Erratum: Author correction to 'Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis in vivo' [Acta Pharmaceutica Sinica B 11 (2021) 3950-3965].

[This corrects the article DOI: 10.1016/j.apsb.2021.07.027.].

Maternal nicotine intoxication before pregnancy induces depressive- and anxiety-like behaviors as well as cognitive deficits in male offspring and correlates with neurobiological changes.

INTRODUCTION: Maternal nicotine use has been suggested to affect the behavior of children and is linked to changes in neurological systems; however, the specific mechanism is yet to be understood. METHODS: Mice were used to establish a maternal nicotine intoxication model. At postnatal day 60 (adolescent stage), male offspring were tested for behavioral tasks including sucrose preference, open field, elevated plus maze, light/dark box, object recognition, Morris water maze (MWM), and forced swimming. Enzyme-linked immunoassays were used to measure plasma concentrations of neurotransmitters including norepinephrine, dopamine, serotonin, and corticosterone. Serotonin transporter (Sert), brain-derived neurotrophic factor (Bdnf), cAMP response element binding protein (Creb), and phosphorylated (p)Creb mRNA levels were measured using quantitative real-time polymerase chain reaction. RESULTS: Male offspring of nicotine-intoxicated dams had significantly reduced sucrose preference, mobility time in the forced swimming test, and locomotor and exploratory activities. Offspring in the maternal nicotine intoxication group showed increased signs of depressive- and anxiety-like behavior. Recognition memory in the MWM was compromised in these animals. The hippocampal and prefrontal cortical regions showed significant changes in Bdnf, pCreb, and Sert gene expression, whereas CREB mRNA levels were unaffected. Moreover, compared to the controls, neurogenesis and neuronal viability were also reduced in these animals. CONCLUSION: Prenatal nicotine exposure might affect the hypothalamic-pituitary-adrenal axis and reduce neurogenesis, potentially leading to depressive-like behaviors and cognitive deficiencies in male offspring.

Solvent Mediating the in Situ Self-Assembly of Polysaccharides for 3D Printing Biomimetic Tissue Scaffolds.

Intensively studied 3D printing technology is frequently hindered by the effective printable ink preparation method. Herein, we propose an elegant and gentle solvent consumption strategy to slowly disrupt the thermodynamic stability of the biopolymer (polysaccharide: cellulose, chitin, and chitosan) solution to slightly induce the molecule chains to in situ self-assemble into nanostructures for regulating the rheological properties, eventually achieving the acceptable printability. The polysaccharides are dissolved in the alkali/urea solvent. The weak Lewis acid fumed silica (as solvent mediator) is used to (i) slowly and partially consume the alkali/urea solvent to induce the polysaccharide chains to self-assemble into nanofibers to form a percolating network in a limited scale without leading to gelation and (ii) act as the support to increase the solution modulus, for achieving superior printability and scaffold design flexibility. As a demonstration, the resulting polysaccharide scaffolds with biomimetic nanofibrous structures exhibit superior performances in both the cell-free and cell-loaded bone tissue engineering strategies, showing the potential in tissue engineering. Moreover, the fumed silica could be completely removed by alkali treatment without defecting the nanofibrous structure, showing the potential in various applications. We anticipate our solvent-mediated 3D printing ink preparation concept could be used to fabricate other polymeric facile inks and for widespread applications in diverse fields.

Biocompatible Chitin Hydrogel Incorporated with PEDOT Nanoparticles for Peripheral Nerve Repair.

The nerve guidance conduit (NGC) is a promising clinical strategy for regenerating the critical-sized peripheral nerve injury. In this study, the polysaccharide chitin is used to fabricate the hydrogel film for inducing the impaired sciatic nerve regeneration through incorporating the conductive poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs) and modifying with cell adhesive tetrapeptide Cys-Arg-Gly-Asp (CRGD) (ChT-PEDOT-p). The partial deacetylation process of chitin for exposing the amino groups is performed to (i) improve the electrostatic interaction between chitin and the negatively charged PEDOT for enhancing the composite hydrogel strength and (ii) offer the active sites for peptide modification. The as-prepared hydrogel remarkably promotes the in vitro RSC-96 cell adhesion and proliferation, as well as the Schwann cell activity-related gene S100, NF-200, and myelin basic protein (MBP) expression. Function of gastrocnemius muscle and thickness of myelinated axon in chitin/PEDOT groups are analogous to the autograft in 10 mm rat sciatic nerve defect. Immunofluorescence, immunohistochemistry, western blotting, and toluidine blue staining analyses on the regenerated sciatic nerve explain that the attachment and proliferation enhancement of Schwann cells and angiogenesis are the vital factors for the chitin/PEDOT composite to facilitate the nerve regeneration. This work provides an applicable chitin-based NGC material for accelerating the peripheral nerve restoration.

