Objective To explore the association between folic acid supplementation during periconcerptional period and congenital heart disease in newborns to provide scientific evidence for making intervening measures.Methods Using stratified random cluster sampling,a total of 30 counties were sampled from Shaanxi Province.A questionnaire survey was conducted among childbearing-aged women pregnant between January 2010 and November 2013.All of the included women had definite pregnancy outcomes and had signed the consent form.Logistic regression was performed to investigate the association between folic acid supplementation during pregnancy and congenital heart disease in newborns.Results In total,28 354 questionnaires were available for analysis.The overall prevalence of congenital heart disease among live-birth neonates in the present study was 7.3‰.The percentage of childbearing-age women who had taken folic acid supplementation during pregnancy was 64.4％,while only 17.2％ of them took folic acid according to the specification.Taking folic acid regularly during pregnancy was associated with a lower risk of congenital heart disease among the newborns (OR 0.502,95％ CI:0.279 0.902).The multiple-factor analysis results also showed that taking folic acid regularly during periconcerptional period could reduce the risk of congenital heart disease (adjusted OR=0.512,P=0.046) when we controlled the family background factors,mother factors and exposure risk factors during pregnancy.However,no association was found between irregularly taking folic acid during periconcerptional period and the risk of congenital heart disease.Conclusion Taking folic acid according to the specification during periconcerptional period (taking folic acid during 3 months before pregnancy to 3 months after pregnancy with a daily dose of 0.4mg for more than 90 days) may prevent congenital heart disease of newborns.

OBJECTIVE: To explore the genetic basis for a Chinese patient featuring cleidocranial dysplasia(CCD). METHODS: Genomic DNA was extracted from peripheral blood samples of the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and suspected variant was verified by Sanger sequencing. RESULTS: WES has identified a missense c.460G>T (p.Val154Phe) (GRCh37/hg19) variant of the RUNX2 gene. The variant was located in the Runt domain, a highly conserved region (PM1); it was not present in either the Genome Aggregation Database or the 1000 Genomes Project (PM2), and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3); the clinical phenotype of the patient was highly consistent with that of cleidocranial dysplasia (PP4). Furthermore, the variant was unreported in medical literature and was absent in both parents (PS2). Based on the American College of Medical Genetics and Genomics guidelines, the c.460 G>T variant of RUNX2 gene was predicted to be pathogenic (PS2+PM1+PM2+PP3+PP4). CONCLUSION The c.460G>T (p.Val154Phe) variant of the RUNX2 gene probably underlay the clinical phenotype in the patient. Above finding has enabled accurate diagnosis and expanded the spectrum of RUNX2 variants.
China ; Cleidocranial Dysplasia/genetics* ; Core Binding Factor Alpha 1 Subunit/genetics* ; Humans ; Mutation ; Whole Exome Sequencing

Ninety six female patients with chronic renal failure were randomly allocated into combination group (n =48) and control group (n =48).In combination group patients received both kidney transplantation and hematopoietic stem cell infusion,in control group patients underwent kidney transplantation only.The results showed that chronic rejection in the combination group was lower than that in the control group [2％(1/48)vs.17％ (8/48),P＜0.05)].The 1-,3-,5-and 10 y-survival rates of kidney in the combination group were 98％ (47/48),94％ (45/48),83％ (34/41) and 9/17,respectively,those in control group were 98％ (47/48),90％ (43/48),76％ (31/41) and 7/17,respectively.Infusion of donor hematopoietic stem cells can augment chimerism in early postoperative period and significantly reduce the rate of graft rejection,which is beneficial for the quality of life of the recipients.

OBJECTIVETo investigate the expression characteristics of human beta-defensin-2 (HBD-2) mRNA and protein in salivary gland benign and malignant tumor tissues, as well as in salivary gland inflammation.

METHODSThe expression of HBD-2 in salivary gland benign tumor, salivary gland cancer, inflammation tissues and normal salivary gland tissues were detected by polymerase chain reaction (PCR), real-time polymerase chain reaction (Real-Time PCR) and immunohistochemical. The differences expression of HBD-2 mRNA and protein were analyzed.

RESULTSRT-PCR results showed that HBD-2 mRNA expression in salivary gland benign tumors, salivary gland cancer, and inflammation tissues was 6.468-, 0.334-, and 10.563-fold higher than that in normal tissues, respectively (P < 0.05). HBD-2 was expressed in the nuclei of these organs and malignant tissues.

CONCLUSIONHBD-2 mRNA and protein expressions are significantly increased in salivary gland benign tumor tissues and inflammation tissues compared with those in normal salivary gland tissues, but are significantly decreased in salivary gland cancer. The protein nuclear transfer in salivary gland cancer tissues is also significantly increased.

