Our objective was to determine metabolic syndrome (MS) prevalence in Chinese patients with systemic lupus erythematosus (SLE) and to investigate the conditions that contribute to its development. 116 patients with SLE classified according to the American College of Rheumatology (ACR) classification criteria, and 115 controls were enrolled. MS was defined by the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity (IDF/NHLBI/AHA/WHF/IAS/IASO). SLE features and treatment of SLE were assessed. Fasting insulin and cortisol levels of 30 newly diagnosed, untreated patients and 33 age and sex-matched controls were detected. MS prevalence was 34.2% in patients with SLE and 14.8% in controls (p=0.002). Lupus patients with MS had less frequency of hydroxychloroquine (HCQ) intake (16.0% vs 45.8%; p=0.012). Untreated patients with SLE had higher levels of fasting insulin (10.92 ± 13.53 vs 5.48 ± 5.43 uU/mL, p<0.001) and plasma cortisol at 16:00 (257.22 ± 177.98 vs 139.84 ± 63.46 nmol/L, p=0.001), but lower plasma cortisol at 08:00 (195.51 ± 149.84 vs 278.95 ± 136.27 nmol/L, p=0.024). Comparisons regarding steroid therapy, levels of insulin and cortisol were not statistically significant between patients with MS and without MS. The Chinese patients with SLE presented a higher MS prevalence and fasting insulin than controls. MS was not associated with the steroid therapy and plasma cortisol. HCQ use proved to be protective against MS. The circadian rhythm of cortisol may differ in patients with SLE.

The telomeric protein TRF2, involving in telomeric and extratelomeric DNA damage response, has been previously reported to facilitate multidrug resistance (MDR) in gastric cancer cells by interfering ATM-dependent DNA damage response induced by anticancer drugs. Rap1 is the TRF2-interacting protein in the shelterin complex. Complex formation between Rap1 and TRF2 is essential for their function in telomere and end protection. Here we focus on the effects of Rap1 on TRF2 function in DNA damage response induced by anticancer drugs. Both Rap1 and TRF2 expression were upregulated in SGC7901 and its MDR variant SGC7901/VCR after etoposide treatment, which was more marked in SGC7901/VCR than in SGC7901. Rap1 silencing by siRNA in SGC7901/VCR partially reversed the etoposide resistance. And Rap1 silencing partially reversed the TRF2-mediated resistance to etoposide in SGC7901. Rap1 silencing did not affect the TRF2 upregulation induced by etoposide, but eliminated the inhibition effect of TRF2 on ATM expression and ATM phosphorylation at serine 1981 (ATM pS1981). Furthermore, phosphorylation of ATM targets, including γH2AX and serine 15 (S15) on p53, were increased in Rap1 silencing cells in response to etoposide. Thus, we confirm that Rap1, interacting with TRF2 in the shelterin complex, also has an important role in TRF2-mediated DNA damage response in gastric cancer cells treated by etoposide.

Introduction: Current treatment of primary CNS lymphoma (PCNSL) is a high-dose methotrexate (HD-MTX)-based polychemotherapy. The addition of cytarabine to HD-MTX-based chemotherapy improves clinical outcomes, however the combination therapy increases toxicity. Sequential chemotherapy may decrease toxicity without altering efficacy. This study aimed to analyze efficacy and safety of sequential chemotherapy and cranial radiation for newly diagnosed PCNSL patients. Methods: This was a single center, retrospective cohort study of consecutive newly diagnosed immunocompetent PCNSL patients treated with HD-MTX (5 cycles of 3 g/m 2 every 2 weeks) followed by consolidation WBRT (total 46 Gy) and cytarabine (2 cycles of 3 g/m 2 /d for 2 days every 3 weeks) from January 2013 to December 2020. Initial WBRT before HD-MTX was allowed in patients with Karnofsky performance status less than 70%. Primary outcome was progression-free survival (PFS). Key secondary outcomes were response rate, treatment-related toxicity, and overall survival (OS).Results: Of 41 patients, 25 patients had complete response (CR) and 10 patients had partial response, which inferred to an overall response rate (ORR) of 85.4% and a CR rate of 60.9%. More than 90% of patients were able to tolerate and complete HD-MTX. Twenty-one patients (51.2%) received initial WBRT before chemotherapy. The incidence of ≥ grade 3 hematologic and non-hematologic toxicities were 4.8% and 17.1%, respectively. Treatment-related mortality rate was 2.4%. There was no difference in toxicity between patients with age < 60 and ≥60 years. At the median follow-up duration of 39.8 months, median PFS was 35.2 months (95%CI 12.4 -69.3) and median OS was 46.5 months (95%CI 21.8 -NR). Conclusion:High-dose methotrexate followed by consolidation whole-brain radiotherapy and cytarabine has acceptable efficacy, great tolerability, and low toxicity in newly diagnosed PCNSL patients.