Association Between RET Fusions and Efficacy of Pemetrexed-based Chemotherapy for Patients With Advanced NSCLC in China: A Multicenter Retrospective Study

BackgroundRearranged during transfection (RET) proto-oncogene gene fusions are rare in non–small-cell lung cancer (NSCLC). We compared the efficacy of pemetrexed-based chemotherapy with other chemotherapy regimens in patients with NSCLC with different RET fusion subtypes.Patients and MethodsA retrospective, multicenter study of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas was conducted. RET rearrangements were detected using next generation sequencing. We analyzed the clinical characteristics of patients with RET-rearranged NSCLC and the efficacy of chemotherapy regimens. We also evaluated the efficacy between groups of patients with and without KIF5B-RET–rearranged lung cancer.ResultsWe evaluated 62 patients with NSCLC and RET rearrangements, including 41 with KIF5B-RET, 15 with CCDC6-RET, and 6 with other rare fusion subtypes. Of these 62 patients, 50 had stage IIIB/IV. We also evaluated 40 patients with first-line chemotherapy information available. The median progression-free survival was significantly different between those receiving pemetrexed-based chemotherapy and those receiving other chemotherapy regimens (9.2 vs. 5.2 months; P = .007). The median progression-free survival for patients with KIF5B-RET fusion and non–KIF5B-RET fusion was not significantly different statistically (7.8 vs. 11.2 months; P = .847). For second-line chemotherapy, a statistically significant difference was found between the chemotherapy regimens (4.9 vs. 2.8 months; P = .049). Survival follow-up data were available for 38 patients with advanced NSCLC. The median overall survival was 26.4 months. The overall survival of the patients with RET-rearranged NSCLC who had received pemetrexed-based chemotherapy versus no pemetrexed-based chemotherapy was 35.2 versus 22.6 months (P = .052). No difference in survival was observed between the patients with KIF5B-RET and non–KIF5B-RET rearrangements.ConclusionsPemetrexed-based treatment should be considered first when selecting the chemotherapy regimen for patients with NSCLC and RET rearrangements.     

Preventive effects of interleukin-6 in lipopolysaccharide/d-galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages

Lipopolysaccharide/d-Galactosamine (LPS/d-Gal)-induced acute liver injury is characterized by significant inflammatory responses including TNF-α and interleukin-6 (IL-6) and is a widely applied experimental model for inflammation research. TNF-α is critical in the progression of LPS/d-Gal-induced liver injury. However, the role of IL-6 in this model is still unknown. In the present study, we aim to elucidate the involvement of IL-6 in the pathogenesis of acute liver injury induced by LPS/d-Gal in mice and its underlying mechanism. To induce acute liver injury, LPS (50 μg/kg body weight) and d-Gal (400 mg/kg body weight) were injected intraperitoneally in the C57BL/6 mice. The vehicle (saline) or a single dose of recombinant IL-6 (200 μg/kg body weight) was administered 2 h prior to LPS/d-Gal injection. Mice were sacrificed 2 h and 6 h after LPS/d-Gal injection. The results indicated that IL-6 treatment could protect mice from LPS/d-Gal-induced tissue damage, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, in vitro study showed that IL-6 treatment could significantly suppress LPS-triggered expression of proinflammatory cytokines and chemokines, TNF-α, RANTES and MCP-1 in macrophages while promoting the expression of M2 markers, such as Arg-1 and Mrc-1 in macrophages. Taken together, these findings revealed a novel and unexpected role of IL-6 in ameliorating LPS/d-Gal-induced acute liver injury via regulating inflammatory responses in hepatic macrophages.     

青蒿素对大鼠心梗后交感神经重构的影响及其机制研究

目的研究青蒿素对大鼠心梗后交感神经重构的作用并探索其分子机制。方法 SD雄性大鼠70只,随机分成3组,假手术组10只,心梗组30只,心梗治疗组30只。开胸结扎冠状动脉左前降支制造心梗动物模型,术后24 h开始灌胃大鼠,心梗治疗组给予青蒿素75 mg/(kg·d),每天分3次灌胃,心梗组给予等剂量的0.5%羧甲基纤维素钠。假手术组开胸仅冠状动脉下穿线但不结扎,同时给予等剂量的0.5%羧甲基纤维素钠。治疗4周后,将动物处死并按需要取材。Masson染色法测量左室梗死面积,免疫组织化学定量分析梗死周边区生长相关蛋白(growth associated protein 43,GAP43)与酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性交感神经纤维的分布和密度及巨噬细胞数目,蛋白免疫印迹法检测梗死周边区IKBα、GAP43、TH、NGF等的表达。RT-PCR检测心肌组织炎症因子TNF-α和IL-1β的mRNA表达水平。结果心梗组与心梗治疗组心梗面积没有显著差异。心梗组GAP43和TH阳性交感神经纤维密度高于假手术组(P<0.05),心梗治疗组GAP43和TH阳性交感神经纤维密度低于心梗组(P<0.05)。心梗组TNF-α和IL-1β的mRNA高于假手术组(P<0.05),心梗治疗组炎症因子TNF-α和IL-1β的mRNA低于心梗组(P<0.05)。心梗组IKBα蛋白高于假手术组(P<0.05),心梗治疗组IKBα蛋白表达低于心梗组(P<0.05)。心梗组NGF、GAP43及TH蛋白的表达高于假手术组(P<0.05),心梗治疗组NGF、GAP43及TH蛋白的表达水平低于心梗组(P<0.05)。梗死组巨噬细胞数目比假手术组高,而心梗治疗组巨噬细胞数目低于心梗组(P<0.05)。结论青蒿素可以抑制心梗后交感神经重构,其机制可能是通过抑制心梗后炎症反应。     

