectomy (9.8%), wedge resection (9.8%).
Postoperative non-fatal complications occurred in all patients, the complications (13 cases) included postoperativeatelectasis (7.8%), bleeding (5.9%),bronchopleural fistula (5.9%), cardiacarrhythmia and heart failure (2.0%),incisional infection (2.0%).
Surgical treatment of pulmonary tuberculosis complicated with aspergilloma is the most effective treatment| pulmonary resection is the treatment of choice when indicated.
Three-dimensional flow perfusion culture enhances proliferation of human fetal osteoblasts in large scaffold with controlled architecture
To demonstrate the feasibility and benefits of custom designed perfusion bioreactor in conjunction with well-defined three-dimensional (3D) environment for enhanced proliferation and homogeneous distribution of human fetal osteoblasts in large scaffold in vitro.
Large-scaleβ-tricalcium phosphate (β-TCP) scaffolds with tightly controlled architectures were fabricated.And a custom designed perfusion bioreactor was developed.Human fetal osteoblasts were seeded onto the scaffolds, cultured for up to 16 days in static or flow perfusion conditions.At Days 4, 8 and 16 post-incubation, the proliferation and distribution of osteoblasts were determined by daily D-glucose consumption, cell viability (methyl thiazolyl tetrazolium (MTT) assay), histological evaluation and scanning electron microcopy (SEM).Sphere like structures observed in the SEM images were assessed by energy dispersive X-ray (EDX) analysis.
In both static and perfusion cultures, the daily D-glucose consumption increased with prolonged time.The daily Dglucose consumption was significantly higher in the perfusion culture than that in static culture (P<0.05).The increased cell viability with time during the culture was similar to the daily D-glucose consumption under both conditions.There was much greater cell viability under flow perfusion culture compared to static culture (P<0.05).Flow perfused constructs demonstrated improved cell proliferation and a homogeneous layer composed of cells and extracellular matrix in channels throughout the whole scaffold.However, the cells were biased to periphery in scaffolds culture statically.Sphere like structures present in the matrix were identified as calcium phosphate nodules via EDX analysis.
Flow perfusion culture plus well-defined 3D interconnected channel environments enhances the proliferation and improve the distribution of human fetal osteoblasts in large scaffolds.Scaffolds with controlled architecture may be a potential tool of studying the fluid flow configuration and cell behavior inside scaffold in details.And human fetal osteoblasts can be used as a cell source in large bone graft research.
Microcirculational changes in elderly septic patients
To explore the changes of sublingual microcirculation in elderly patients with severe sepsis/septic shock.
Twenty-three patients with sepsis, 10 patients without sepsis and 10 healthy elderly patients were enrolled.Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging.And the 28-day mortality rates of all septic patients were recorded.
Compared with the healthy group, all elderly patients had significant sublingual microcirculational dysfunctions.Compared with the severe septic and nonseptic patients, perfused vessel density (PDV), proportion of perfused vessels (PPV) and microvascular flow index (MFI) of septic shocks were significantly lower.Compared with the severe septic patients, PDV, PPV and MFI instead of lactate and MAP of septic shocks were significantly lower from Day 1 to Day 3.The values of PDV, PPV, MFI and lactate but not MAP of the surviving septic patients were significantly higher than those of the deceased ones.
The elderly patients with septic shock have severe sublingual microcirculatory alterations.And these abnormalities are more marked in septic shock patients.Nonsurvivors showed more severe alterations than survivors.Microcirculatory alterations may be measured to guide the therapy.
Virus spectrum features of adult influenza-like fever in outpatients
To analyze the results of detection on respiratory virus of influenza-like illness (ILI) in Beijing from June 2010 to February 2012 and understand the virus spectrum of adult influenza-like fever.
A total of 502 swabs were collected and 279 throat swabs tested for 12 respiratory viruses with multiplex reverse transcription-polymerase chain reaction (RT-PCR).And 413 swabs were tested for p H1N1 by virus isolation influenza viruses.And the data were statistically analyzed.
One or two viruses were detected in 26.9% (75/279) of the samples.Influenza A virus (FLU-A) accounted for 85.3% of positive samples and 22.9% (64/279) of ILI tested.The positive rate of other viruses was less than 3.0%.The positive rates among the following subtypes were:2.7% (11/413) for p H1N1, 2.4% (10/413) for H3 and 6.5% (27/413) for FLU-B.FLU-A was the predominant virus during the 2010-2011 influenza season and the positive rate peaked in January 2011 in Beijing and north China.FLU-B was the primary virus during the 2011-2012 influenza season and the positive rate peaked in January and February 2012.There was a significant reduction in the incidence of ILI in 2010 and 2011 when compared with 2009.During the 2009-2012 influenza seasons, the incidence peaked in December 2009, January 2011 and January and February 2012 in Beijing.
