The role of host immune responses in the pathogenesis of borrelial dissemination in early Lyme borreliosis (LB) in the form of multiple erythema migrans (MEM) or LB-associated symptoms is incompletely understood.

In this study, fifteen cytokine or chemokine levels, representative of innate, Th1, and Th17 immune responses, were assessed using a bead-based Luminex multiplex assay in acute sera from 76 adult patients with skin culture-positive Borrelia afzelii solitary erythema migrans (SEM) and 58 patients with MEM at a single-center university hospital. Differences between the groups were tested by modeling each cytokine or chemokine concentration by means of left-censored regression using the classic Tobit model.

Mean serum cytokine or chemokine levels were low. SGC0946 When taking into account the proportion of patients with cytokine or chemokine concentrations below the lowest detectable limit, only levels of CXCL10 (p = .03) and CCL19 (p = .02), representatives of the Th1 immune response, differed between pa-associated symptoms. Localized immune responses in the skin or other pathogenetic mechanisms may be more important in this regard.6,8-Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8-diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8-diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8-Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose- and time-dependent manner. A 40 μM of 6,8-diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8-diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8-diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen-activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8-diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N-acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8-diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8-diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8-diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS.

Interpregnancy interval (IPI) is defined as the period between a live birth and the conception of a subsequent fetus. Both short (IPI < 6 months) and long IPI (IPI > 60 months) havebeen shown to increase the risk for adverse perinatal outcomes, some of which, are known risk factors for obstructive sleep apnea syndrome (OSAS) in the offspring.

To study the association between IPI and risk for offspring OSAS, during a follow-up period of up to 18 years.

Population-based cohort.

In this population-based cohort analysis, all singleton live births, born to a mother with at least one previous birth occurring between 1991 and 2014, were included. Congenital malformations were excluded.

Hospitalizations of the offspring due to OSAS diagnosis up to 18 years of age, were evaluated according to IPI length. Intermediate IPI (6-60 months) was considered as the reference. A Kaplan-Meier survival curve and a Cox hazards regression model were used to compare the incidence of OSAS between the groups, and to adjust for confounding variables.

The study population included 144,397 deliveries, of which 13.1% (n = 18,947) were followed by short IPI, 7.9% (n = 11,438) and 79.0% (n = 114,012) were followed by long and intermediate IPI, respectively. OSAS hospitalization rates were significantly higher among the long IPI group compared to intermediate and short IPIs (0.9%; 0.7% and 0.6%, respectively, p = .001). The association between long IPI and offspring pediatric OSAS remained significant after controlling for preterm delivery, maternal diabetes, and smoking, and mode of delivery, (adjusted HR = 1.45; 95% CI, 1.17-1.80).

Children born following long IPI are at increased risk for pediatric OSAS.

Children born following long IPI are at increased risk for pediatric OSAS.

Despite numerous chimeric antigen receptor T-cell (CAR-T) trials conducted in China, no CAR-T has been registered in the country. Furthermore, China law and regulations restrict the export of patient material for CAR-T manufacture abroad. Relma-cel (JWCAR029), an anti-CD19 product produced with a commercial-ready process in China, was evaluated in the first prospective, single-arm, multicenter, pivotal study of CAR-T therapy conducted under Chinese IND to support an NMPA-accepted BLA submission in relapsed/refractory (r/r) LBCL (NCT04089215).

Patients were randomized to receive either 100×10

(low dose, n=27) or 150×10

(high dose, n=32) CAR+ T-cells as a single infusion following lymphodepleting chemotherapy (fludarabine 25mg/m

and cyclophosphamide 250mg/m

daily×3), and then, monitored for efficacy and safety outcomes and pharmacokinetics. The primary endpoint was ORR at 3months, as assessed by the investigators. Secondary endpoints included DOR, PFS, OS, and adverse event frequency/severity and cell expansion kinetics.

As of the data cutoff on 17 June 2020, 68 patients were enrolled, and 59 were treated. Among the 58 efficacy-evaluable patients, the primary endpoint of 3month ORR was 60.3% (95% CI, 46.6-73.0), excluding the null hypothesis rate of 20%. Any grade and severe grade CRS occurred in 47.5% and 5.1%, respectively, and any grade and severe grade neurotoxicity events occurred in 20.3% and 5.1%.

Relma-cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR-T-associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China.

Relma-cel met the primary endpoint analysis and demonstrated a high rate of durable responses and low rate of CAR-T-associated toxicities in patients with r/r LBCL in a multicenter trial supporting regulatory submission in China.