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*

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

Objective:To explore the trans-membrane signaling mechanism of interleukin-6 (IL-6)-induced osteogenic differentiation and calcification of human umbilical artery smooth muscle cells (HUASMCs).Methods:HUASMCs were primarily cultured in vitro and were stimulated with IL-6, IL-6+solutable IL-6 receptor (sIL-6R), IL-6+sIL-6R+solutable gp130 (sgp130), or vehicle (blank control). Alizarin red and Von Kossa staining were used for detecting cell calcification, Western blot was used to test the protein expression of tissue-nonspecific alkaline phosphatase (TNAP), osteopontin (OPN), bone morphogenetic protein-2 (BMP-2) and Runt related transcription factor 2 (Runx2), and immunofluorescence was used to examine the mIL-6R expression of HUASMCs. The comparison of measurement date between the two groups was conducted by t-test. The comparison of measurement date between multiple groups was conducted by one-way analysis of variance (ANOVA). Results:The intensity severity of calcification stain was IL-6+sIL-6R group >IL-6+sIL-6R+sgp130 group>IL-6 group=blank control. After stimulated for 12 hours, the TNAP expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.44±0.08), (0.52±0.14), (0.84±0.16) and (0.55±0.10) respectively ( F=290.96, P<0.001). After stimulated for 3 days, the OPN expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.61±0.84), (0.95±0.16), (1.65±0.24) and (0.99±0.10) respectively ( F=507.72, P<0.001). After stimulated for 12 hours, the BMP-2 expression in blank control, IL-6 group, IL-6+sIL-6R group, IL-6+sIL-6R+sgp130 group were (0.77±0.05), (1.69±0.16), (2.81±0.26) and (0.57±0.12) respectively ( F=959.09, P<0.001). After stimulated for 3 days, the Runx2 expression in blank control, IL-6 group, IL-6+sIL-6R group,IL-6+sIL-6R+sgp130 group were (0.57±0.03) , (0.92±0.10), (1.31±0.13) and (0.66±0.06) respectively ( F=1141.27, P<0.001). Comparing with Jurkat cells (positive control) and CEM cells (negative control), HUASMCs limited expressed mIL-6R. Conclusion:IL-6 may induce HUASMCs osteogenic differentiation and calcification mainly via the sIL-6R-mediated trans-signaling pathway.

Objective:To analyze the relationship between self-disclosure, self-efficacy and medical coping modes in adolescent depression, and explore the mediating effect of self-efficacy between self-disclosure and medical coping modes.Methods:Using the convenience sampling method, a total of 403 adolescents with depression in a tertiary psychiatric hospital in Beijing were recruited from March 2020 to March 2021. The data of general information questionnaire, distress disclosure index scale, medical coping modes questionnaire and general self-efficacy scale were collected.SPSS 26.0 software was used to analyze the correlation between self-disclosure, self-efficacy and medical coping modes of adolescent patients with depression, and Stata 13.1 software was used to analyze the mediating effect of self-efficacy between self-disclosure and medical coping modes.Results:The scores of dimension of the medical coping modes of adolescent depression patients were(16.90±3.84) for facing, (16.34±2.88) for yielding, (12.48±4.31) for avoiding, (30.47±9.91) for self-disclosure and (19.63±6.54) for self-efficacy, respectively. Self-disclosure and self-efficacy were positively correlated with facing of medical coping modes ( r=0.301, 0.327, both P<0.01), and negatively correlated with yielding of medical coping modes ( r=-0.465, -0.487, both P<0.01). Self-disclosure was negatively correlated with avoidance of medical coping modes ( r=-0.118, P=0.018). The direct effect of self-efficacy on medical coping modes was 0.103, and the total effect was 0.365, and the mediating effect accounted for 28.22%. Conclusion:Self-efficacy partially mediates between self-disclosure and medical coping modes in adolescents with depression.

