Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy ...(nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596).
A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28, with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802).
NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
•The CMISG1701 trial assessed the safety and efficacy of nCRT versus nCT followed by MIE for locally advanced bulky ESCC.•The nCRT followed by MIE strategy could not improve survival significantly compared with the nCT strategy.•The best strategy of neoadjuvant therapy for locally advanced bulky ESCC remains a pending issue.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intensive vegetable cultivation has developed very rapidly in China, and investigation of current soil nutrient problems in vegetable fields and their potential environmental risk is important for ...local soil nutrient management strategies. Three hundred and sixty‐six soil samples were collected from greenhouse vegetable fields, open vegetable fields and rice/wheat rotation fields in southern Jiangsu Province, the most intensive vegetable‐producing areas in Yangtze River Delta, China, for the analysis of their soil fertility status. Soil acidification and P enrichment were the main problems identified in this area of vegetable production, with about 20 and 17% of the open and greenhouse vegetable field soils, respectively, being extremely acid with soil pH values below 5.0. In contrast, no soils under rice/wheat rotation fields were as acidic. Percentages of sites with Olsen‐P concentrations < 90 mg/kg were 61, 85 and 0% for soils growing greenhouse vegetable, field vegetable and rice/wheat, respectively. The nitrogen (N) surplus for vegetable fields exceeded 170 kg/ha/crop, and the phosphorus (P) surplus exceeded 40 kg/ha/crop. Thus, current vegetable production leads to potential environmental risks of N and P pollution of nearby aquatic bodies. Insufficient supplementation with potassium fertilizers was found in some vegetable fields. Several ameliorative measures are proposed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Our understanding of the global aerosol change is rather limited, although it is well known that aerosol forcing could affect the global radiative budget, hydrological processes, carbon, nitrogen and ...sulfur cycles, as well as climate change. To understand the wide range effects of aerosols, it is key to obtain aerosol characteristics at high spatio-temporal resolutions. In this study, we try to map the global variations of the aerosol optical depth (AOD) using two aerosol products retrieved from MODIS (Moderate Resolution Imaging Spectroradiometer) satellite instrument. It is found that the global average AOD is 0.126 over the last decade (2003–2012). The highest and the lowest AOD occurred in 2007 and 2010, respectively. AOD variations between land and ocean, north and south hemispheres, among seven continents and four oceans were also explored. It is interesting to find that high concentrations of aerosols are mainly distributed in regions where developing countries are located (Asia and Africa), and an increasing trend could also be observed. Seasonal variations of AOD (air quality) can also be noted, which is decreasing in the north hemisphere from spring, summer to autumn and winter, but increasing in the south hemisphere.
•Global aerosol change in different regions in the last decade.•Which year is the highest or lowest of aerosols in different regions.•Where are the aerosols decreasing or increasing.•The aerosol changes with seasons in northern and southern hemisphere.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Anaesthesia/surgery altered the gut microbiome in aged mice.•Dysbacteriosis induced by anaesthesia/surgery impaired reference memory in aged mice.•Probiotics alleviated reference memory impairment ...induced by anaesthesia/surgery.
Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD.
Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice.
The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics.
Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases (HDAC) are important regulators to maintain chromatin ...structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells. Using genetic and pharmacological approaches, we show that HDAC3 contributes to chemotherapy resistance by regulating the activation of AKT, a well-documented factor in drug resistance development. HDAC3 binds to AKT and deacetylates it at the site Lys20, thereby promoting the phosphorylation of AKT. Chemotherapy drug exposure enhances the interaction between HDAC3 and AKT, resulting in decrease in AKT acetylation and increase in AKT phosphorylation. Whereas HDAC3 depletion or inhibition abrogates these responses and meanwhile sensitizes leukemia cells to chemotoxicity-induced apoptosis. Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9
leukemia to chemotherapy. Our findings suggest that combination therapy with HDAC3 inhibitor and genotoxic agents may constitute a successful strategy for overcoming chemotherapy resistance.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Galectin-1 (Gal-1) is involved in several pathological activities associated with tumor progression and chemoresistance, however, the role and molecular mechanism of Gal-1 activity in hepatocellular ...carcinoma (HCC) epithelial-mesenchymal transition (EMT) and sorafenib resistance remain enigmatic. In the present study, forced Gal-1 expression promoted HCC progression and sorafenib resistance. Gal-1 elevated αvβ3-integrin expression, leading to AKT activation. Moreover, Gal-1 overexpression induced HCC cell EMT via PI3K/AKT cascade activation. Clinically, our data revealed that Gal-1 overexpression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that Gal-1 may be a potential therapeutic target for HCC and a biomarker for predicting response to sorafenib treatment.
Necrotizing enterocolitis (NEC) is one of the most severe complications in very preterm infants, but there are currently no accepted methods to prevent NEC. Studies have shown that erythropoietin ...(EPO) has the potential to prevent NEC or improve outcomes of preterm NEC. This study aimed to determine whether recombinant human EPO (rhEPO) could protect against NEC in very preterm infants.
The study was a prospective randomized clinical trial performed among four NICU centers. A total of 1327 preterm infants with gestational age ≤ 32 weeks were admitted to the centers, and 42 infants were excluded leaving 1285 eligible infants to be randomized to the rhEPO or control group. Infants in the rhEPO group were given 500 IU/kg rhEPO intravenously every other day for 2 weeks, while the control group was given the same volume of saline. The primary outcome was the incidence of NEC in very preterm infants at 36 weeks of corrected gestational age.
A total of 1285 infants were analyzed at 36 weeks of corrected age for the incidence of NEC. rhEPO treatment significantly decreased the incidence of NEC (stage I, II and III) (12.0% vs. 17.1%, p = 0.010), especially confirmed NEC (stage II and III) (3.0% vs. 5.4%, p = 0.027). Meanwhile, rhEPO treatment significantly reduced the number of red blood cells transfusion in the confirmed NEC cases (1.2 ± 0.4 vs. 2.7 ± 1.0, p = 0.004). Subgroup analyses showed that rhEPO treatment significantly decreased the incidence of confirmed NEC at gestational age < 28 weeks (p = 0.019), and the incidence of all stages NEC in preterm infants with hemoglobin < 90 g/l (p = 0.000) and 5 min Apgar score > 5 (p = 0.028).
Repeated low-dose rhEPO treatment is beneficial against NEC in very preterm infants. Trial registration The protocol was registered retrospectively at ClinicalTrials.gov (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A thermal cloak can hide an object inside the cloak from the detection by measuring external heat flow (outside the cloak); this behavior is called the cloaking effect. However, such a thermal cloak ...has a limitation. Namely, the object is always located inside the cloak’s central region with a homogeneous temperature distribution, and hence this object cannot feel the flow of heat. To overcome the limitation, we develop a coordinate transformation method to design a complementary material, and add it into the central region of the cloak. As a result of finite element simulations, in case of external heat flow, the temperature distribution in this central region becomes inhomogeneous and hence the object feels the flow of heat indeed. Meanwhile, the cloaking effect remains the same, or almost the same as the cloak without such a complementary material inside. Thus, it becomes possible to use complementary materials to design thermal devices where heat conduction can be controlled at will.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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