Objective: To study the clinicopathological features, diagnostic features and differential diagnoses of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Six cases of SDSC diagnosed at Eye, Ear, Nose and Throat Hospital, Fudan University from 2016 to 2018 were retrieved; the clinical features, histomorphology, immunophenotype, radiology and outcome were analyzed with review of literature. Results: There were five men and one woman with age range of 37 years to 75 years (mean 56 years). One case was in stage T2, and 5 cases were in stage T4. Computer tomography and magnetic resonance imaging showed a mass occupying the sinonasal cavity with bone destruction in all six patients. Microscopically, the tumors had infiltrative margins. Four tumors were composed mostly of basaloid cells, which possessed high nuclear/cytoplasmic ratio,scant cytoplasm,and minimalnuclear pleomorphism; and the cells were arranged in sheets or nests in a desmoplastic stroma. Two tumors were composed of rhabdoid cells, which possessed abundant, eosinophilic cytoplasm and eccentric nuclei, often growing in a nests or sheets pattern. Immunohistochemical staining showed that 6/6 cases had complete loss of INI1, diffusely and strongly positive for CKpan, and were negative for S-100 and EBER ISH; 4/6 cases were focally positive for p63; 1/5 was focally positive for Syn and p16. The Ki-67 index was 30% to 70%. The follow-up period ranged 1-26 months, with one patient died of extensive metastases, one had local recurrence, and two had lymph node metastases; one was alive without disease, and one was lost to follow-up. Conclusions SMARCB1 (INI1)-deficient sinonasal carcinoma is mostly aggressive, with rapid progression and poor prognosis. Histomorphological spectrum predominantly consists of basaloid type and rhabdoid type. The complete loss of nuclear expression of INI1 can help to distinguish this tumor from its many mimickers.

Objective: To investigate the effect of online and offline mindfulness training on improving anxiety and depression and sleep quality of college students,and to provide a reference for mental health promotion among college students. Methods: From October 2020, a total of 1 203 university students from North China University of Technology were screened with the Self rating Anxiety Scale (SAS), Self rating Depression Scale (SDS) and Pittsburg Sleep Quality Index (PSQI) using the whole group radom cluster sampling method. Totally 103 students who met the inclusion criteria were randomly divided into 64 online and 39 offline groups. The degree of improvement in anxiety, depression and sleep quality was assessed after the intervention. Results: The SAS, SDS and PSQI scores of college students after the online and offline the mindfulness training intervention significantly decreased compared with score before the intervention( t =5.57, 5.31, 3.99; 4.88,5.02, 5.88, P <0.01). The difference in the degree of improvement in sleep quality between the two interventions, online and offline, was statistically significant ( t =-2.55， P <0.05). The less the three symptoms of anxiety, depression and sleep were combined in university students, the higher the symptom remission rate of the positive mindfulness training (25% remission rate for all three symptoms together, 40% remission rate for two symptoms together and 100% remission rate for only one symptom). Conclusion Both online and mindfulness training can be used as an effective intervention for sleep, anxiety and depression; offline mindfulness training is more effective than online in improving sleep quality in university students; mindfulness training is more effective in relieving single symptoms.

Background: Peste des petits ruminants (PPR) is a contagious and fatal disease of sheep and goats. PPR virus (PPRV) infection induces endoplasmic reticulum (ER) stress-mediated unfolded protein response (UPR). The activation of UPR signaling pathways and their impact on apoptosis and virus replication remains controversial. Objectives: To investigate the role of PPRV-induced ER stress and the IRE1-XBP1 and IRE1-JNK pathways and their impact on apoptosis and virus replication. Methods: The cell viability and virus replication were assessed by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, immunofluorescence assay, and Western blot. The expression of ER stress biomarker GRP78, IRE1, and its downstream molecules, PPRV-N protein, and apoptosis-related proteins was detected by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. 4-Phenylbutyric acid (4-PBA) and STF-083010 were respectively used to inhibit ER stress and IRE1 signaling pathway. Results: The expression of GRP78, IRE1α, p-IRE1α, XBP1s, JNK, p-JNK, caspase-3, caspase-9, Bax and PPRV-N were significantly up-regulated in PPRV-infected cells, the expression of Bcl-2 was significantly down-regulated. Due to 4-PBA treatment, the expression of GRP78, p-IRE1α, XBP1s, p-JNK, caspase-3, caspase-9, Bax, and PPRV-N were significantly downregulated, the expression of Bcl-2 was significantly up-regulated. Moreover, in PPRV-infected cells, the expression of p-IRE1α, p-JNK, Bax, and PPRV-N was significantly decreased, and the expression of Bcl-2 was increased in the presence of STF-083010. Conclusions PPRV infection induces ER stress and IRE1 activation, resulting in apoptosis and enhancement of virus replication through IRE1-XBP1s and IRE1-JNK pathways.