Limb-Salvage Outcomes of Arterial Repair Beyond Time Limit at Different Lower-Extremity Injury Sites.

BACKGROUND The purpose of this study was to analyze the outcomes of revascularization exceeding 12 h after arterial injury at different sites of the lower extremity. MATERIAL AND METHODS From January 2009 to April 2017, 58 patients with 58 lower-limb arterial injuries who underwent revascularization over 12 h after trauma were included in our study. Outcomes measured, including mortality, amputation, complications, and other parameters (gait, length discrepancy, the range of movement of the knee and ankle joint, and muscle wasting) were analyzed. RESULTS External iliac artery injury (EIAI) or femoral artery injury (FAI) was affected in 4 patients, superficial femoral artery injury (SFAI) in 18, and popliteal artery injury (PAI) (including proximal gastrocnemius muscle vascular (PGMV) and proximal gastrocnemius muscle vascular [PGMV]) in 36. The median time of arterial injury was 72 h (interquartile range, 59.5). No mortality was found. Amputations were performed in 16 patients due to non-viable limbs, progressing infection, or muscle necrosis. All patients were followed up (median, 52 months; interquartile range, 5.5). Of the 42 limb-salvage patients, most had a limp, muscle wasting, or ankle and knee dysfunctions, and 26 patients with knee or ankle dysfunction underwent secondary surgery. CONCLUSIONS Although limited recanalization of blood vessels may lead to limb complications or amputations over time, the high success rate of limb salvage still merits the surgeon's best efforts.

Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis in vivo.

With the understanding of microRNA (miRNA or miR) functions in tumor initiation, progression, and metastasis, efforts are underway to develop new miRNA-based therapies. Very recently, we demonstrated effectiveness of a novel humanized bioengineered miR-124-3p prodrug in controlling spontaneous lung metastasis in mouse models. This study was to investigate the molecular and cellular mechanisms by which miR-124-3p controls tumor metastasis. Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3p in A549 cells, which were assembled into multiple cellular components critical for metastatic potential. Among them, plectin (PLEC) was verified as a new direct target for miR-124-3p that links cytoskeleton components and junctions. In miR-124-3p-treated lung cancer and osteosarcoma cells, protein levels of vimentin, talin 1 (TLN1), integrin beta-1 (ITGB1), IQ motif containing GTPase activating protein 1 (IQGAP1), cadherin 2 or N-cadherin (CDH2), and junctional adhesion molecule A (F11R or JAMA or JAM1) decreased, causing remodeling of cytoskeletons and disruption of cell-cell junctions. Furthermore, miR-124-3p sharply suppressed the formation of focal adhesion plaques, leading to reduced cell adhesion capacity. Additionally, efficacy and safety of biologic miR-124-3p therapy was established in an aggressive experimental metastasis mouse model in vivo. These results connect miR-124-3p-PLEC signaling to other elements in the control of cytoskeleton, cell junctions, and adhesion essential for cancer cell invasion and extravasation towards metastasis, and support the promise of miR-124 therapy.

The Masquelet technique combined with the muscle flap for use in emergency management of acute Gustilo type III trauma of the lower limb with segmental bone loss:Case series.

