Objective To identify key acoustic features associated with the progression of Alzheimer's disease(AD)through voice analysis combined with machine learning and feature selection techniques,thereby constructing classification models that serve as candidate tools for the early screening of AD.Methods Voice samples from AD,mild cognitive impairment(MCI)and healthy(HC)elderly individuals were obtained from the NCMMSC2021 AD voice dataset.The voice samples underwent data preprocessing,followed by feature extraction from the eGeMAPS feature set via the OpenSmile toolkit.Classification models were obtained utilizing random forest and support vector machine(SVM)algorithms.Significance testing and feature importance ranking were conducted using Python,and the further selection of the optimal features was performed through sequential forward selection(SFS).The classification performance before and after feature selection was compared and evaluated using accuracy and the area under the receiver operating characteristic curve(AUC).Results The significant acoustic features in the classification models primarily derived from spectral slope,formant,fundamental frequency,and loudness.The optimal classification performance was achieved with the SVM model following SFS feature selection,with recognition accuracies of 0.926(AUC=0.974)for AD/MCI group,0.875(AUC=0.956)for AD/HC group,and 0.879(AUC=0.904)for MCI/HC group.Conclusion SVM model performs better than random forest model,and the use of SFS for feature selection can effectively enhance model performance.Voice analysis has the potential to serve as a valuable supplementary tool for the rapid AD assessment and screening.

Objective To identify key acoustic features associated with the progression of Alzheimer's disease(AD)through voice analysis combined with machine learning and feature selection techniques,thereby constructing classification models that serve as candidate tools for the early screening of AD.Methods Voice samples from AD,mild cognitive impairment(MCI)and healthy(HC)elderly individuals were obtained from the NCMMSC2021 AD voice dataset.The voice samples underwent data preprocessing,followed by feature extraction from the eGeMAPS feature set via the OpenSmile toolkit.Classification models were obtained utilizing random forest and support vector machine(SVM)algorithms.Significance testing and feature importance ranking were conducted using Python,and the further selection of the optimal features was performed through sequential forward selection(SFS).The classification performance before and after feature selection was compared and evaluated using accuracy and the area under the receiver operating characteristic curve(AUC).Results The significant acoustic features in the classification models primarily derived from spectral slope,formant,fundamental frequency,and loudness.The optimal classification performance was achieved with the SVM model following SFS feature selection,with recognition accuracies of 0.926(AUC=0.974)for AD/MCI group,0.875(AUC=0.956)for AD/HC group,and 0.879(AUC=0.904)for MCI/HC group.Conclusion SVM model performs better than random forest model,and the use of SFS for feature selection can effectively enhance model performance.Voice analysis has the potential to serve as a valuable supplementary tool for the rapid AD assessment and screening.

Gastric cancer is one of the major diseases threatening human health, with a high incidence and a low early diagnostic rate. There are many bottlenecks encountered during its treatment. Consequently, improving the early diagnostic rate and exploring new therapeutic targets are currently urgent challenges that need to be addressed. Telomerase is undetectable in normal tissues, but it exhibits high specificity and sensitivity in most cancers and has a definite correlation with prognosis. It may serve as a serum tumor marker and prognostic indicator. Human telomerase reverse transcriptase (hTERT) gene polymorphism can regulate the susceptibility of people to gastric cancer, and affect the occurrence, development, proliferation and apoptosis of gastric cancer through its target gene. Substances such as resistin, visfatin, G-quadruplex and methylenedioxyaniline can affect the occurrence and development of gastric cancer by regulating telomerase expression. The mechanism by which hTERT regulates tumor invasion and metastasis is currently unclear, so elucidating its mechanism is of great significance.This paper will review the research progress of this mechanism in recent years.

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.

