Objective: To observe the effect of liquid paraffin as adjuvant therapy in treating residual wounds of patients with severe burns. Methods: From January 2016 to October 2017, 58 patients with residual wounds in the later stage of severe burns were admitted to Beijing Jishuitan Hospital. Those patients met the inclusion criteria of this study and were enrolled in this retrospective cohort study. All the patients received wound disinfection, petrolatum gauze dressing change and silver ion-bearing antimicrobial dressing every other day to treat the residual wound until wound healing. From January to November 2016, 29 patients who were treated with iodophor and normal saline to clean and disinfect the wound before dressing change were enrolled in normal saline group, including 22 males and 7 females, aged (38±12) years. From December 2016 to October 2017, 29 patients who were treated with iodophor and liquid paraffin to clean and disinfect the wound before dressing change were enrolled in liquid paraffin group, including 20 males and 9 females, aged (37±12) years. The effective rate of treatment, infection control rate, and bacterial positive ratio of wound on post first treatment day (PFTD) 7, 14, and 21 and the complete wound healing time of patients were compared between the two groups. Data were statistically analyzed with independent sample t test, Wilcoxon rank-sum test, chi-square test, and Pearson chi-square test, continuity correction chi-square test, and Fisher's exact probability test after Bonferroni correction. Results: (1) On PFTD 7, 14, and 21, the effective rates of wound treatment in patients of liquid paraffin group were 34% (10/29), 59%(17/29), and 79%(23/29), respectively, which were significantly higher than 10% (3/29), 24% (7/29), and 38% (11/29) of normal saline group (χ(2)=5.857, 7.108, 10.235, P<0.05 or P<0.01). (2) The wound infection control rates in patients of liquid paraffin group on PFTD 7 and 14 were 79% (23/29) and 90% (26/29), respectively, which were significantly higher than 31% (9/29) and 52% (15/29) of normal saline group (χ(2)=13.663, 8.321, P<0.01). The wound infection control rate in patients of liquid paraffin group on PFTD 21 was 100% (29/29), which was significantly higher than 69% (20/29) of normal saline group (P<0.01). (3) The bacterial positive ratios in the wounds of liquid paraffin group were similar to those of normal saline group on PFTD 7 and 14 (χ(2)=2.097, 2.583, P>0.05). On PFTD 21, the wound bacterial positive ratio of liquid paraffin group was 8% (3/39), which was significantly lower than 49% (17/35) of normal saline group (χ(2)=13.625, P<0.01). (4) The complete wound healing time of patients in liquid paraffin group was 15.0 (11.0, 20.0) d, which was significantly shorter than 22.0 (15.0, 27.5) d of normal saline group (Z=2.256, P<0.05). Conclusions: In the treatment of residual wounds of severe burn patients, liquid paraffin as adjuvant therapy can effectively improve the treatment effective rate and the infection control rate of wounds, decrease the bacterial positive ratio, and shorten the wound healing time.目的： 观察液体石蜡辅助治疗重度烧伤患者残余创面的效果。 方法： 2016年1月—2017年10月，北京积水潭医院收治的58例重度烧伤后期残余创面患者符合本研究入选标准，对其进行回顾性队列研究。患者均采用隔日消毒、更换油纱及银离子抗菌敷料的方法进行残余创面的治疗，直至创面愈合。2016年1—11月收治的29例患者更换敷料前使用碘伏和生理盐水清洗消毒创面，设为生理盐水组，其中男22例、女7例，年龄(38±12)岁；2016年12月—2017年10月收治的29例患者更换敷料前使用碘伏及液体石蜡清洗消毒创面，设为液体石蜡组，其中男20例、女9例，年龄(37±12)岁。比较2组患者首次治疗后7、14、21 d创面治疗有效率、创面感染控制率、创面细菌阳性比，创面完全愈合时间。