The relative importance of fallopian tube (FT) compared with ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs. A collection of transcriptome data of 80 FTs, 89 OSEs, and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and OSE-like tumors. A molecular signature was developed for identifying tissue origin of SOC and then was used to reevaluate the prognostic genes and therapeutic biomarkers of SOC of different tissue origins. IHC staining of tissue array and functional experiments on a panel of ovarian cancer cell lines were used to further validate the key findings. The expression patterns of tissue-specific genes, prognostic genes, and molecular markers all support a dualistic tissue origin of SOC, from either FT or OSE. A molecular signature was established to identify the tissue identity of SOCs. Surprisingly, the signature showed a strong association with overall survival (OSE-like vs. FT-like, HR = 4.16; 95% CI, 2.67-6.48; < 10). The pharmacogenomic approach revealed AXL to be a therapeutic target of the aggressive OSE-derived SOC. SOC has two subtypes originated from either FT or OSE, which show different clinical and pathologic features. .
ObjectiveTo determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19). DesignLiving systematic review and meta-analysis. Data sOurcesMedline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 26 June 2020, along with preprint servers, social media, and reference lists. stuDy selectiOnCohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19. Data extractiOnAt least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly. results 77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I 2 =74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I 2 =0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I 2 =0%) and invasive ventilation (1.88, 1.36 to 2.60; I 2 =0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I 2 =9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I 2 =0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I 2 =0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I 2 =12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I 2 =0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I 2 =0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I 2 =55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I 2 =1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I 2 =not estimable; 1 st...
Background: Multiple sclerosis (MS) is a leading cause of disability among young adults and effects considerable social and economic burdens. Data of MS incidence in China at the national level is lacking. We conducted the first nationwide hospital-based study to estimate the incidence and hospitalization burden of MS in China. Methods: This study is based on an administrative database of the National Hospital Quality Monitoring System, which covers all 1665 tertiary hospitals in mainland China. The "Medical Record Homepage" of all patients, including 346 variables including demographic characteristics, diagnoses, procedures, and expenses etc., were uniformly collected across each tertiary hospital via standard protocol. MS was defined by the 2010 International Panel criteria for MS and was identified by ICD-10 code (G35 • 0). Findings: We identified 27,336 hospital admissions for 15,060 MS patients from 2016 to 2018; amongst these patients, 9,879 were newly diagnosed. The age-and sex-adjusted incidence per 10 0,0 0 0 personyears is 0 • 235 (95% confidence interval [CI] 0 • 230-0 • 240), with 0 • 055 (0 • 050-0 • 060) in children and 0 • 288 (0 • 282-0 • 294) in adults, respectively. The female to male ratio is 2 • 02; the peak disease onset is age of 40-49 years. Residents in high-latitude and high-altitude areas are more likely to develop MS (F = 8 • 99; p < 0 • 001). Prevalent comorbidities include hypertension (18 • 8%), diabetes (7 • 2%), stroke (14 • 7%), depression or anxiety (3 • 7%), and autoimmune disease (2 • 3%). Through 2016-2018, 104 adults and 2 children died, with a hospital mortality rate of 9 • 9 per 1,0 0 0 person-years. Interpretation: For the first time, we obtain the national incidence of MS as 0.055 in children and 0.288 in adults per 10 0,0 0 0 in China. The geographical distribution of MS incidence presented a north-south latitude gradient and a west-east altitude gradient.
Osteosarcoma (OS) is an aggressive bone tumor, and proto-oncogene c-Fos is involved in this lethal disease. However, the role and molecular mechanism of c-Fos in the development and progression of OS remain enigmatic. As one of the Wnt family members, Wnt2 is closely associated with the development of several malignant tumors. In the present study, the expression of c-Fos, Wnt2, and its receptor Fzd9 in human OS tissues, MG63 OS cell line, and human osteoblast hFOB 1.19 cell line was detected by Western blot analysis, immunohistochemical staining, or reverse transcription-polymerase chain reaction. The role of c-Fos in the OS was clarified by treating MG63 cells with small interfering RNA to knockdown c-Fos. Then, cell migration and invasion were assayed by transwell assays and wound healing assay; cell proliferation was assayed by MTS method and 5-ethynyl-2'-deoxyuridine DNA proliferation in vitro detection; cell apoptosis was assayed by flow cytometric method. Co-immunoprecipitation kit was used to confirm the relationship between c-Fos and Wnt2/Fzd9. We found that the expression of c-Fos, Wnt2, and Fzd9 protein was distinctly higher in human OS tissues than that in the adjacent non-cancerous tissues, and their expression in the MG63 OS cell line was markedly increased compared with that in the human osteoblast hFOB 1.19 cell line. Knockdown of c-Fos inhibited the proliferation, migration, and invasion of MG63 cells, and promoted the apoptosis of MG63 cells. Moreover, knockdown of c-Fos inhibited the expression of Wnt2 and Fzd9 mRNA and protein. Our data enforced the evidence that knockdown of c-Fos inhibited cell proliferation, migration, and invasion, and promoted the apoptosis of OS cells accompanied by altered expression of Wnt2 and Fzd9. These findings offer new clues for OS development and progression, and c-Fos may be a potential therapeutic target for OS.
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