Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response.

UNLABELLED: Bats harbor severe acute respiratory syndrome (SARS)-like coronaviruses (SL-CoVs) from which the causative agent of the 2002-2003 SARS pandemic is thought to have originated. However, despite the fact that a large number of genetically diverse SL-CoV sequences have been detected in bats, only two strains (named WIV1 and WIV16) have been successfully cultured in vitro These two strains differ from SARS-CoV only in containing an extra open reading frame (ORF) (named ORFX), between ORF6 and ORF7, which has no homology to any known protein sequences. In this study, we constructed a full-length cDNA clone of SL-CoV WIV1 (rWIV1), an ORFX deletion mutant (rWIV1-ΔX), and a green fluorescent protein (GFP)-expressing mutant (rWIV1-GFP-ΔX). Northern blotting and fluorescence microscopy indicate that ORFX was expressed during WIV1 infection. A virus infection assay showed that rWIV1-ΔX replicated as efficiently as rWIV1 in Vero E6, Calu-3, and HeLa-hACE2 cells. Further study showed that ORFX could inhibit interferon production and activate NF-κB. Our results demonstrate for the first time that the unique ORFX in the WIV1 strain is a functional gene involving modulation of the host immune response but is not essential for in vitro viral replication. IMPORTANCE: Bats harbor genetically diverse SARS-like coronaviruses (SL-CoVs), and some of them have the potential for interspecies transmission. A unique open reading frame (ORFX) was identified in the genomes of two recently isolated bat SL-CoV strains (WIV1 and -16). It will therefore be critical to clarify whether and how this protein contributes to virulence during viral infection. Here we revealed that the unique ORFX is a functional gene that is involved in the modulation of the host immune response but is not essential for in vitro viral replication. Our results provide important information for further exploration of the ORFX function in the future. Moreover, the reverse genetics system we constructed will be helpful for study of the pathogenesis of this group of viruses and to develop therapeutics for future control of emerging SARS-like infections.

[A prospective study of adenosine triphosphate-tumor chemosensitivity assay directed chemotherapy in patients with recurrent ovarian cancer].

OBJECTIVE: To investigate the efficacy of adenosine triphosphate (ATP)-tumor chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent epithelial ovarian cancer. METHODS: From August 2010 to June 2012, recurrent epithelial ovarian cancer patients were prospectively enrollmented in Cancer Hospital, Peking Union Medical College,Chinese Academy of Medical Sciences.The entry criteria are as follows: (1) Histologically proven to be epithelial ovarian cancer. (2) Patients of recurrent ovarian cancer with bidimensionally measurable tumor, or ascitic or pleural fluid for testing. (3) Karnofsky performance status > 60. (4) A life expectancy of at least more than 6 months.According to patients desires, they were assigned into two groups: assay-directed therapy group and physician's-choice therapy group, patients' clinical and pathological characteristics, response rate to chemotherapy and progression-free survival (PFS) were compared between two groups. RESULTS: A total of 113 patients with recurrent epithelial ovarian cancer were prospectively enrollmented to assay-directed chemotherapy (n = 56) or physician's-choice chemotherapy (n = 57).There was no difference in median age,types of recurrence, surgical-pathological stage, pathological type, tumor grade, times of recurrence, residual disease at secondary cytoreductive surgery between assay-directed group and physician's-choice group. The overall response rate (ORR) and median PFS in the ATP-TCA group was 66% (37/56) and 7 months, while the ORR in the control group was 46% (26/57, P = 0.037), the median PFS was 4 months (P = 0.040). For platinum-resistant patients, the ORR between ATP-TCA directed chemotherapy 59% (16/27) and control group 25% (7/28) were significantly different (P = 0.010), and the median PFS between two groups were also significantly different (5 months and 2 months, respectively, P = 0.003). CONCLUSION: ATP-TCA directed chemotherapy could improve ORR and PFS in patients with recurrent epithelial ovarian cancer, especially in platinum-resistant patients.

Functioning gonadotroph adenoma with hyperestrogenemia and ovarian hyperstimulation in a reproductive-aged woman: A case report and review of literature.

BACKGROUND: Functioning gonadotroph adenomas are extremely rare pituitary tumors that secrete gonadotropins and exhibit distinct clinical manifestations. Here, we report a case of functioning gonadotroph adenoma in a reproductive-aged woman and discuss its diagnosis and management. CASE SUMMARY: A 21-year-old female patient with abdominal pain, irregular menstruation, hyperestrogenemia, and an ovarian mass was included. Brain magnetic resonance imaging (MRI) revealed a pituitary macroadenoma, and transsphenoidal surgery relieved her clinical symptoms. Before transsphenoidal surgery, plasma CA125, estradiol levels were elevated, while prolactin, luteinizing hormone, follicle-stimulating hormone, PROG, cortisol, FT4, thyroid-stimulating hormone, parathyroid hormone, and GH levels were maintained at normal levels. After transsphenoidal surgery, the patient was diagnosed with a functioning gonadotroph adenoma. During follow-up, pelvic ultrasound confirmed normal-sized ovaries in the patient, the menstrual cycle returned to regular, and her hormones were maintained within a normal range. There was no evidence of tumor recurrence after two years of follow-up. CONCLUSION: Early diagnosis of functioning gonadotroph adenomas should be considered in patients with hyperestrogenism, irregular menstruation, large or recurrent ovarian cysts, and visual field defects. Pituitary MRI should be performed, and transsphenoidal surgery is recommended for the management of this disease.

Time Intervals between Double Primary Breast and Ovarian Cancers and Survival Outcomes of Patients with Both Cancers: A SEER Database Analysis.