对数据行两独立样本t检验、Wilcoxon秩和检验、χ(2)检验及Bonferroni校正后的Pearson χ(2)检验、连续性校正χ(2)检验及Fisher确切概率法检验。 结果： (1)首次治疗后7、14、21 d，液体石蜡组患者创面治疗有效率分别为34%(10/29)、59%(17/29)、79%(23/29)，明显高于生理盐水组的10%(3/29)、24%(7/29)、38%(11/29)，χ(2)＝5.857、7.108、10.235，P<0.05或P<0.01。(2)液体石蜡组患者首次治疗后7、14 d创面感染控制率分别为79%(23/29)、90%(26/29)，明显高于生理盐水组的31%(9/29)、52%(15/29)，χ(2)＝13.663、8.321，P<0.01；首次治疗后21 d创面感染控制率为100%(29/29)，明显高于生理盐水组的69%(20/29)，P<0.01。(3)液体石蜡组患者首次治疗后7、14 d创面细菌阳性比与生理盐水组相近(χ(2)＝2.097、2.583，P>0.05)；首次治疗后21 d创面细菌阳性比为8%(3/39)，明显低于生理盐水组的49%(17/35)，χ(2)＝13.625，P<0.01。(4)液体石蜡组患者创面完全愈合时间为15.0(11.0，20.0)d，明显短于生理盐水组的22.0(15.0，27.5)d，Z＝2.256，P<0.05。 结论： 采用液体石蜡辅助治疗严重烧伤患者残余创面，可以有效提高创面治疗有效率及感染控制率，降低创面细菌阳性比，缩短创面愈合时间。.
Fumonisin B1 (FB1) is a common mycotoxin contamination in agricultural commodities being considered as a significant risk to human and livestock health, while the mechanism of FB1 immunotoxicity are less understood, especially in chicken. Given that extracellular traps as a novel defense mechanism of leukocytes play an important role against foreign matters, in this study we aimed to investigate the effects of FB1 on chicken heterophil extracellular traps (HETs) formation. Our result showed that FB1 induced HETs release in chicken heterophils observed via immunostaining, and it was concentration-dependent during 10 to 40 μM. Moreover, in 40 μM FB1-exposed chicken heterophils, reactive oxygen species (ROS) level was increased, while catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity and glutathione (GSH) content were decreased. Simultaneously, FB1 (40 μM) activated ERK and p38 MAPK signaling pathways via increasing the phosphorylation level of ERK and p38 proteins. However, pretreatment of SB202190, U0126, and diphenyleneiodonium chloride (DPI) did not change FB1-triggered ROS production and HETs formation, suggesting FB1-induced HETs was a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38, and extracellular regulated protein kinases (ERK) signaling pathways-independent process. Inhibition of peptidyl arginine deiminase 4 (PAD4) enzyme and P2 × 1 receptor showed their vital role in 40 μM FB1-triggered HETs. This study reported for the first time that 40 μM FB1 induced the release of HETs in heterophils, and it was related to ROS production, PAD4, and P2 × 1, but was independent of NADPH oxidase, p38 and ERK signaling pathways, which might provide a whole novel perspective of perceiving and understanding the role of FB1 in immunotoxicity.
Objectives To evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival. Materials and methods A total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-β, and the infiltration density of CD3 + TILs and CD8 + TILs. The correlation between the expression of STING, PD-L1, IFN-β and the infiltration density of CD3 + TILs and CD8 + TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed. Results NACT increased the expression of STING, IFN-β and PD-L1 in tumor cells, and the infiltration of CD3 + and CD8 + TILs. In addition, ypTNM stage, ypN stage, changes in CD3 + TILs and in PD-L1 were associated with DFS (disease-free survival). CD3 + TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3 + TILs changes were independent prognostic factors for DFS and OS. Conclusion NACT stimulates STING/IFN-β pathway, promotes infiltration of CD3 + and CD8 + TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3 + TILs after NACT. Patients with ypN0 and elevated CD3 + TILs after NACT had better OS benefits.
