No abstract

Recent phase 1–2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1–5/3–5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1–5 AEs whereas camrelizumab and nivolumab regarding grade 3–5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. 64.1%). Pooled ORR was 28.4 and 17.4% for PD-L1–positive and PD-L1–negative patients, respectively ( P = 0.11). Here, we represent preliminary evidence for the comparative safety and efficacy of existing anti-PD-1 agents with/without chemotherapy in RM-NPC, which indicated that camrelizumab has the least toxicity profile and merits future investigation. Our findings might provide insights into the future design of immunotherapy trials in RM-NPC.

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying renal I/R injury involve inflammation, oxidative stress and apoptosis. Osthole is a coumarin derivative that exhibits potential anti-inflammatory activity. The aim of the present study was to investigate the effect of osthole in renal I/R injury and its underlying mechanism. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy. A total of 70 rats were randomly assigned to seven groups (n=10 per group): Sham; IRI; and osthole (0, 5, 10, 20 and 40 mg/kg) groups. Rats were administered intraperitoneally with osthole 45 min prior to renal ischemia. Serum and renal tissue were harvested 24 h after reperfusion. Renal function and histological changes were assessed. In addition, the mRNA and protein expression of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and interleukin-6 (IL-6) in renal tissue and serum were evaluated using quantitative polymerase chain reaction and ELISA assays, respectively. The protein expression levels of p65, p-p65, janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription 3 (STAT3) and p-STAT3 were measured using western blot analysis. The results indicate that osthole pretreatment was able to significantly attenuate the renal dysfunction in a dose-dependent manner, histological changes and the expression of TNF-α, IL-8, IL-6, p-JAK2, p-STAT3 and p-p65 induced by renal I/R injury. However, neither osthole or I/R injury affected the expression p65, JAK2 and STAT3. Osthole pretreatment is able to reduce renal I/R injury by abrogating inflammation and the mechanism is partially involved in suppressing JAK2/STAT3 activation. Thus, osthole may be a novel practical strategy for the mitigation of renal I/R injury.

China’s diabetes epidemic is getting worse. People with diabetes in China usually have a lower body weight and a different lifestyle profile compared to their counterparts in the United States (US). More and more evidence show that certain lifestyles can possibly be spread from person to person, leading some to propose considering social influence when establishing preventive policies. This study developed an innovative agent-based model of the diabetes epidemic for the Chinese population. Based on the risk factors and related complications of diabetes, the model captured individual health progression, quantitatively described the peer influence of certain lifestyles, and projected population health outcomes over a specific time period. We simulated several hypothetical interventions (i.e., improving diet, controlling smoking, improving physical activity) and assessed their impact on diabetes rates. We validated the model by comparing simulation results with external datasets. Our results showed that improving physical activity could result in the most significant decrease in diabetes prevalence compared to improving diet and controlling smoking. Our model can be used to inform policymakers on how the diabetes epidemic develops and help them compare different diabetes prevention programs in practice.

Background: Studies on the relationship between lifetime body mass index (BMI) trajectory and colorectal premalignant precursor lesions are limited. This study aimed to assess the relationship between prediagnostic adulthood BMI trajectory and the risk of colorectal adenomas using data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.Methods: In total, 39,824 participants in the intervention arm of the prospective PLCO cohort, who have undergone at least one colonoscopy or sigmoidoscopy examination with a confirmed diagnosis of colorectal adenomas, were enrolled and divided into four groups (underweight, normal weight, overweight, and obese) according to BMI during each age period. SAS Proc Traj was used to establish the BMI trajectory model.Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Compared with normal weight, overweight or obesity significantly increased colorectal adenomas risk in each age period after 30 years. Specifically, obesity in the 50s was most closely related to colorectal