BACKGROUND: Gustilo-Anderson type III traumas have been described as high-energy injuries with severe bone defects and extensive soft tissue damage, which remain a challenging entity, due to an inherent risk of infection, nonunion and even amputation. The emergency management of such severe trauma presents additional difficulties. Our study attempts to retrospectively evaluate the Masquelet technique combined with the muscle flap for the management of Gustilo type III trauma of the lower limb with segmental bone loss in emergencies and assess key points of success in this technique. MATERIAL AND METHODS: From June 2014 to December 2017, 17 patients of Gustilo type IIIA/B/C trauma of lower limb with segmental bone loss, were recruited for our studies. All the cases experienced thorough debridement, stabilization of fracture and antibiotic-impregnated cement spacer insertion. When necessary, muscle flap surgeries were performed immediately. After wound healing, cement spacers were removed, and cancellous bone was filled to repair bone defects. Procedures were performed by two experienced orthopedic surgeons. RESULTS: Among the patients studied, retrograde translocations of the medial head of the gastrocnemius were performed in 5 cases, medial hemimuscular flaps of soleus in 3 cases, and medial head of the gastrocnemius combined with medial hemimuscular flaps of soleus in 4 cases. One patient developed a necrotic soleus flap and was treated with the cross-leg flap. Using a mean 28.2 months of follow-up, results were analyzed radiologically and clinically. Failures (include infection and nonunion) were not noted. And all the patients returned to full weight bearing without pain. According to the Paley fracture healing score, 15 patients showed excellent results and 2 patients displayed good results regarding bone outcomes. When considering functional outcomes, 14 patients exhibited excellent results and 3 patients displayed good results. CONCLUSIONS: The muscle flap is synergistic with the Masquelet technique in the emergency management of severe complex fractures. The combination of both techniques in emergency surgery demonstrates an alternative option for the treatment of acute Gustilo type III trauma of the lower limb with segmental bone loss, which can effectively prevent bone infection and amputation. We also demonstrate that firm fixation is key to the Masquelet technique.

[Treatment of severe distal humeral bone defects with three-dimensional printing technology].

Objective: To explore the application of three-dimensional (3D) printing technology in precise and individualized surgical treatment of severe distal humeral bone defect. Methods: Five patients with severe distal humeral bone defects were treated with customized 3D printing prostheses between December 2010 and December 2015. There were 4 males and 1 female, with an age of 23-57 years (mean, 35 years); and the length of the bone defect was 5-12 cm (mean, 8 cm). The cause of injury was mechanical injury in 2 cases and strangulation in 3 cases. All of them were the open fracture of Gustilo type Ⅲ. There were 2 cases of radial fracture, 1 case of cubital nerve injury, and 3 cases of radial nerve injury. The time from injury to one-stage operation was 6-18 hours (mean, 10 hours). The operation time, intraoperative blood loss, and intraoperative fluoroscopy were recorded. During follow-up, the anteroposterior and lateral X-ray films of the elbow joints were performed to identify whether there was prosthesis loosening; Mayo Elbow Performance Score (MEPS) and upper extremity Enneking score were used to evaluate limb function. Results: The operation time was 140-190 minutes (mean, 165 minutes). The intraoperative blood loss was 310-490 mL (mean, 415 mL). The intraoperative fluoroscopy was 1-3 times (mean, 1.6 times). Five patients were followed up 14-38 months (mean, 21 months). The wound exudate occurred in 1 case and cured after anti-inflammatory local dressing change; the subcutaneous hematoma occurred in 1 case, and improved after color Doppler ultrasound guided puncture and drainage. The MEPS scores and the Enneking scores were all significantly improved when compared with preoperative ones ( P<0.05). Except MEPS score between 6 and 12 months after operation had no significant difference ( P>0.05), there were significant differences in MEPS scores and Enneking scores between the other time points ( P<0.05). During the follow-up, no prosthetic loosening or joint dislocation occurred. Conclusion: 3D printing technology can achieve personalized treatment of severe distal humeral bone defects, obtain relatively good elbow joint function, and has less postoperative complications and satisfactory effectiveness.

[Clinical observation of osteotomy and fusion for the treatment of severe rigid equinus deformity].

