AIM:To investigate the effect of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) on the Notch signaling pathway in a model of oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) damage.METHODS:HUVECs were divided into control group, ox-LDL group, DAPT group and ox-LDL+DAPT group.The morphological changes of the HUVECs with different treatments were observed under light microscope.The viability of the HUVECs was measured by CCK-8 assay.The protein expression levels of Notch1, Notch4 and Jagged1 were determined by Western blot.RESULTS:ox-LDL induced great damage to the HUVECs, evidenced by increased cell death and debris in the culture.However, the cell damage was abolished by adding DAPT into the culture.The viability of the HUVECs was increased by co-treatment with DAPT and ox-LDL.ox-LDL treatment significantly decreased the protein expression levels of Notch1 and Jagged1, and elevated Notch4.However, these changes were totally reversed by DAPT.None of these proteins showed significant change in the HUVECs co-treated with DAPT and ox-LDL as compared with control group.CONCLUSION:ox-LDL is able to induce HUVEC damage in vitro.DAPT attenuates ox-LDL-induced damage in the HUVECs by regulating the Notch signaling pathway.

ObjectiveTo evaluate the local failure and the impact on survival by prospectively comparing involved field radiotherapy (IFRT) and elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer ( LA-NSCLC ).Methods LANSCLC patients were treated with 2 cycles of carboplatin ( AUC =5 - 6,d1 ) combined with paclitaxel ( 175mg/m2 ),followed assessment without distant metastasis,then randomized into IFRT (45 patients) or ENI (54 patients) arm.IFRT included primary tumor,ipsilateral hilar and positive mediastinal lymph nodes;ENI included the primary lesion,ipsilateral hilar,hilateral mediastinal lymph node drainage and bilateral supraclavicular area.The prescription dose was given as high as possible with V20 ≤35％ and spinal cord dose ≤50 Gy,combined weekly paclitaxel 40 mg/m2 concurrent chemotherapy.The Kaplan-Meier method was used to estimate survival data and the log-rank method was used to test distribution of survival time between arms.ResultsThe follow-up rate was 99％.49,29 and 17 patients were followed-up for 1-,2-and 3-year,respectively.More patients from group IFRT received ＞60 Gy than ENI (49％ vs.26％,x2 =5.59,P =0.018 ).The local failure rates were 29％ and 36％,respectively ( x2 =0.46,P =0.497 ).The 1-,2-and 3-year local tumor progression-free survival rates were 76％,69％,65％ and 80％,53％,49％ ( x2 =0.74,P =0.389),respectively; the 1-,3-and 5-year overall survival rates were 80％,41％,33％ and 69％,32％,13％ (x2 =3.97,P =0.046),respectively.There were no significant differences in acute and late toxicities between the arms ( x2 =3.910 - 0.155,P =0.142 - 0.925 ).ConclusionsIFRT improved radiation dose and survival rate and did not increase the failure of elective lymph node region compared with ENI.The toxicities were no differences between IFRT and ENL Further investigation with big size sample is warranted.