Objective:Comparing with the external fixator technique, investigate the clinical effect of fixator-assisted plating technique for treatment distal femoral valgus deformity in adolescent.Methods:A retrospective analysis of the relevant data of 22 patients (25 limbs) with acute correction of distal femoral valgus deformities from July 2015 to June 2019, according to the difference of the final fixation, they were divided two groups. The fixator-assisted plating group, including 8 patients (9 limbs), 5 boys and 3 girls, 5 left and 2 right, 1 bilateral, the physis were closed in 4 cases and opened in 4 cases, age 14.04±1.99 years (11.7-18 years). The external fixator group, including 14 patients (16 limbs), 6 boys and 8 girls, 8 left and 4 right, 2 bilateral, the physis were closed in 9 cases and opened in 5 cases, age 13.33±1.88 years (10.1-16.5 years). Measuring the mechanical axis deviation (MAD) and the mechanical lateral distal femur angle (mLDFA) in full length standing AP view X-ray of the lower limb pre and post operation. Recording the changed of limb length discrepancy (LLD) before and after surgery and the knee range of motion at 6 weeks, 3 months, 6 months and the last follow up post operation. The Kolcaba comfort status scale was used to evaluate the comfort of two groups at 2 weeks, 6 weeks, 3 months, 6 months and the last follow up. Meanwhile recorded the healing time of osteotomy sites and the complications.Results:The difference in general information between the two groups was not statistically significant. The fixator-assisted plating group followed up mean 26 months (range, 12-40 months), the healing time were 4.00±0.66 months, the mLDFA mean 73.33°±4.12° before surgery and 87.89°±1.69° after surgery and there was significant difference ( t=10.582, P<0.05). The external fixator group followed up mean 36 months (range, 22-42 months), the healing time were 4.00±0.66 months, the mLDFA mean 73.31°±3.95° before surgery and 87.31°±1.54° after surgery and there was significant difference ( t=14.118, P<0.05). The MAD were in the normal range in all patients after surgery, and there were no significant difference about healing time of the osteotomy sites and postoperative mLDFA between the two groups ( t=1.514, P=0.150; t=0.845, P=0.411). Comparing with the knee function, the fixator-assisted plating group was better at 6 weeks, 3 months, 6 months after surgery but there was no difference at the last follow up. Also, the fixator-assisted plating group felt more comfortable at 2 weeks, 6 weeks, 3 months, 6 months and there was no difference at the last follow up. All the patients with external fixator have mild pin sites infection and there were no obvious complications in patients with plate. Conclusion:The fixator-assisted plating technique can accurately correct the valgus deformity with satisfactory healing of the osteotomy in distal femoral compare with the external fixator technique, but the patients feel more comfortable and the knee joint function recovers faster and no risk of pin site infection, the clinical results was satisfactory with fewer complication.

Objective:To analyze the risk factors of avascular necrosis (AVN) after closed reduction and spcia casting in treating developmental dysplaisa of the hip (DDH).Methods:The patients with DDH who received closed reduction in our department from January 2016 to December 2017 were retrospectively reviewed. The inclusion criteria included aged at reduction ≥6 months, achieving successful reduction, having complete data with more than 2 years follow-up. A total of 48 cases with 54 hips were included in the present study. Among them, there were 2 males and 46 females, 41 unilateral hips and 13 bilateral hips. The mean age at closed reduction was 16.4±3.8 months (range 6-24 months). The mean follow-up duration was 2.9±1.8 years (range 2.3-4.1 years). Closed reduction was conducted under general anesthesia followed with a spcia cast immobilization. The abduction angle of the cast was recorded. The stability of reduction was evaluated by Ramsey safety zone. The maximum abduction and re-dislocation abduction were recorded. The quality of reduction was evaluated by the medial gap and femoral head coverage on intraoperative arthrography and post-reduction MRI. AVN was diagnosed according to Salter criteria. The risk factors of AVN were analyzed by univariate and binary logistic regression analysis.Results:AVN occurred in 12 hips (22.2%) of 54 hips. International Hip Dysplasia Institute (IHDI) grade and the difference between maximum abduction and cast abduction (Max-Cast abduction) were related to the occurrence of AVN in univariate analysis. The incidence of AVN in hips of IHDI grade 4 (42.9%, 9/21) was significantly higher than that in hips of IHDI grade 3 (9.7%, 3/31) (χ 2=6.007, P=0.018). However, the hips of IHDI grade 3 and 2 (0%, 0/2) presented a similar incidence of AVN (χ 2=0.000, P=1.000). The Max-Cast abduction was -0.7°±5.9° in the AVN group and 6.1°±7.6° in the AVN group ( t=2.125, P=0.038). Finally, IHDI grade ( OR=8.256, P=0.015) and Max-Cast abduction ( OR=0.832, P=0.047) were both independent factors of AVN in multivariate analysis. Conclusion:Most of the hips with AVN are IHDI grade 4 after closed reduction for DDH. The abduction angle in a spica cast could not be significantly related to the occurrence of AVN. However, the risk of AVN might be increased when the cast abduction is close to or beyond the maximum abduction. Safe abduction in the cast should be 5 to 10 degrees less than maximum abduction at least.