OBJECTIVE: To explore clinical efficacy of osteotomy and fusion in treating severe rigid equinus deformity. METHODS: From April 2010 to October 2015, 13 patients(16 feet) with severe rigid equinus deformity were treated with osteotomy and fusion by hollow screw, including 6 males and 7 females aged from 39 to 62 years old with an average of(49.6±5.3) years old;the courses of diseases ranged from 5 to 27 years with an average of (9.0±4.8) years. Six patients (9 feet) were treated with osteotomy and fusion for three joints, 4 patients(4 feet) were treated with osteotomy and fusion for four joints, and 3 patients (3 feet) were treated with osteotomy and fusion for tibiotalar and calcaneal-talar joints. All patients manifested as foot pain, heel could not touch floor and walking before operation. Postoperative complications were observed, AOFAS score were applied to evaluate clinical effect. RESULTS: Thirteen patients were followed up from 18 to 24 months with an average of 20 months. Only one patient occurred local skin necrosis after operation and healed by dressing change and anti-infective therapy. All feet obtained fracture healing, the time ranged from 12 to 16 weeks with an average of 13.2 weeks. AOFAS score were improved from 11.85±10.66 before operation to 81.38±3.69 after operation, and had significant difference(t=-25.67, P<0.05);15 feet good and 1 foot moderate. CONCLUSIONS: Tibiotalar and calcaneal-talar joint fusion, osteotomy and fusion for three and four joints could treat severe rigid equinus deformity according to patients' individual and could obtain satisfied clinical effects.

Genetic variation in angiotensin converting-enzyme affects the white matter integrity and cognitive function of amnestic mild cognitive impairment patients.

Angiotensin-converting enzyme (ACE) gene has been implicated in amnestic mild cognitive impairment (aMCI). Most human genetic studies have focused on ACE insertion (I)/deletion (D) polymorphism and yielded conflicting results. In this work, we evaluated the relationships between cognitive function, serum ACE level, brain white matter (WM) integrity, and ACE I/D polymorphism in 48 patients with aMCI and 36 well matched control subjects from south China. In aMCI patients, D allele frequency was higher (D/I ratio=0.51:0.49) than that of the control subjects (D/I ratio=0.43:0.57); however, the difference was not statistically significant (p>0.05). The D carriers in aMCI subjects performed significantly poorer on auditory-verbal learning test (AVLT) -delayed recall than the I homozygous group (p=0.035). These carriers had higher serum ACE level than the I homozygous carriers of aMCI (p=0.037). In the aMCI group, D carriers showed significantly lower fractional anisotropy (FA) values in the left middle frontal gyrus, left anterior cingulate, right gyrus parahippocampalis, right inferior parietal lobule, and bilateral anterior central gyrus than the I homozygotes carriers. However, no significant difference was observed in FA values between I homozygotes and D carriers in the control subjects. The ACE D allele in aMCI patients may increase the risk of cognitive impairment. A high serum ACE level possibly plays an important role in the incidence of aMCI.

[Intramedullary nail combined with auxiliary plate and bone cement in treatment of pathologic fracture of extremities caused by metastatic tumors].

Objective: To explore the application of intramedullary nail fixation combined with auxiliary plate and bone cement in the palliative treatment of pathologic fracture of extremities caused by metastatic tumors. Methods: Clinical data of 11 cases with pathologic fracture of extremities caused by metastatic tumors between April 2015 and October 2016 were retrospectively analyzed. All the patients were treated by intramedullary nail fixation combined with auxiliary plate and bone cement. There were 6 males and 5 females with an age of 54-72 years (mean, 62.9 years). The disease duration was 1.0-1.5 months. Of the 11 patients, 4 metastatic tumors were diagnosed at humerus, 6 at femur, and 1 at tibia, respectively. And the tumor infiltration length ranged from 3.3 to 5.6 cm (mean, 4.6 cm), the depth could reach the bilayer of limb bones. All the patients had suffered the limbs pain and incapability of physical movement. The preoperative visual analogue scale (VAS) score was 6.36±1.03, and the Karnofsky Performance Status (KPS) score was 42.73±10.09. The operation time, intraoperative blood loss, and postoperative complications were recorded. The VAS score, KPS score, and Musculoskeletal Tumor Society (MSTS) score were used to evaluate the effectiveness at 3 months after operation. Results: The operation time was 1.1-1.8 hours (mean, 1.5 hours), the intraoperative blood loss was 102.5-211.3 mL (mean, 135.6 mL). Postoperative limb incisions healed well without infection, necrosis, and delayed healing or other complications. All the patients were followed up 7-10 months (mean, 8.2 months). At 3 months after operation, the functions of limbs recovered. The VAS score decreased to 0.82±0.75 and the KPS score increased to 85.45±5.22, both showing significant difference when compared with preoperative ones ( t=35.218, P=0.000; t=-18.470, P=0.000); and the MSTS score was 23.91±2.47. At last follow-up, the anteroposterior and lateral X-ray films showed that all the limbs healing well and no breakage of intramedullary nail and steel plate, or loosening in bone cement, limb shortening, malalignment, or other complications occurred. Conclusion: In treating metastatic tumors of extremities, the combination of intramedullary nail fixation with auxiliary plate and bone cement will contribute to an invariable length and fixed location for limbs, resulting in biomechanical stability for skeleton. Under this premise, the tumor lesions can be eliminated and pathological pains be relieved, so as to improve patients' life quality.