ObjectiveTo investigate the possible mechanisms of modified Xiaoyao Powder （逍遥散） in the treatment of hyperprolactinemia （HPRL） with liver constraint and spleen deficiency. MethodsNinety-six female SD rats were randomly divided into a normal group （n=16） and a modeling group （n=80）. In the modeling group， rats were subjected to chronic unpredictable stress combined with intraperitoneal injection of metoclopramide to establish a rat model of HPRL with liver constraint and spleen deficiency. The 80 successfully modeled rats were randomly divided into a model group， a high， medium， and low-dose group of modified Xiaoyao Powder， and a bromocriptine group， with 16 rats in each group. The high， medium， and low-dose groups of modified Xiaoyao Powder were orally administered doses of 60， 30， and 15 g/（kg·d） respectively， the bromocriptine group was orally administered bromocriptine tablets at a dose of 1 mg/（kg·d）， and the normal group and model group were orally administered 10 ml/（kg·d） of normal saline for 14 consecutive days. ELISA was used to detect serum prolactin （PRL） level； immunohistochemistry was used to determine the expression of tumor necrosis factor-alpha （TNF-α） and tyrosine hydroxylase （TH） in the hypothalamus； Western blot was used to detect the protein expression of tumor necrosis factor receptor 1 （TNFR1） in the hypothalamus； Real-time PCR was used to detect the mRNA expression of receptor interacting protein kinase 3 （RIP3） in the hypothalamus； immunofluorescence was used to detect the co-expression of RIP3 and dopamine neurons in the hypothalamus. ResultsCompared with the normal group， the serum PRL levels were increased in the model group， and the expression of hypothalamic TNF-α， TNFR1， RIP3 mRNA， and the co-expression of RIP3 with dopamine neurons were significantly increased， while TH expression was decreased （P＜0.05 or P＜0.01）. Compared with the model group， the expression of hypothalamic TNF-α was decreased in the bromocriptine group and low-dose group of modified Xiaoyao Powder， and the expression of TH was significantly increased in the medium and high-dose groups of modified Xiaoyao Powder and the bromocriptine group. The serum PRL levels， hypothalamic TNFR1 and RIP3 mRNA expression， and the co-expression of RIP3 with dopamine neurons were significantly decreased in all dose groups of modified Xiaoyao Powder and the bromocriptine group （P＜0.05 or P＜0.01）. Compared with the bromocriptine group， the serum PRL level were significantly increased in the high and low-dose groups of modified Xiaoyao Powder， TH expression was significantly increased in the medium-dose group of modified Xiaoyao Powder， hypothalamic RIP3 mRNA expression was decreased in the low-dose group of modified Xiaoyao Powder， and the co-expression of RIP3 with dopamine neurons was significantly increased in the high-dose group of modified Xiaoyao Powder （P＜0.01）. ConclusionModified Xiaoyao Powder can regulate the programmed cell death of hypothalamic dopamine neurons， affect DA expression， and regulate PRL levels， which may be one of its mechanisms in the treatment of HPRL with liver constraint and spleen deficiency.

Objective This study aims to analyze the clinical epidemiology,diagnostic and treatment characteristics of minor patients with maxillofacial fracture and provide a reference for the prevention and treatment.Methods The clinical data of minor patients with maxillofacial fracture in Department of Traumatic and Plastic Surgery,West China Hospital of Stomatology,Sichuan University,from January 1,2015 to December 31,2020 were retrospectively studied and statistically analyzed in terms of age,gender,etiology,anatomic sites and treatment modalities.Results The mean age of the patients was(10.65±5.15)years,and the male-to-female ratio was 1.91∶1.High fall was the primary cause of maxillofacial fractures in minors aged 0-6 years.Traffic accident injuries were the main cause of maxillofacial fractures in minors aged 7-12 and 13-17 years.About 65.13%of the midface and 83.08%non-condylar fractures were mainly treated by surgery,and condylar fractures were treated conservatively in 74.73%and by surgical treatment in 25.27%.Conclusion The etiology of maxillofacial fractures in minors differs at different ages,so prevention strategies should be adjusted according to age.Surgical treatment has become the preferred treatment modality for midface and non-condylar fractures.Conservative treatment is still the main treatment method for condylar fractures,but the proportion of surgical treatment increases.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults. METHODS: From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines. RESULTS: The survey determined 18 patients having genetic variants causing MODY (6 HNF1A , 5 GCK , 3 HNF4A , 2 INS , 1 PDX1 , and 1 PAX4 ). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients. CONCLUSION The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A -, GCK -, and HNF4A -MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.
Humans ; Diabetes Mellitus, Type 2/diagnosis* ; Cross-Sectional Studies ; Mutation ; Prevalence ; Phenotype

Humans ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Multiprotein Complexes/metabolism* ; Neural Stem Cells/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rapamycin-Insensitive Companion of mTOR Protein/metabolism* ; TOR Serine-Threonine Kinases/metabolism*