Background: The time interval rules and survival outcomes of individuals with synchronous and metachronous breast cancer (BC) and ovarian cancer (OC) were examined in this retrospective population-based investigation. Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to create a cohort of people diagnosed with BC and OC between 1973 and 2015. Patients were separated into three groups: those with main BC followed by primary OC (group 1), those with synchronous primary breast and ovarian cancer (group 2), and those with OC prior to BC (group 3). The Kaplan-Meier technique was used to assess overall survival (OS) and cancer-specific survival (CSS). Results: A total of 4,975 patients were identified: 2,929 patients in group 1, 680 patients in group 2, and 1,366 patients in group 3. The average duration between these tumors was 60 months (range 0-499). Approximately 50% of second primary cancer cases occurred during the first 60 months of the first primary cancer diagnosis, and more than 70% occurred within the first 120 months. The median survival time for 4,975 individuals was 140 months. Group 2 had the smallest median OS (35 months), whereas group 3 had the longest (45 months) (239 months). Conclusions: The majority of second primary cancer cases occurred during the first 120 months following the diagnosis of the first original malignancy. Individuals who had primary OC prior to BC had better prognoses, whereas patients who had synchronous BC and OC had worse prognoses.

Prognostic significance of lymph node metastasis and lymphadenectomy in early-stage ovarian carcinosarcoma.

BACKGROUND: The role that lymph node dissection (LND) plays in the management of ovarian carcinosarcoma (OCS) is unclear due to its rarity. This study investigated lymph node metastasis (LNM) prevalence in women with early OCS and effects of LND and LNM on survival. METHODS: Data of women diagnosed with OCS, whose primary tumor was confined to ovaries (American Joint Committee on Cancer [AJCC] T1) or pelvic cavity (AJCC T2), between 1988 and 2010 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were classified into lymphadenectomy (LND [+]) and no lymphadenectomy (LND [-]) groups. RESULTS: A total of 363 women were included. The prevalence of LNM was 9.6% in AJCC T1 and 16.3% in AJCC T2. Multivariate analysis showed that LND and AJCC T categories were independent prognostic variables, irrespective of cancer-specific survival (CSS) or overall survival (OS). Subgroup analysis by AJCC T categories revealed that LND (+) group in AJCC T2 had a better survival outcome compared to LND (-) group (CSS, HR [95% CI] = 0.61 [0.43-0.87]; OS, HR [95% CI] = 0.59 [0.42-0.83]). There was no survival difference between groups in AJCC T1 (CSS, HR [95% CI] = 0.96 [0.56-1.65]; OS, HR [95% CI] = 0.88 [0.56-1.38]). Multivariate analysis was further carried out in LND (+) group and demonstrated that LNM and AJCC T2 had poor CSS and OS. Subgroup analysis by AJCC T categories showed that worse survival was observed in LNM (+) group compared to LNM (-) group in AJCC T2 (CSS, HR [95% CI] = 3.62 [1.50-8.73]; OS, HR [95% CI] = 3.71 [1.59-8.68]) but not in AJCC T1 (CSS, HR [95% CI] = 1.78 [0.50-6.37]; OS, HR [95% CI] = 1.97 [0.61-6.39]). CONCLUSION: Regional lymphadenectomy should be performed in patients with AJCC T2 OCS. LND and LNM were not significantly associated with prognosis in AJCC T1 while LNM had a trend toward worse survival.

[Studies on the chemical constituents in herbs of ethanolic extract from herbs of Dicliptera chinensis].

OBJECTIVE: To study the chemical constituents of ethanolic extract from herbs of Dicliptera chinensis. METHOD: The compounds were separated by silica gel column chromatography, preparation TLC and reverse phase HPLC, their structures were identified by the spectroscopic methods of UV, NMR and MS. RESULT: Seven compounds were isolated from ethyl acetate extract. Their structure were identified as octasulphur (1), secoisolariciresinol dimethyl ether diacetate (2), 5-methoxy-4, 4'-di-O-methyl secolariciresinol (3), chinensinaphthol methyl ester (4), loliolide (5), beta-sitosterol 3-O-beta-D-glucopyranoside (6) and stigmasterol 3-O-beta-D-glucopyranoside (7). CONCLUSION: All the compounds except 6 were obtained from the plants of Dicliptera for the first time.

[Studies of Dynamic Adsorption Behavior of VOCs on Biochar Modified by Ultraviolet Irradiation].

Coconut shell based biochar was modified by ultraviolet irradiation with UV light at a wavelength of 365 nm in order to enhance the adsorption capacity for volatile organic compounds (VOCs). The breakthrough curves of biochars for adsorbing two typical VOCs (benzene and toluene) were examined. The results showed that the adsorption capacity of modified biochar was greatly increased. The saturation adsorption capacity of modified biochar for benzene and toluene was increased to 122.80 mg·g-1 and 236.36 mg·g-1, comparing to that of the pristine biochar (7.27 mg·g-1 and 7.98 mg·g-1, respectively). The breakthrough time of modified biochar for benzene and toluene (390 min and 620 min) was also drastically prolonged as compared to the raw biochar (1 min and 2 min). The characterization analysis of biochars suggested that the carboxylic groups and external surface area were largely enriched, which might be the main factor responsible for the enhanced adsorption of the two VOCs on the modified biochar. The processes of adsorbing benzene and toluene at different concentrations on modified biochar were fitted by Yoon-Nelson, Thomas and BDST models. The result demonstrated that these three models could provide good fitting and the correlation coefficients were all above 0.992. The TG-DTG result proved that ultraviolet irradiation had little effect on the thermal stability of biochar. The modified biochar after adsorption saturation could be reused after thermal regeneration and the regenerated char also had high adsorption capacity after five times of repeated utilization.