Objective To understand the application effect of early screening scale and behavioral intervention effect in children with autism spectrum disorder (ASD). Methods A total of 348 children with suspected ASD were selected and evaluated using the Modified Checklist for Autism in Toddlers (M-CHAT) and Autism Behavior Checklist (ABC). The evaluation results were compared with those from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Children enrolled were given Early start Denver model (ESDM) intervention. The evaluation results of Gesell Developmental Scale and Autism Treatment Evaluation Checklist (ATEC) scores were compared before and after intervention. Results The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating ASD in children aged 1-3 years were 89.53%, 90.70%, 89.92% and 0.78. The corresponding values of ABC were 78.49%, 81.40%, 79.46% and 0.56. The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating children aged >3-6 years were 87.30%, 77.78%, 84.44% and 0.64. The corresponding values of ABC were 85.71%, 77.78%, 83.33% and 0.62. The sensitivity and accuracy of M-CHAT were higher than ABC for evaluating ASD in children aged 1-3 years (P<0.05). There were no significant differences in sensitivity, specificity and accuracy between M-CHAT and ABC for evaluating ASD in children aged 3-6 years (P>0.05). After intervention, development quotients (DQ) of personal-social aspects, adaptability, language, gross motor, and fine motor of children with ASD were higher than those before intervention (P<0.05). ATEC scores for language, behavior, sensation, and social contact of children with ASD were lower than those before intervention (P<0.05). Conclusion M-CHAT and ABC both can be used for early screening of ASD in children, especially M-CHAT. Early behavioral intervention can effectively improve the condition and developmental level of children with ASD.

Objective:To explore the recurrence pattern and prognosis of cervical cancer after radical chemoradiotherapy.Methods:Clinical and follow-up data of 1 359 patients with stage Ⅰ-ⅣA (International Federation of Gynecology and Obstetrics 2009 staging) who received radical radiotherapy in Zhejiang Cancer Hospital from August 2011 to December 2017 were retrospectively analyzed. The survival and prognostic factors of 249 patients with recurrence / metastasis with detailed data were analyzed. The primary endpoint was post-recurrence / metastasis survival time. Kaplan-Meier method was used to calculate the survival rate, log-rank test was used for single factor analysis, and Cox model was used for multi-factor analysis.Results:The distant metastasis rate of 249 patients was 77.5%, and the local recurrence rate was 36.9%. According to the location of metastasis and recurrence, 56 cases with recurrence in the field of radiotherapy alone were assigned into group A, 157 cases with recurrence outside the radiation field alone were allocated into group B (56 cases with lymph node recurrence in group B1, 78 cases with blood metastasis in group B2, and 23 cases with lymph node and blood metastasis simultaneously in group B3), and 36 cases with combined recurrence and metastasis in and out of the field of radiotherapy were assigned into group C. The median survival time of patients in groups A, B1, B2, B3 and C was 13, 24, 13, 11 and 9 months, respectively (all P<0.001). According to the interval from initial diagnosis to recurrence / metastasis, 110 cases were classified in ≤1 year group, 74 cases in >1-2 years group, and 65 cases in >2 years group. The median survival time of patients in the three groups was 11, 14, and 22 months, respectively (all P<0.001). According to the management of recurrence / metastasis, 138 cases received palliative treatment, 15 cases received local treatment, 45 cases received systemic treatment, and 51 cases received combined treatment. The median survival time of patients among four groups was 9, 37, 20 and 32 months, respectively (all P<0.001). The results of multi-factor analysis showed that age, recurrence / metastatic site, retreatment methods, time interval between initial treatment and recurrence /metastasis were the independent prognostic factors affecting the survival (all P<0.05). Conclusions:Distant metastasis is the main failure pattern after radical radiotherapy. Patients with metastasis out of irradiated regions, especially those with only lymph node metastasis, have good prognosis. Active retreatment and time interval between initial diagnosis and recurrence / metastasis are important prognostic factors.

Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

To explore the level of hsa_circ_0001588 in plasma of patients with gastric cancer and to analyze the relationship between the plasma level of hsa_circ_0001588 and clinical characteristic,toll like receptors 4(TLR4)and T lymphocyte subsets,this study enrolled 124 gastric cancer patients who were treated in our hospital from March 2021 to May 2022 as study group.Simultaneously,another 130 patients diagnosed with superficial gastritis by gastroscopy were selected as benign group,and 130 healthy individuals were set as control group.The plasma hsa_circ_0001588 level was measured by quantitative real-time polymerase chain reaction,the plasma level of TLR4 was detected by double antibody sandwich ELISA,and plasma CD3+,CD4+,CD8+,and CD4+/CD8+levels were tested by Wmini5146 flow cytometry.Then the diagnostic efficacy of plasma hsa_circ_0001588,TLR4 and T lymphocytes for gastric cancer was evaluated,and the correlation between the level of hsa_circ_0001588 in plasma and the level of TLR4 and T lymphocytes in gastric cancer patients was verified.Data showed that the levels of hsa_circ_0001588,TLR4 and CD8+in plasma of study group were higher than those of benign group and control group,while the levels of CD3+,CD4+and CD4+/CD8+were lower than those of benign group and control group(P＜0.05).Furthermore,a decrease was observed in plasma hsa_circ_0001588 level in gastric cancer patients after surgery compared to baseline data.Among gastric cancer patients of different clinicopathological characteristics,patients with high clinical stage,high degree of infiltration,poor differentiation and distant metastasis had high plasma hsa_circ_0001588 level(P＜0.05).Diagnostic analysis denoted that the separate test of plasma hsa_circ_0001588,TLR4 and T-lymphocytes all had good diagnostic efficacy for gastric cancer,while combined test showed the highest diagnostic efficacy.Comparison among gastric cancer patients revealed that high hsa_circ_0001588 expression group had lower expression of CD3+,CD4+and CD4+/CD8+,and higher expression of TLR4 and CD8+than those of low hsa_circ_0001588 expression group(P＜0.05),suggesting that plasma hsa_circ_0001588 level was negatively correlated with CD3+,CD4+and CD4+/CD8+expression,but positively correlated with TLR4 and CD8+.In conclusion,the level of hsa_circ_0001588 in plasma is elevated in patients with gastric cancer,and it has a negative correlation with CD3+,CD4+and CD4+/CD8+,but positive correlation with TLR4 and CD8+expression.

Objective:To compare the clinical efficacy and toxicity of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in radical radiotherapy for cervical cancer.Methods:Clinical data of 1002 patients with cervical cancer treated with radical radiotherapy at Zhejiang Cancer Hospital from September 2013 to December 2016 were retrospectively analyzed. All patients were divided into the IMRT group and 3D-CRT group according to the technology of external beam radiation therapy (EBRT). After 1∶1 propensity score matching (PSM), clinical prognosis of patients receiving IMRT or 3D-CRT was compared. Continuous data were expressed as Mean ± SD or median . Categorical data were described by case number (percentage). Quantitative data were compared by t-test. Qualitative data were compared by chi-square test or Fisher's exact test. Survival rates in two groups were calculated by Kaplan-Meier method and log-rank test. Results:The percentage of patients who received pelvic and para-aortic radiotherapy in the IMRT group was significantly higher than that in the 3D-CRT group (14.9% vs. 1.2%, P<0.001). The percentage of patients whose positive lymph nodes dose reached 55 Gy or more in the IMRT group was significantly higher than that in the 3D-CRT group (26.6% vs. 15.5%, P=0.002). In the IMRT group, the 5-year disease-free survival (DFS) rate (74.6% vs. 68.9%, P=0.084) and overall survival (OS) rate (79.4% vs. 74.9%, P=0.270) were slightly higher than those in the 3D-CRT group, but there were no significant differences between two groups. In the IMRT group, the local recurrence (3.0% vs. 6.9%, P=0.020) and distant lymph node metastasis rates (4.2% vs. 9.0%, P=0.013) were significantly lower compared with those in the 3D-CRT group. In terms of acute radiotherapy toxicities, grade 3-4 leukopenia (46.3% vs. 37.9%, P=0.028) and anemia (18.8% vs. 14.0%, P<0.001) occurred significantly more frequently in the IMRT group than in the 3D-CRT group. Conclusions:Both IMRT and 3D-CRT could achieve good therapeutic outcomes in radical radiotherapy of cervical cancer. IMRT can boost the radiation dose of metastatic lymph nodes and has significant advantages in reducing local recurrence and distant lymph node metastasis.

