Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective:To analyze clinical phenotypes and pathogenic mutations of a patient with classic tuberous sclerosis complex.Methods:Clinical data was collected from a patient with classic tuberous sclerosis complex. Next-generation sequencing was performed to screen pathogenic gene variants, and Sanger sequencing to verify the mutations. Minigene plasmids were constructed and transfected into the human renal epithelial cell line 293T, and RNA was extracted for transcriptional analysis.Results:The patient clinically presented with recurrent epileptic seizures, facial angiofibroma, periungual fibroma, pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and multiple osteosclerosis. Next-generation sequencing revealed a suspected pathogenic variant in the TSC2 gene in the patient. Sanger sequencing identified a heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene in the patient, but not in his parents or 100 unrelated healthy controls. Moreover, this mutation had not been previously reported. The minigene experiment showed changed mRNA sequence of the TSC2 gene in this patient with loss of the authentic splice site in exon 4 and insertion of a 74-bp intron, which shifted the splice site 90 bp downstream (r.336delins336+16_336+90) .Conclusion:The novel heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene can lead to aberrant splicing, and may contribute to tuberous sclerosis complex in this patient.

OBJECTIVE: To explore the genetic basis for a patient diagnosed with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect potential variant, and the result was verified by Sanger sequencing. RESULTS: The patient was found to harbor a heterozygous c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene. The same variant was not found in his unaffected parents and 100 unrelated healthy controls. Based on the American College of Medical Genetics and Genomics guidelines, the variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The novel c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene probably underlay the TSC in this patient.
Genomics ; Heterozygote ; Humans ; Mutation ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

A systematic characterization of the similarities and differences among different methods for detecting structural brain abnormalities in schizophrenia, such as voxel-based morphometry (VBM), tensor-based morphometry (TBM), and projection-based thickness (PBT), is important for understanding the brain pathology in schizophrenia and for developing effective biomarkers for a diagnosis of schizophrenia. However, such studies are still lacking. Here, we performed VBM, TBM, and PBT analyses on T1-weighted brain MR images acquired from 116 patients with schizophrenia and 116 healthy controls. We found that, although all methods detected wide-spread structural changes, different methods captured different information - only 10.35% of the grey matter changes in cortex were detected by all three methods, and VBM only detected 11.36% of the white matter changes detected by TBM. Further, pattern classification between patients and controls revealed that combining different measures improved the classification accuracy (81.9%), indicating that fusion of different structural measures serves as a better neuroimaging marker for the objective diagnosis of schizophrenia.

OBJECTIVE: To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy. METHODS: Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing. RESULTS: The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c.2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents. CONCLUSION The recurrent frame-shifting mutation c.2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.
Diagnostic Errors ; Epilepsy ; diagnosis ; genetics ; Female ; Frameshift Mutation ; Humans ; Tuberous Sclerosis ; diagnosis ; genetics ; Tuberous Sclerosis Complex 1 Protein ; genetics ; Tuberous Sclerosis Complex 2 Protein ; genetics

Objective: To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy. Methods: Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing. Results: The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c. 2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents. Conclusion The recurrent frame-shifting mutation c. 2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

OBJECTIVETo compare the effects between penetration acupuncture at Baxie (EX-UE 9) combined with rehabilitation and simple rehabilitation for swelling hand in post-stroke shoulder-hand syndrome.

METHODSSixty patients were randomly assigned into an observation group and a control group,30 cases in each one. Penetration acupuncture at Baxie (EX-UE 9) combined with rehabilitation were used in the observation group,and the acupoints were the affected Baxie (EX-UE 9) and Wailaogong (EX-UE 8). Simple rehabilitation was used in the control group. All the treatment was given for 3 weeks,5 days a week with 2 days at the interval,once a day. The swelling degree and motor function of the affected hand were assessed before and after treatment in the two groups. Also,the effects were compared.

RESULTSThe swelling and motor function scores after treatment were improved compared with those before treatment in the two groups(all<0.01),with better effects in the observation group(both<0.01). The total effective rate was 93.3%(28/30) in the observation group,which was better than 73.3%(22/30) in the control group(<0.01).

CONCLUSIONSPenetration acupuncture at Baxie (EX-UE 9) combined with rehabilitation can effectively and timely alleviate the swelling hand and motor function of post-stroke shoulder-hand syndrome,which are better than simple rehabilitation.

Objective To identify Chinese character writing related cortex (WRC) and its relationship with hand motor cortical areas. Methods Ten native Chinese-speaking, right-hand volunteers were recruited in the study. NTMS mapping was conducted during picture naming task. The WRC were mapped based on nTMS-induced impairment of Chinese character writing. The extent and area of WRC was calculated. The right-hand motor representations were mapped while motor-evoked potentials were produced under nTMS stimulation. EMG data and coordinates of positive stimulus were recorded. The relationship between WRC and hand motor cortex (HMC) was analyzed on the basis of area comparison and distance calculation. Results The cortical areas related to Chinese character writing were mapped successfully in all subjects by nTMS. WRC was primarily centered in left posterior middle frontal gyrus (pMFG) (86%,55/64). The mean WRC area (161.03 mm2 ±62.58mm2) was significantly smaller than the mean HMC area (589.50 mm2±227.34mm2) (P<0.001). The WRC and HMC were not conjoined or overlapped in the dominant hemisphere. The distance between those two was 12.58mm±2.71mm. Conclusions NTMS can provide reliable assistance in mapping WRC areas. The WRC is relatively fixed and centralized in pMFG but is not overlapped with the HMC.

OBJECTIVE: This experiment aims to determine the diagnostic value of diffusion-weighted imaging (DWI) in the differentiation of axillary inflammatory lymph nodes from metastatic lymph nodes in rabbit models in comparison with conventional magnetic resonance imaging (MRI). MATERIALS AND METHODS: Conventional MRI and DWI were performed at 4 weeks after successful inoculation into the forty female New Zealand white rabbits' mammary glands. The size-based and signal-intensity-based criteria and the relative apparent diffusion coefficient (rADC) value were compared between the axillary inflammatory lymph nodes and metastatic lymph nodes, with histopathological findings as the reference standard. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the aforementioned criteria and rADC value in differentiating the axillary inflammatory lymph nodes from metastatic lymph nodes. RESULTS: Thirty-two axillary inflammatory lymph nodes and 46 metastatic ones were successfully isolated and taken into pathological analysis. The differences of the aforementioned criteria between the two groups were not statistically significant (p > 0.05). However, the rADC value of the inflammatory lymph nodes (0.9 +/- 0.14) was higher than that of metastatic ones (0.7 +/- 0.18), with significant difference (p = 0.016). When the rADC value was chosen as 0.80, the area under the ROC curve is greater than all other criteria, and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for differentiating two groups were 86.2%, 79.3%, 81.2%, 84.2%, and 85.6%, respectively. CONCLUSION: Diffusion-weighted imaging is a promising new technique for differentiating axillary inflammatory lymph nodes from metastatic lymph nodes. Compared with routine magnetic resonance sequences, DWI could provide more useful physiological and functional information for diagnosis.
Animals ; Axilla ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; Female ; Inflammation/pathology ; Lymphatic Metastasis/*pathology ; Magnetic Resonance Imaging/*methods ; Mammary Neoplasms, Experimental/*pathology ; ROC Curve ; Rabbits ; Sensitivity and Specificity