To evaluate the surgical technique and clinical effect of applying Flow-through flap pedicled with superficial palmar branch of radial artery for bridging finger replantation complex defect of soft tissue and vessel. Methods From February, 2013 to March, 2018, 9 cases of severed fingers composited defect of soft tissue and vessel were treated with Flow-through flap pedicled with superficial palmar branch of radial artery.The flap was designed from the proximal end of rasceta and the donor sites were sutured directly. The size of flaps was 3.0 cm ×1.5 cm-4.0 cm×2.2 cm. The superficial branch of the radial artery in the flap was used to bridge the finger artery. And the vein of proximal and distal ends in the finger was bridged by the subcutaneous vein. The proper palmar digi-tal nerve defect was bridged by palm skin graft of median nerve. The appearance, feeling and joint function of fingers was followed-up regularly after operation. Results All transfering flaps survived and all cases were followed-up for 7 to 33 months. The donor sites got primary healing with straight scars. The appearance and texture of the flaps were satisfactory. Two-point discrimination ranged from 8 to 11 mm. The pain sensation, warmth sensation and touch sen-sation of the flaps got better. And the appearance and functions of severed fingers recovered well. Conclusion The Flow-through flap pedicled with superficial palmar branch of radial artery is easy to harvest and anastomose, which is masked and a small incision for the donor site. It is an ideal method for bridging severed fingers and repairing of fin-ger wound.

Objective To investigate the correlation between serum interleukin-6 (IL-6) to albumin ratio (IAR) at admission and early outcome of patients with acute noncardioembolic ischemic stroke.Methods From January 2013 to May 2015,patients with acute noncardioembolic ischemic stroke admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University were enrolled retrospectively.Three months after onset,the clinical outcome were assessed by the modified Rankin scale (mRS),0-2 was good outcome,and ＞ 2 was poor outcome.The baseline clinical data,laboratory tests,and IAR in both groups were compared.Multivariate logistic regression analysis was used to determine the independent risk factors affecting early outcomes.Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of IAR for early outcome.Results A total of 236 patients were enrolled in the study,including good outcome in 143 (60.6％) and poor outcome in 93 (39.4％).Univariate analysis showed that age (62.99 ± 11.34 years vs.59.62 ± 11.83 years;t =-2.176,P=0.031),serum IL-6 (37.56 ± 3.82 ng/L vs.34.82 ± 3.13 ng/L;t =-6.016,P ＜ 0.001),IAR (1.02 ± 0.08 vs.0.93 ± 0.07;t =-9.474,P＜0.001),and the proportions of patients with severe stroke (6.5％ vs.0％;x2 =8.142,P =0.012) and combined CHD (30.1％ vs.18.2％;x2 =4.542,P =0.033) of the poor outcome group were significantly higher than those of the good outcome group.Multivariate logistic regression analysis showed that high IAR at admission was an independent risk factor for early poor outcome (odds ratio,5.192,95％ confidence interval 3.283-8.213;P ＜0.001).ROC curve analysis showed the optimal cut-off value of IAR predicting for early outcome was 1.00,and the area under the ROC curve was 0.807 (95％ confidence interval 0.748 to 0.860).The sensitivity was 62.4％,the specificity was 88.1％,the positive predictive value was 69.2％,the negative predictive value was 79.3％,and the accuracy was 75.4％.Conclusions High serum IAR at admission was an independent risk factor for early poor outcome in patients with acute noncardioembolic ischemic stroke.It had a certain predictive value for the outcomes.

Objective To explore the surgical technique of applying the pedicle composite tissue flap based on superficial palmar branch of the radial artery to repair the soft tissue defect of thumb and evaluate the clinical ef-fect. Methods From February,2013 to March, 2016, 5 cases of the soft tissue and tendon defect of thumb were treated with the pedicle composite tissue flap based on superficial palmar branch of the radial artery. The flap was de-signed at wrist not exceeding the wrist rasceta and the donor site was sutured directly. The size of the harvested flaps was between 3.0 cm ×2.2 cm to 4.2 cm ×3.2 cm, and the sensation of thumb or the flap was reconstructed via median nerve cutaneous branch. The Extensor pollicislongus muscle tendon defect was repaired via palm tendon carried by composite tissue flap. Postoperative follow-up was done termly. Results All transfering flaps survived and all cases were followed-up for 4 to 11 months. The donor site got primary healing with a linear scar. The appearance and tex-ture of the flap was satisfactory. The two-point discrimination ranged from 8 to 11 mm. The appearance of thumb re-covered well and the digit joint had a good motion. Conclusion The pedicle composite tissue flap based on superfi-cial palmar branch of the radial artery is easy to harvest and its vascular anatomy is constant, which is masked and a small incision for the donor site. When necessary, palm tendon or median nerve cutaneous branch can be contained in the flap to form a composite transplant. It is an ideal method for repair of thumb soft tissue defect.

Paraquat is a commonly used herbicide,which can cause acute poisoning due to misusage or suicide.The mortality of acute paraquat poisoning is high,the prognosis is poor,and there is no specific an-tidote for the poisoning.Most scholars believe that early blood purification is the first choice for the treatment of acute paraquat poisoning.However,there is not a unified standard about what kind of blood purification methods and the specific parameters should be taken for the different periods of paraquat poisoning.