Objective:To evaluate the performance of Autoderm, an artificial intelligence application, in the diagnosis of skin diseases in Chinese patients.Methods:Totally, 920 patients with confirmed skin diseases were prospectively recruited in the Department of Dermatology, the First Affiliated Hospital of Zhengzhou University. Every patient provided 1 clinical image, which was uploaded onto the Autoderm application for the diagnosis of skin diseases. The diagnostic sensitivity, specificity and accuracy of the Autoderm application were estimated, and the kappa values for the diagnostic agreement between the Autoderm application and dermatologists were calculated.Results:Among the 920 patients, 871 (94.7%) could be diagnosed with an Autoderm′s in-distribution skin disease, whereas 49 (5.3%) had out-of-distribution skin diseases. According to the top 1 and 3 diagnoses given by the Autoderm application for the 920 patients separately, its mean diagnostic sensitivities were 41.8% and 65.8%, mean specificities 96.8% and 91.5%, and mean accuracies 92.9% and 89.9%, respectively, and there was moderate overall agreement between the Autoderm application and dermatologists (κ = 0.420, 0.464, respectively). However, for an out-of-distribution skin disease, the Autoderm application could output 5 definitely false diagnoses.Conclusion:Autoderm may be used as as clinical decision support tool for the diagnosis of common skin diseases in most Chinese patients, with moderate diagnostic sensitivity, high specificity, and high accuracy, but misdiagnosis may occur.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

Objective To investigate the correlation between total burden of cerebral small vessel disease (CSVD) and cognitive impairment in patients with acute basal ganglia infarction. Methods Patients with acute basal ganglia infarction for the first time were enrolled, and the general data of the enrolled patients were collected. Patients were assessed by Montreal cognitive assessment (MoCA). Based on MoCA assessment, patients were then divided into cognitive impairment (CI) group and non-cognitive impairment (NCI) group. CSVD total load scores were conducted afterwards in order to analyze the correlation between the total load of different degrees of cerebral small vessel disease and cognitive impairment. Results A total of 178 patients were enrolled in this study: 135 in the CI group and 43 in the NCI group. There were significant differences in age (t=4.11, P=0.04) but not in high-density lipoprotein (t=2.92, P=0.09), and glycosylated hemoglobin C (t=3.02, P=0.08) between the two groups. The infarct volume was larger in the CI group (CI group: 424.72±36.55, NCI group: 227.02±34.62, t=4.022, P=0.046). There were significant differences in a sing1e lentiform nucleus (χ2=19.08, P<0.01), caudal Nucleus(χ2=9.97, P<0.01), infarction at the site of internal capsule(χ2=3.85, P=0.05), the infarct site involved lentiform nucleus, internal capsule and caudate nucleus at(χ2=4.30, P=0.04), and numbers of patients with moderate-to-severe internal carotid artery stenosis (χ2=4.14, P=0.04) as well as numbers of patients with moderate-to-severe intracranial artery stenosis (χ2=4.19, P=0.04). Similarly, there were significant differences in CSVD total burden (t=3.62, P<0.01), deep white matter hyperintensity (t=9.02, P<0.01), and cerebral microbleeds (t=5.54, P=0.02) between CI group and NCI group. The comparisons on MoCA score, visuospatial and execution, attention, language, generalization and abstraction, memory and orientation but not naming were statistically significant between the two groups. The logistic regression equation showed that CSVD total burden (OR=0.316, 95%Cl: 0.185~0.541, P<0.001), age (OR=0.924, 95%Cl: 0.884~0.967, P=0.001) and infarct volume (OR=0.924, 95%Cl: 0.884~0.967, P=0.001), (95%Cl: 1.000~1.003, P=0.047) was significantly associated with cognitive impairment in patients with acute basal ganglia infarction. Conclusion High CSVD total load score, older age and larger infarct volume may be risk factors for cognitive impairment in patients with acute basal ganglia infarction.