Recurrence hazard rate in patients with hepatocellular carcinoma and bile duct tumor thrombus: a multicenter observational study

BackgroundPatients with hepatocellular carcinoma (HCC) bile duct tumor thrombus (BDTT) have a high rate of postoperative recurrence. We aimed to describe the patterns and kinetics of recurrence in BDTT patients and provide management options accordingly.MethodsThis retrospective study included 311 HCC patients with BDTT who underwent surgery from 2009 to 2017 at five centers in China. The hazard rate of recurrence was calculated using the hazard function.ResultsThe hazard rate of intrahepatic recurrence was higher than that of extrahepatic recurrence (0.0588 vs. 0.0301), and both showed a decreasing trend, and the intrahepatic recurrence and extrahepatic recurrence risk decreased to a lower level after 40 and 20 months, respectively. Patients who underwent anatomic resection had a consistently lower hazard rate of recurrence than patients who underwent nonanatomic resection, whereas patients who received postoperative adjuvant transarterial chemoembolization (TACE) mainly had a lower hazard rate of recurrence in the first year than patients who did not.ConclusionThe follow-up of BDTT patients should be at least 40 months because of its high rate of recurrence, in parallel with the need for vigilance for extrahepatic recurrence within 20 months. Anatomic hepatectomy and adjuvant TACE are recommended to improve BDTT patient outcomes.     

Association of robotic approach with patient-reported outcomes after pancreatectomy: a prospective cohort study

BackgroundRobotic-assisted pancreatectomy continues to proliferate despite limited evidence supporting its benefits from the patient's perspective. We compared patient-reported outcomes (PROs) between patients undergoing robotic and open pancreatectomies.MethodsPROs, measured with the FACT-Hep, FACT-G, and HCS, were assessed in the immediate postoperative (i.e., preoperative to discharge) and recovery (i.e., discharge to three months postoperative) periods. Linear mixed models estimated the association of operative approach on PROs. Minimally important differences (MIDs) were also considered.ResultsAmong 139 patients, 105 (75.5%) underwent robotic pancreatectomies. Compared to those who underwent open operations, those who underwent robotic operations experienced worse FACT-Hep scores that were both statistically and clinically significant (mean difference [MD] 8.6 points, 95% CI 1.0–16.3). Declines in FACT-G (MD 4.3, 95% CI ?1.0 to 9.6) and HCS (MD 4.3, 95% CI 0.8–7.9) scores appeared to contribute equally in both operative approaches to the decline in total FACT-Hep score. Patients who underwent robotic versus open operations both statistically and clinically significantly improved due to improvements in HCS (MD 6.1, 95% CI 2.3–9.9) but not in FACT-G (MD 1.2, 95% CI ? 5.1-7.4).ConclusionThe robotic approach to pancreas surgery might offer, from the patient's perspective, greater improvement in symptoms over the open approach by three months postoperatively.     

Factors influencing extrauterine growth retardation in singleton-non-small for gestational age infants in China: A prospective multicenter study

BackgroundThe incidence of extrauterine growth retardation (EUGR) varies considerably in different countries due to the distinct definitions and inclusion criteria of individual studies. Most studies included small for gestational age (SGA) very preterm infants (VPIs), resulting in a higher incidence of EUGR. Experts have suggested the accurate definition of “EUGR” in SGA infants is not “true EUGR”. The postnatal growth curve of multiple premature births also differs from that of singletons. As far as we know, there is no study about relationship between singleton-non-SGA preterm infants and EUGR.ObjectivesTo analyze the factors influencing EUGR among VPIs who were singleton-non-SGA in China.MethodsA prospective-multicenter study was conducted in 28 hospitals distributed through China from September 2019 to December 2020. The clinical data on singleton-non-SGA among VPIs were divided into EUGR group (n = 692) and non-EUGR group (n = 912).ResultsCompared to non-EUGR group, the mean gestational age (GA), mean birth weight (BW) and percentage of BW in Fenton curve in EUGR group were lower (P < 0.001 for all). The incidence of EUGR among distinct GA groups (classifications of GA < 28weeks, 28–28⁺⁶ weeks, 29–29⁺⁶ weeks, 30–30⁺⁶ weeks and 31–31⁺⁶ weeks) and distinct BW groups (classifications of BW<1000 g, 1000–1249 g, 1250–1499 g, 1500–1999g and 2000–2500 g) were statistically significant (P = 0.004 and P <.001). Logistic regression analysis indicated that later addition of human milk fortifier (HMF), later attainment of HMF sufficient fortification, later return to BW, more accumulative days of fasting, longer duration of parenteral nutrition, total duration of oxygen support and moderate/severe bronchopulmonary dysplasia (BPD) were risk factors for the development of EUGR in singleton-non-SGA VPIs (P < 0.001, P = 0.002, P < 0.001, P = 0.002, P = 0.017, P = 0.003 and P = 0.002, respectively). The use of full-course antenatal steroids, greater BW as a percentile of the Fenton curve, breastfeeding initiation and faster average velocity of weight growth effectively protected against EUGR (P = 0.008, P < 0.001, P < 0.001 and P < 0.001, respectively).ConclusionsThe overall incidence of EUGR was 43.1% among singleton-non-SGA VPIs in China. Raising the full-course antenatal steroids usage, reducing the incidence of moderate and severe BPD, attaching importance to the management of enteral nutrition in VPIs and increasing the weight growth velocity can reduce the incidence of EUGR.