Association of angiotensin-converting enzyme functional gene I/D polymorphism with amnestic mild cognitive impairment.

The relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and serum ACE activity, as well as amnestic mild cognitive impairment (aMCI), was investigated. The study recruited 90 aMCI patients and 90 matched healthy controls. All subjects underwent an extensive assessment of cognitive function. The ACE gene I/D genotype was determined by polymerase chain reaction. Serum ACE activity was measured using a spectrophotometric technique. The scores obtained by the aMCI patients on the neuropsychological tests were significantly lower than those of the control subjects (all p<0.01). The genotype (χ(2)=11.510) and allele (χ(2)=6.945) frequencies of the ACE gene were significantly different between the aMCI and the control groups (all p<0.01). The DD genotype (23%) and D-allele (57%) frequencies in the aMCI patients were higher than those in the controls (16% vs. 43%). ACE genotype was correlated with delayed recall in Auditory Verbal Memory Test, delayed recall in Complex Figure Test, Category Fluency Test, and Symbol Digit Modalities Test in all subjects, in which the carriers of the DD and DI genotypes obtained lower scores than those of the II genotype (p<0.05). A significant difference in the serum ACE level was observed among the three genotypes (DD>DI>II) in both the aMCI and the control groups (all p<0.01). D-allele may be a genetic risk factor for the development of aMCI to Alzheimer's disease. A high serum ACE level possibly plays an important role in the incidence of aMCI.

ACE I/D polymorphism affects cognitive function and gray-matter volume in amnestic mild cognitive impairment.

To characterize the correlates of cognitive function, serum concentrations of angiotensin converting enzyme (ACE) and brain structure with the ACE insertion or deletion (I/D) polymorphism were analyzed in subjects with amnestic-mild cognitive impairment (aMCI). A group of 48 subjects meeting criteria for aMCI and 36 age-matched control subjects were assessed using a comprehensive battery of standardized neuropsychological tests and magnetic resonance imaging (MRI). The ACE gene's I/D polymorphism was analyzed by means of PCR, and serum ACE concentrations were measured using ultraviolet spectrophotometry. Genotype effects on neuropsychological domains and MRI gray matter volume (GMV) measurements (optimized voxel-based morphometry) were examined using general linear models. The D carriers among the aMCI subjects performed significantly worse on AVLT-delayed recall compared to the I homozygous group. The D carriers had higher serum ACE concentrations than did the I homozygous carriers, though this difference only reached statistical significance in the aMCI group. Compared with the I homozygous carriers, in the aMCI group, D carriers showed smaller GMV of the bilateral middle frontal gyrus, right cuneus, right precentral gyrus, right medial frontal gyrus, right superior frontal gyrus, and left postcentral gyrus. However, there was no significant difference in GMV between I homozygous and D carriers in the normal control group. The study suggests that ACE genotype has considerable effect on the cognitive performance of aMCI subjects, particularly episodic memory, serum activity of ACE, and the structure of specified brain regions. The ACE D allele may be a genetic risk factor for greater atrophy of gray matter in aMCI.

Alteration of resting brain function by genetic variation in angiotensin converting enzyme in amnestic-type mild cognitive impairment of Chinese Han.