Objective:To explore the effect of functional electrical stimulation on cognition and on the expression of the brain-derived neurotrophic factor (BDNF), synaptophysin (SYN) and microtubule-associated protein 2 (MAP2) using a rat model of vascular dementia.Methods:Ninety pathogen-free male Wistar rats were randomly divided into a sham operation group, a placebo stimulation group and an electrical stimulation group. Both the placebo and electrical stimulation groups underwent bilateral occlusion of the common carotid artery to establish a model of vascular dementia. In the sham operation group the arteries were exposed without occlusion. Each group was then sub-divided into 3, 7 and 14 days subgroups with 10 rats in each subgroup. Beginning seven days after the surgery, the rats in the electrical stimulation group were given 30-minutes of stimulation every day while those in the sham operation group and the placebo stimulation group were given false electrical stimulation. After 3, 7 or 14 days the rats′ cognitive functioning was quantified using the Morris water maze test. The rats were then sacrificed and the expression of BDNF mRNA was measured using in situ hybridization. MAP2 and SYN levels were quantified immunohistochemically.Results:After 14 days the average latency in the placebo stimulation group was significantly longer than in the other groups. On the sixth day the average time in the target zone among the placebo stimulation group was significantly shorter than the other two groups′ averages. After only 3 days of simulation, the average expression of BDNF mRNA in the CA1 area of the hippocampus was significantly lower in the placebo stimulation group than among the others. After 7 days of stimulation the placebo group′s average was significantly lower than that of the sham operation group. The average expression of MAP2 had decreased significantly in the placebo stimulation group compared with the other two groups after 7 and 14 days of simulation. After 7 days the average expression of SYN in the placebo stimulation group was significantly lower than in the sham operation group, and after 14 days it was significantly lower than in the other two groups.Conclusions:Functional electrical stimulation may improve learning and memory in rats modelling vascular dementia through increasing BDNF, SYN and MAP2 expression levels.

Objective: To investigate the role of piperine on the transformation of endothelial cells into fibroblasts. Methods: Cultured human umbilical vein endothelial cells (HUVECs, 4-6 passage) were used for the main experiments. The transformation models of endothelial cells into fibroblasts were induced by transforming growth factor β (TGF-β) stimulation. HUVECs were divided into 6 groups: control group, TGF-β group and 4 groups treated with various concentrations of piperine (1, 5, 10, 20 μmol/L). CKK-8 was used to detect cell proliferation. The CD31/α-smooth muscle actin (α-SMA) expression level was detected by fluorescent staining. The vascular endothelial cadherin (VE-cadherin)/vimentin expression was detected by immunofluorescence staining. RT-PCR was used detect the mRNA expressions of transformation markers. Western blot was used to detect the protein expression of snail and twist. Results: TGF-β increased HUVECs proliferation (P<0.05), which could be significantly inhibited by 10 and 20 μmol/L of piperine, but not by 1 and 5 μmol/L of piperine. Immunofluorescence results demonstrated that TGF-β increased HUVECs transformation to fibroblasts as shown by downregulated expression of endothelial markers CD31, VE-cadherin, and upregulated expression of α-SMA and vimentin, again, these effects could be attenuated by 10 and 20 μmol/L piperine. The expression levels of collagen type Ⅰ and type Ⅲ were significantly higher in TGF-β group than in control group (P<0.05), significantly lower in TGF-β+10 μmol/L piperine group and TGF-β+20 μmol/L piperine group than in TGF-β group (P<0.05).In addition, RT-PCR results showed that TGF-β increased mRNA expression of transformation markers (snail1, snail2, twist1, twist2), while 10 and 20 μmol/L of piperine could significantly downregulated the mRNA expressions of these markers. The protein expression levels of snail and twist were significantly higher in TGF-β group than in control group (both P<0.05), which was significantly lower in TGF-β+20 μmol/L piperine group than in TGF-β group (both P<0.05). Conclusions Piperine can inhibit the transformation of endothelial cells into fibroblasts. This effect might be viewed as one of the potential mechanisms of reduced myocardial fibrosis post piperine treatment.