Objective:To evaluate the efficacy of oral levothyroxine on abortion rate and preterm birth rate in pregnant women with thyroid autoimmunity (TAI) and normal thyroid function.Methods:The relevant studies of oral levothyroxine tablets in the treatment of TAI pregnant women were systematically searched in Pubmed, Cochrane, CBM, CNKI, VIP and Wanfang databases. The retrieval period was established until August 2020. Two researchers independently screened the literatures, extracted the data and evaluated the risk of bias in the included study. Meta-analysis was performed using Revman5.3 software.Results:1) Totally six eligible studies were all randomized controlled studies, involving 1427 patients. 2) Compared with control group, the meta-analysis suggests oral levothyroxine tablets cannot effectively reduce the preterm delivery rate and the abortion rate. 3) Further subgroup analysis of the data according to the natural pregnancy group and assisted reproduction group found that oral levothyroxine tablets in natural pregnancy women with TAI can effectively reduce the preterm delivery rate ( RR=0.54, 95% CI=0.31-0.95, P=0.03), but not reduce the abortion rate ( RR=0.86, 95% CI=0.69-1.06, P=0.15). However, oral levothyroxine tablets cannot reduce the abortion rate for TAI women conceived by reproductive technology ( RR=0.80, 95% CI=0.47-1.36, P=0.41). Conclusion:Oral levothyroxine tablets can effectively reduce the premature delivery rate of TAI women who are naturally pregnant, but it is not beneficial to reduce the abortion rate. There is only one study on TAI women who are pregnant with reproductive technology, so it is impossible to evaluate whether this population can benefit from taking levothyroxine tablets. In view of the above results, it is recommended that the two groups of patients be managed separately.

Objective:To investigate the clinical features and prognosis of acute necrotizing encephalopathy (ANE) in children.Methods:The clinical data and follow-up information of 41 pediatric patients with ANE treated in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from January 2014 to September 2019 were retrospectively reviewed.Results:The 41 patients included 23 males and 18 females with the onset age of (4.4±3.2) years.The main prodromal symptoms were gastrointestinal (20/41 cases, 48.8%) and respiratory infections (19/41 cases, 46.3%). Acute encephalopathy progressed rapidly following the prodromal infection [29 cases (70.7%) ≤2 days], and patients had clinical manifestations of coma (32/41 cases, 78.0%), convulsion (32/41 cases, 78.0%), multiple organ dysfunction (27/41 cases, 65.9%), shock and disseminated intravascular coagulation were rarely occured, and 28 cases (68.3%) were admitted to intensive care unit for treatment.Brain magnetic resonance imaging (MRI) showed lesion involving thalamus (41/41 cases, 100.0%), periventricular white matter (34/41 cases, 82.9%), brainstem (31/41 cases, 75.6%), basal ganglia (26/41 cases, 63.4%), cerebral cortex and subcortex (20/41 cases, 48.8%) and cerebellum (18/41 cases, 43.9%). The common presentations on the apparent diffusion coefficient mapping of brain MRI were " tricolor pattern" or " bicolor pattern" of the thalamus.During follow-up (≥ 6 months), MRI showed that hemorrhage, cystic degeneration and atrophy changed dynamically with the progression of ANE.All cases were treated with glucocorticoids, 38 cases(92.7%) with intravenous immune globulin.Seven cases (17.1%) were died and the 34 survivors had different degrees of neurological dysfunction.Conclusions:ANE in children is a distinctive type of clinicoradiologic syndrome with rapid progression and various presentations.Brain MRI has typical imaging characteristics and dynamically indicates the progression of this disease.The treatment options are still limited, the prognosis is poor and the survivors are often with neurological dysfunction.

