Objective To investigate the prevalence of DUOX2 mutations in Chinese patients with congenital hypothyroidism (CH) and to discuss the inheritance pattern of DUOX2 gene.Methods Blood samples were collected from 91 CH children and their genomic DNA was extracted from peripheral blood leukocytes.All exons and exon-intron boundaries of DUOX2 were analyzed by target next-generation sequencing and family trios was established to study the inheritance pattern of DUOX2 gene.Results Fifty-four out of 91 children with CH carried DUOX2 mutation, with a prevalence of 59.34%.Of the 54 CH children, 36 carried DUOX2 biallelic mutations.In all 12 family trios with probands carrying biallelic DUOX2 mutations, the parents carried heterozygous DUOX2 mutations while still showing normal thyroid function, suggesting that CH caused by DUOX2 mutations is inherited in an autosomal recessive manner.Conclusion DUOX2 gene is one of the most frequently mutated genes in Chinese CH patients and its inheritance pattern is an autosomal recessive one.

Objective:To analyze the role of baseline mesorectal fascia (MRF) status and the correlation between MRF changes and prognosis after neoadjuvant therapy in patients with locally advanced rectal cancer.Methods:Totally 321 patients with locally advanced rectal cancer were retrospectively analyzed from January 2014 to December 2016 in Peking University Cancer Hospital. All patients underwent surgery after neoadjuvant radiotherapy and chemotherapy, and were followed up regularly after surgery. The MRF status, extramural vascular invasion (EMVI) status, tumor location, tumor stage and lymph node status were evaluated on baseline MRI. For patients with positive baseline MRF, preoperative MRF status was also evaluated. Chi-square test or independent t test were used to compare the characteristics between MRF positive and negative patients. Kaplan-Meier curve, log-rank test and multivariate Cox regression were used to analyze the correlation between imaging features and prognosis. Results:In all of the 321 subjects, 193 (60.1%) had positive baseline MRF, 54 (28.0%) of the 193 patiens had negative MRF after neoadjuvant therapy, and 139 (72.0%) of them still had positive MRF preoperatively. The postoperative pathological T and N stages were significantly higher in patients with positive baseline MRF than those with negative MRF, and the proportion of patients achieving complete pathological response was significantly lower than those with negative MRF (all P<0.05). The postoperative pathological T and N stages of patients with MRF negative conversion were significantly lower than those without MRF negative conversion. In patients with negative baseline MRF and patients with negative MRF conversion after neoadjuvant therapy, the proportion of positive MRI EMVI was significantly lower (all P<0.05). Univariate survival analysis showed that overall survival and metastasis free survival were poorer in patients with positive MRF at baseline, with a hazard ratio of 3.33 and 1.69, respectively. There was no significant correlation between negative MRF conversion after neoadjuvant therapy and overall survival, metastasis free survival and recurrence free survival. Multivariate Cox analysis showed that baseline MRF and EMVI status were independent factors for overall survival and metastasis free survival, with a risk ratio of 2.15 and 3.35 for overall survival, 1.13 and 2.74 for metastasis free survival, respectively. Conclusions:Baseline MRF status is one of the independent prognostic predictors in locally advanced rectal cancer patients with neoadjuvant therapy. However, the role of the change in MRF status after neoadjuvant therapy is uncertain for predicting prognosis.

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg^-1） groups， and a trimetazidine group （0.002 g·kg^-1）. By intragastric administration of vitamin D₃ and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.