Objective:To investigate the clinicopathological features, immunophenotype, differential diagnosis and prognosis of sinonasal renal cell-like adenocarcinoma.Methods:Retrospective analysis was performed on the cases of sinonasal carcinoma from August 2014 to December 2018 at Eye, Ear, Nose and Throat Hospital, Fudan University. Renal cell-like adenocarcinoma was screened for clinicopathologic feature analysis, and relevant literatures were reviewed.Results:There were 460 cases of sinonasal carcinoma, among which 70 cases (15.2%) were adenocarcinoma, with five (1.1%) being renal cell-like adenocarcinomas. Four patients were male and one was female, with a mean age of 46.5 years (range 29-52 years). The main clinical manifestations were nasal obstruction and epistasis. A red polypoid mass was found under nasal endoscopy. Imaging showed nasal cavity and ethmoid sinus mass with invasion into surrounding structures and bone destruction. Microscopically, the tumor cells were arranged in nests, alveoli and microcapsules with abundant intervening capillaries, accompanied by hemorrhage. The cytoplasm of the cells was clear with low nuclear grade, and the nucleoli were inconspicuous. In some areas, the tumor invaded bone tissue. Immunohistochemical markers CKpan, CK7, CAⅨ, S-100 and vimentin were positive, with low Ki-67 proliferation index. RCC, CD10, PAX8, p63, SMA, HHF35, Calponin, CD117, TTF-1 and neuroendocrine markers Syn and CHG were all negative. EWSR1 and ETV6 gene rearrangements were not detected by FISH. All five patients underwent surgical resection after initial diagnosis. One patient underwent surgical resection after second recurrence and adjuvant radiotherapy, one patient received postoperative radiotherapy, one patient underwent surgical resection after recurrence, one patient had no recurrence and one patient received radiotherapy after recurrence. All five patients had no distant metastasis and survived without tumor up to December 2019.Conclusions:Primary sinonasal renal cell-like adenocarcinoma is a special subtype of low-grade non intestinal adenocarcinoma, with low incidence and inert biologic behavior. At present, most of the literatures are case reports. Before a diagnosis is made, other primary and metastatic clear cell tumors need to be excluded. Immunohistochemistry is helpful for diagnosis and differential diagnosis. Surgical resection is the mainstay of treatment, and may be supplemented by radiotherapy.

Objective:To investigate the clinicopathologic features, immunophenotype, molecular genetic changes of ETV6-rearranged low-grade sinonasal non-intestinal-type adenocarcinoma (ETV6-RLGSNAC).Methods:Primary sinonasal epithelial malignant tumors were collected from January 2015 to January 2020 in the Department of Pathology, Eye, Ear, Nose and Throat Hospital affiliated to Fudan University. Through morphological observation, immunohistochemical detection and fluorescence in situ hybridization (FISH), ETV6-RLGSNAC was screened out for clinicopathological feature analysis, and relevant literatures were reviewed.Results:There were 550 cases of primary sinonasal epithelial malignant tumors, among which 82 cases were adenocarcinoma. There were 29 cases of low-grade non-intestinal adenocarcinoma, only 3 cases of ETV6-RLGSNAC were screened out. Of the 3 patients, 2 cases were male and 1 case was female, with a mean age of 54 years (range 37-64 years). The main clinical manifestations were nasal stenosis, nasal obstruction and epistaxis. A neoplasm with smooth surfaces was observed under nasal endoscopy. Imaging showed an expansive mass in the sinonasal area. Gross examination showed gray-yellow cut surface with firm texture and a maximum diameter of 2-3 cm. Microscopically, tumors were non-encapsulated and well-circumscribed with expansive growth pattern. The tumor cells were small and mild, cylindrical and cuboidal, and arranged in regular glandular and trabecular patterns. The cytoplasm was eosinophilic and the nuclei were basally located with inconspicuous nucleoli. By immunohistochemistry (IHC), CK7, SOX-10, DOG1 and vimentin were positive and S-100 expressed in small clusters of cells in all cases. GCDFP-15, CD56, CK20, mammaglobin, TTF-1, NR4A3 were all negative. The Ki-67 value-added index of all cases was low (<5%). ETV6 gene rearrangement was confirmed in all the cases by FISH, and two cases had NTRK3 gene rearrangement. All three patients underwent radical resection after diagnosis, and one also had adjuvant radiotherapy. All three patients were available with a follow-up time of 12-25 months, and all were recurrence free.Conclusions:ETV6-RLGSNAC is a rare low-grade and newly named non-intestinal adenocarcinoma. The histomorphology is similar to other low-grade nasal sinonasal adenocarcinomas and some salivary gland tumors. IHC and FISH are useful for the diagnosis and differential diagnosis.