Using a cross-sectional case-control study of amnestic-mild cognitive impairment (aMCI), we characterised the relationships among cognitive function, serum levels of angiotensin converting enzyme (ACE), brain activity, and ACE insertion or deletion (I/D) polymorphism. Forty-eight patients with aMCI and 36 well-matched normal controls were assessed by a comprehensive battery of standardized neuropsychological tests. In addition, regional homogeneity (ReHo) approaches were used to analyze blood oxygen level-dependent functional magnetic resonance imaging data on the resting state in all subjects, and genotyping of the serum ACE was measured in aMCI patients. The D carriers with aMCI patients were found to have markedly higher serum ACE levels than I homozygote carriers. Importantly, compared with the carried I homozygote group of patients with aMCI, the D carriers of aMCI patients were significantly impaired in the AVLT-delayed recall and had decreased ReHo over the bilateral precuneus, left middle occipital gyrus, right inferior parietal lobe, and right angular gyrus, whilst increased ReHo was found mainly in the left medial frontal gyrus, right paracentral lobe, and right anterior cingulate cortex. The findings indicated that ACE genotype was associated with episodic memory, serum levels of ACE, and resting-state brain activity in aMCI patients, and the findings of cognitive function and brain activity further suggests that the ACE D allele may have a specific role in semantic memory dysfunction and brain activity in aMCI.

Association study of the decreased serum BDNF concentrations in amnestic mild cognitive impairment and the Val66Met polymorphism in Chinese Han.

OBJECTIVE: Experimental and clinical data suggested that brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is characterized by declined cognitive function and has a high probability of evolving into AD. The aim of this study was to investigate serum BDNF concentrations in aMCI patients and determine whether there is an association of the BDNF gene Val66Met polymorphism with aMCI, cognitive function, and serum BDNF. METHOD: Between April 2005 and January 2006, the present study recruited 99 aMCI patients who met diagnostic criteria for MCI proposed by the Mayo Clinic Alzheimer's Disease Research Center and 99 matched healthy controls from a population-based sample. All subjects underwent extensive assessment of cognitive function, measurement of serum BDNF by an enzyme-linked immunosorbent assay, and genotyping of the BDNF gene Val66Met polymorphism. RESULTS: The serum concentrations of BDNF in aMCI patients (median [interquartile range] = 4.37 [2.35-6.40] ng/mL) were significantly lower than those of healthy controls (4.98 [3.50-7.33] ng/mL) (z = -2.449, p = .014). There were significant positive correlations between serum BDNF and scores on delayed recall in the Auditory Verbal Learning Test, which reflects episodic memory (r = 0.264, p = .008). No significant differences were found for either the genotype or allele distribution of BDNF Val66Met polymorphism between aMCI patients and control subjects. The BDNF Val66Met polymorphism was not associated with serum BDNF or cognitive function in aMCI patients. CONCLUSIONS: This study suggests that reduced BDNF levels may play a role in the pathophysiology of aMCI, and the BDNF gene Val66Met polymorphism may not be an important factor in susceptibility to aMCI.

[Cognitive function, serum BDNF levels and BDNF gene Val66Met polymorphism in amnestic mild cognitive impairment].

OBJECTIVE: To investigate the relationship between serum brain-derived neurotrophic factor, concentrations and BDNF gene Val66Met polymorphism and amnestic mild cognitive impairment (aMCI), and neuropsychological characteristics. METHODS: Ninety-nine aMCI patients and 99 matched normal controls were recruited for the study. Multi-dimension neuropsychologic tests were used to extensively assess the cognitive function, an enzyme-linked immunosorbent assay was applied to measure serum BDNF concentrations, and polymerase chain reaction-restriction fragment length polymorphism was used to analyse BDNF gene Val66Met polymorphism in the subjects. RESULTS: The scores of neuropsychologic tests in aMCI patients were significantly lower than those in the normal controls (all P<0.001), with the largest impairment on delayed recall of the auditory verbal memory test (AVMT) which reflect verbal episodic memory. The serum concentrations of BDNF in aMCI patients (median: 4.37 microg/L) were significantly lower than those of the normal controls (median: 4.98 microg/L) (z=-2.449, P=0.014). There was positive correlation between the serum concentrations of BDNF and the scores on delayed recall of AVMT (r=0.264, P=0.008). No significant differences were found for the genotype and allele distribution of BDNF Val66Met polymorphism between aMCI patients and the normal controls. BDNF Val66Met polymorphism was not associated with serum BDNF concentrations and cognitive assessment scores in aMCI patients (P>0.05). CONCLUSION: aMCI is characterized by episodic memory impairment. Decreased BDNF concentrations may play a role in the pathophysiology of aMCI, and BDNF gene Val66Met polymorphism may not be an important genetic factor in susceptibility to aMCI.