Pancreatic ductal adenocarcinoma (PDAC) is radioresistant. Due to their strong X-ray absorption capacity, gold nanoparticles (AuNPs) have been used as radiosensitizers for cancer therapeutics. Herein, we describe a novel conjugate complex consisting of a peptide for targeting plectin-1 (PTP) specifically expressed on the PDAC cell membrane and AuNPs, termed AuNP-PTP, to be used for PDAC radiotherapy in vitro and in vivo. Previous studies revealed that compared with unmodified AuNPs, AuNP-PTP along with relevant low-energy X-ray irradiation of 6 MV at a dose of 2 Gy (RF) increased the targeting efficiency and induced apoptosis in treated PANC-1 cells and tumours. Importantly, extensive histopathological examination did not reveal evidence of acute or chronic injury in mice due to AuNPs or AuNP-PTP for up to six weeks despite the presence of X-ray exposure. The delicate AuNP-PTP hybrid provides a novel strategy to enhance radiotherapy efficiency in PDAC treatment.
Titanium dioxide nanoparticles (nTiO2) play a critical role in promoting allergic airway inflammation, but the mechanism underlying in the immune response remains not well clarified. Extracellular traps (ETs) formation has been proved to be associated with exacerbation pathogenesis of allergic asthma. Thus, we aimed to investigate whether nTiO2 aggravated allergic asthma responses via ETs formation, and the potential molecule mechanism of these actions in nTiO2 aggravated allergic asthma response. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected for histologic analysis, cytokine examining and NETs quantitation. Morphologic quantitative analysis of nTiO2-induced ETs was observed by fluorescence confocal microscopy. The results showed that nTiO2 administration induced severe pathological features of allergic asthma responses and IL-4 and IL-13 levels than OVA. Furthermore, nTiO2 promoted pulmonary ETs release in OVA-induced allergic asthma, which was degraded by DNase I. Besides adjuvant effects of nTiO2 in OVA-induced allergic asthma, nTiO2 also directly induced ETs release in vivo and in vitro, which reveal that nTiO2 may also directly induced immune responses through ETs formation. All these results suggest that strategies against ETs release might be helpful for treatment of nTiO2-provoted inflammatory response in OVA-induced allergic asthma.
Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.
Respirovirus infection can cause viral pneumonia and acute lung injury (ALI). The interleukin-1 (IL-1) family consists of proinflammatory cytokines that play essential roles in regulating immune and inflammatory responses in vivo. IL-1 signaling is associated with protection against respiratory influenza virus infection by mediation of the pulmonary anti-viral immune response and inflammation. We analyzed the infiltration lung immune leukocytes and cytokines that contribute to inflammatory lung pathology and mortality of fatal H1N1 virus-infected IL-1 receptor 1 (IL-1R1) deficient mice. Results showed that early innate immune cells and cytokine/chemokine dysregulation were observed with significantly decreased neutrophil infiltration and IL-6, TNF-α, G-CSF, KC, and MIP-2 cytokine levels in the bronchoalveolar lavage fluid of infected IL-1R1-/- mice in comparison with that of wild type infected mice. The adaptive immune response against the H1N1 virus in IL-1R1-/- mice was impaired with downregulated anti-viral Th1 cell, CD8+ cell, and antibody functions, which contributes to attenuated viral clearance. Histological analysis revealed reduced lung inflammation during early infection but severe lung pathology in late infection in IL-1R1-/- mice compared with that in WT infected mice. Moreover, the infected IL-1R1-/- mice showed markedly reduced neutrophil generation in bone marrow and neutrophil recruitment to the inflamed lung. Together, these results suggest that IL-1 signaling is associated with pulmonary anti-influenza immune response and inflammatory lung injury, particularly via the influence on neutrophil mobilization and inflammatory cytokine/chemokine production.
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