Objective:To investigate the expression of Per2 mRNA, HDAC1 mRNA and E-cadherin mRNA in esophageal cancer cells and their significance.Methods:The experimental study was conducted. Human normal esophageal epithelial cells as the control group and human esophageal cancer cell line KYSE-150 cells as the experimental group were cultured in vitro to logarithmic growth stage. Observation indicators: (1) the proliferation of cells; (2) the migration and invasion of cells; (3) the expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA in cells of initial physiological state; (4) the expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA after cells were treated with Per2-agonists or inhibitors; (5) the expression of Per2 mRNA and E-cadherin mRNA after cells were treated with HDAC1 inhibitors. Measurement data with normal distribution were represented as Mean± SD, the t test was used for comparison within groups and the t test or ANCOVA were used for comparison between groups. Results:(1) The proliferation of cells: the cell proliferation of the experimental group and control group were 0.90%±0.14% and 0.52%±0.08%, with a significant difference between the two groups ( t=5.166, P<0.05). (2) The migration and invasion of cells: the numbers of cell migration and invasion for the experimental group were 173±41 and 86±27, versus 50±15 and 21±9 for the control group, with significant differences between the two groups ( t=6.274, 5.153, P<0.05). (3) The expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA in cells of initial physiological state: the expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA in cells of initial physiological state for the experimental group was 11.7±2.7, 20.4±6.6, and 12.4±2.5, respectively, versus 2.4±0.5, 8.5±2.2, and 27.3±4.5 for the control group, with significant differences between the two groups ( t=5.782, 2.982, -5.034, P<0.05). (4) The expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA after cells were treated with Per2-agonists or inhibitors: after cells were treated with Per2-agonists, the expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA were 13.1±2.2, 22.4±6.2, 16.6±4.2 for the experimental group, and 9.9±3.1, 18.4±5.6, 15.3±2.3 for the control group, respectively. There was no significant difference in the expression of Per2 mRNA, HDAC1 mRNA, or E-cadherin mRNA of the experimental group between cells being treated with and without Per2-agonists ( t=-4.300, 10.087, -4.187, P>0.05). There were significant differences in the expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA of the control group between cells being treated with and without Per2-agonists ( t=-4.846, 3.501, 9.294, P<0.05). There was no significant difference in the expression of Per2 mRNA or E-cadherin mRNA between the experimental group and control group after cells were treated with Per2-agonists ( F=1.000, 7.582, P>0.05), while there was a significant difference in the expression of HDAC1 mRNA between the two groups ( F=1.724, P<0.05). After cells were treated with Per2-inhibitors, the expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA were 4.1±1.7, 7.5±2.2, 22.8±4.2 for the experimental group, and 3.1±0.9, 9.3±3.2, 28.4±5.8 for the control group, respectively. There were significant differences in the expression of Per2 mRNA, HDAC1 mRNA, and E-cadherin mRNA of the experimental group between cells being treated with and without Per2-inhibitors ( t=12.124, 5.105, -10.245, P<0.05). There was no significant difference in the expression of Per2 mRNA, HDAC1 mRNA, or E-cadherin mRNA of the control group between cells being treated with and without Per2-inhibitors ( t=-2.815, 1.568, -1.439, P>0.05). There were significant differences in the expression of Per2 mRNA and E-cadherin mRNA after cells were treated with Per2-inhibitors between the experimental group and control group ( F=22.965, 82.134, P<0.05), while there was no significant difference in the expressions of HDAC1 mRNA between the two groups ( F=6.416, P>0.05). (5) The expression of Per2 mRNA and E-cadherin mRNA after cells were treated with HDAC1 inhibitors: after cells were treated with HDAC1 inhibitors, the expression of Per2 mRNA and E-cadherin mRNA were 13.4±3.5, 24.2±3.4 for the experimental group, and 3.1±1.2, 26.8±5.2 for the control group, respectively. There was no significant difference in the expression of Per2 mRNA of the experimental group between cells being treated with and without HDAC1-inhibitors ( t=-3.959, P>0.05). There was a significant difference in the expression of E-cadherin mRNA of the experimental group between cells being treated with and without HDAC1-inhibitors ( t=-21.977, P<0.05). There was no significant difference in the expression of Per2 mRNA or E-cadherin mRNA of the control group between cells being treated with and without HDAC1-inhibitors ( t=-1.440, 1.058, P>0.05). After cells were treated with HDAC1-inhibitors, there was no significant difference in the expressions of Per2 mRNA between the experimental group and control group ( F=2.004, P>0.05), while there was a significant difference in the expression of E-cadherin mRNA between the two groups ( F=325.800, P<0.05). Conclusions:Human esophageal cancer cells have an elevated expression of Per2 mRNA and HDAC1 mRNA, and a reduced expression of E-cadherin mRNA. The overexpression of Per2 mRNA may activate the expression of downstream targeting protein HDAC1, and inhibit the expression of cell surface E-cadherin mRNA.