Exposure to pH1N1 had no impact on typical influenza seasonal peaks.Influenza virus was the predominant virus of adult influenza-like fever cases after the pandemic period of influenza A (H1N1) 2009 and the positive rate peaked in January and February during the 2009-2012 influenza seasons.
Relationship between Golgi apparatus and cell migration direction in vivo and in vitro
To explore the relationship between Golgi apparatus and the direction of tumor cell migration in vivo and in vitro.
Cell migration assays were conducted with rat C6 glioma cells, human U251 and SNB19 glioma cells respectively.Then immunofluorescence was used to detect the position of Golgi apparatus in migrating cells.The percentage of cells with Golgi apparatus facing towards wound edge was calculated.Cell pseudopodium was stained with TRITCphalloidin and the relationship between Golgi apparatus and pseudopodium detected.Immunohistochemistry was used to reveal the Golgi apparatus in tumor tissue samples.And the percentage of cells with Golgi apparatus facing opposite to the necrotic zones was calculated.
In cells located at wound edge, the Golgi apparatus was found facing towards the wound in the vast majority of cells (C6 83%±6%, U251 80%±7%, SNB19 82%±6%).In U251 and SNB19 cells, the golgi apparatus was located in the same direction with cellular pseudopodium.Immunohistochemical staining showed that in cells located around the necrotic zone, the Golgi apparatus faced opposite to the necrotic zones in most cells (rat tissue samples 80%±7%, human tissue samples 82%±6%).
The Golgi apparatus is closely correlated with cell migration and it may be considered as a direction indicator of cell migration.And it provides an important index for the study of tumor cell invasion both in vivo and in vitro.
Role of CX3CR1/ERK5 pathway in spinal microglia for the development of neuropathic pain
To explore the role of spinal microglial CX3CR1/ERK5 pathway in the development of neuropathic pain.
The model of spinal nerve ligation (SNL) was established by ligating the L5 spinal nerve with 6-0 silk thread in male Sprague Dawley rats.The expression of activated ERK5 (p-ERK5) was examined by immunohistochemistry test.To detect the role of ERK5 in neuropathic pain, PWT and PWL were measured after an intrathecal knockdown of ERK5.For determining the regulating effect of CX3CL1/CX3CR1 on the activity of microglial ERK5, CX3CR1 was blocked by an intrathecal injection of anti-rat CX3CR1 antibody and the activity of spinal ERK5 tested.Then whether an intrathecal knockdown of ERK5 could reverse the effect of CX3CL1 on pain hypersensitivity and microglia activation was investigated.
ERK5 was activated in spinal microglia after SNL compared to the sham group (61.75±11.52 vs 2.2±0.12; 58.01±10.45 vs 1.1±0.11).The knockdown of ERK5 by an intrathecal injection of antisense oligonucleotides suppressed the mechanical (15.42±3.46 vs 22.7±3.2g; 13.6±2.9 vs 21.4±4.1 g) and thermal hyperalgesia (13.48±2.0) vs (18.0±3.7) s; (11.6±2.3) vs (17.7±1.4) s induced by nerve injury.The blockage of CX3CR1, a receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL (30±9) vs (58±12); (50±12) vs (36±4)(P<0.05).In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation.
CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through ERK5.
Clinical application of a new titanium clip applier in transsphenoidal surgery
To explore the efficacy and safety of a new titanium clip applier in tramssphenoidal surgery for the A specially devised surgery instrument was developed and effectively applied in the management of intercavernous sinus hemorrhage and cerebrospinal fluid (CSF) leakage in transsphenoidal surgery.
A total of 34 consecutive patients with pituiary adenoma underwent transsphenoidal surgery via a new deep pistol-shaped clip applier versus titanium clip.It was 21 cm long with a rectangular forepart.All patients were evaluated clinically and radiologically at 24 months and magnetic resonance imaging (MRI) was performed at Months 3- 18 postoperation.
The application of such a new clip applier was effective.No operation was terminated due to ineffective hemorrhagic control or CSF leakage management.None of them had clinical symptoms of delayed hemorrhage, postoperative CSF leakage or related complications.Postoperative imaging studies revealed no significant evidence of clip artifact.
The technique of hemostasis and leakage clogging with such a new clip applier is safer, faster and more reliable than its conventional counterpart in achieving dural closure and intercavernous sinus hemostasis.
Potential of induced pluripotent stem cells in peripheral arterial disease
Research progress of Lewy body dementia
Research progress of magnetic resonance diagnosis of cerebral microhemorrhage
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