Objective:To analyze the imaging features of acute necrotizing encephalopathy of childhood (ANEC), and try to investigate its potential clinical value.Methods:The clinical and imaging findings of 22 children from Wuhan Children′s Hospital diagnosed with ANEC were retrospective analyzed, from January 2013 to October 2018. All children were presented with hyperpyrexia and rapidly developed into rapid neurological deterioration after prodromic infection. In the initial imaging examination, all patients underwent head MRI, and 6 cases underwent additional head CT. During MRI follow-up, 4 cases were lost, 6 cases were followed up only once (<14 days), and 12 cases were followed up 1 to 2 times at short-term and 1 to 4 times at long-term (>14 days).The presence of hemorrhage and encephalomalacia in thalamus, brainstem, white matter and basal ganglia was carefully investigated throughout the follow-up.Results:For the imaging manifestations of ANEC, bilateral thalamus were involved in all children. Other symmetrical lesions included white matter (14 cases), basal ganglia (15 cases), brainstem (16 cases), cerebellum (9 cases), corpus callosum (2 cases) and hippocampus (1 case). There were 3 children with asymmetric lesions, which were found in white matter (2 cases) and cerebellum (1 case).In the acute phase, the most typical head MRI showed "tricolor pattern"(high signal intensity in the center with surrounding low-signal, and hyperintense signals in the periphery of thalamus) or "bicolor pattern"(low signal in the central thalamus with surrounding hyperintense signals) of the thalamus on the apparent diffusion coefficient (ADC) imaging. Hemorrhage and encephalomalacia on MRI may suggest poor clinical outcome.Conclusions:ANEC is a rapid progressive encephalopathy with typical imaging features. Hemorrhage and encephalomalacia on MRI may be associated with poor prognosis.

Objective: To investigate the impact of intensified maintenance therapy on the prognosis of children and adolescents with advanced lymphoblastic lymphoma (LBL) . Methods: Retrospective analysis on the treatment results of children and adolescents with stage Ⅲ and stage Ⅳ LBL who underwent BFM-NHL-90/-95 regimen without prophylactic radiotherapy. The intensified therapy group included the patients admitted from 1998 to 2005, while others were classified as the non-intensified therapy group. Patients in the intensified therapy group were intravenously treated with "etoposide phosphate plus cytrarabine" and high-dose methotrexate alternately per 2.5-3 months in addition to the oral chemotherapy with 6-mercaptopurine and methotrexate during the maintenance phase. Results: A total of 187 LBL patients were enrolled. The rates of 5-year event free survival were (76.9 ± 5.8) % and (77.9 ± 4.3) % (χ²=0.249, P=0.617) respectively, in the intensified therapy (n=52) and the non-intensified therapy groups (n=135) , while the rates of 5-year overall survival of them were (78.8 ± 5.7) % and (79.8±4.1) % (χ²=0.353, P=0.552) , respectively. Stratified by stage, immunological type as well as risk stratification, the rates of long-term survival were similar between the two groups. During the maintenance phase, the rates of grade Ⅲ and Ⅳ myelosuppression in the intensified therapy and the non-intensified maintenance groups were 55.8% and 18.5%, respectively (χ²=25.363, P<0.05) . Conclusion Intensified maintenance therapy failed to improve the prognosis of patients with advanced LBL.