Global population increase will require rapid increase of food production from existing agricultural land by 2050, which will inevitably mean the increase of agricultural productivity. Due to ...agricultural sustainable intensification since the 1990s, crop production in Huantai County of northern China has risen to 15tha−1yr−1 for the annual wheat–maize rotation system. We examined the temporal dynamics of nitrogen (N) budget, N losses, and N use efficiency (NUE) during the 35years (1980–2014) in Huantai. The results revealed that atmospheric N deposition increased 220% while reactive N losses decreased by 21.5% from 1980s to 2010s. During 1980–2002, annual N partial factor productivity (PFPN), apparent NUE and N recovery efficiency (REN) increased from 20.3 to 40.7kggrainkg−1Nfert, from 36.5% to 71.0%, and from 32.4% to 57.7%, respectively; meanwhile, reactive N losses intensity, land use intensity and N use intensity decreased by 69.8%, 53.4%, 50.0%, respectively, but without further significant changes after 2002. Overall increases in NUE and decreases in N losses were largely due to the introduction of optimized fertilization practice, mechanization and increased incorporation of crop straw in Huantai. Straw incorporation was also significant in soil N stock accrual and fertility improvement. By 2030, northern China may reach the lowest end of PFPN values in developed countries (>45kggrainkg−1Nfert). These agricultural sustainable intensification practices will be critical in maintaining high grain yields and associated decreases in environmental pollution, although water use efficiency in the region still needs to be improved.
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•From 1980 to 2014 reactive N losses decreased by 21.5% in northern China.•From 1980 to 2014 annual N recovery increased from 39.8% to 54.1% at a stable yield.•Partial factor productivity may reach up to 45kggrainkg−1Nfert by 2030.•Straw return and optimized fertilization enhanced soil N stock & reduced N losses.
There is increasing evidence to suggest that the neutrophil-to-lymphocyte ratio (NLR) is related to the prognosis of patients with renal cell carcinoma (RCC) treated with immune checkpoint inhibitors ...(ICIs). However, these findings are inconsistent. The present study was performed with the aim of exploring the utility of NLR in patients with RCC treated with ICIs. For this purpose, a comprehensive search of PubMed, Web of Science, and Embase was performed to find studies evaluating the prognostic value of NLR. The overall survival (OS) and progression-free survival (PFS) were the assessed clinical outcomes. All statistical analysis was performed using Stata version 12.0 software. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) of NLR for OS and PFS were calculated using the random-effect models. Heterogeneity was evaluated based on the
value and Cochran's
test. Egger's and Begg's tests were applied to precisely assess the publication bias. The "trim and fill" method was adopted to perform the sensitivity analysis to determine whether the results were stable. In total, 12 studies encompassing 1,275 patients were included in the final analysis. The results revealed that a high NLR at baseline or pre-therapy was associated with a poor OS (HR, 2.23; 95% CI, 1.84-2.70;
< 0.001) and PFS (HR, 1.78; 95% CI, 1.72-2.09;
< 0.001). During the course of treatment, a decrease in the NLR was associated with a significantly longer OS (HR, 0.34; 95% CI, 0.20-0.56;
< 0.001) and PFS (HR, 0.44; 95% CI, 0.30-0.63;
< 0.001) compared to an increase in NLR. As a preliminary screening of other risk factors, age, sex, race, and IMDC risk may have a certain prognostic value for RCC treated with ICIs. People over 70 years old had better OS compared to people younger than 70 (HR, 0.65; 95% CI, 0.48-0.89). Non-Caucasians treated with immunotherapy had a worse OS (HR, 8.67; 95% CI, 2.87-26.2) and PFS (HR, 2.65; 95% CI, 1.28-5.48) than Caucasians. Males had a worse OS than females (HR, 1.48; 95% CI, 1.14-1.93). Compared with the IMDC favorable risk group, the OS of the IMDC poor risk group was worse (HR, 2.59; 95% CI, 1.56-4.32). There was no significant publication bias or heterogeneity observed in the present study. On the whole, the present study demonstrated that an elevated NLR is associated with an adverse OS and PFS in patients with RCC treated with ICIs. The NLR may thus be used as a readily available prognostic biomarker for these patients. Age, sex, race, and IMDC risk may have potential predictive value for the prognosis of RCC treated with ICIs. However, further investigations are warranted to validate these results.
In the wheat-maize rotation cultivation system in northern China, excessive irrigation and over-fertilization have depleted groundwater and increased nitrogen (N) losses. These problems can be ...addressed by optimized N fertilization and water-saving irrigation. We evaluated the effects of these practices on greenhouse gas emissions (GHG), net profit, and soil carbon (C) sequestration. We conducted a field experiment with flood irrigation (FN0, 0 kg N ha
yr
, FN600, 600 kg N ha
yr
) and drip fertigation treatments (DN0, 0 kg N ha
yr
; DN420, 420 kg N ha
yr
; DN600, 600 kg N ha
yr
) in 2015-2017. Compared with FN600, DN600 decreased direct GHGs (N
O + CH
) emissions by 21%, and increased the net GHG balance, GHG intensity, irrigation water-use efficiency (IWUE), and soil organic C content (ΔSOC) by 13%, 12%, 88%, and 89.8%, respectively. Higher costs in DN600 (for electricity, labour, polyethylene) led to a 33.8% lower net profit than in FN600. Compared with FN600, DN420 reduced N and irrigation water by 30% and 46%, respectively, which increased partial factor productivity and IWUE (by 49% and 94%, respectively), but DN420 did not affect GHG mitigation or net profit. Because lower profit is the key factor limiting the technical extension of fertigation, financial subsidies should be made available for farmers to install fertigation technology.
Refractory/relapsed T-cell acute lymphoblastic leukemia (R/R T-ALL) is a hematological malignancy with a poor prognosis. The current treatment strategy has not benefited most patients, and the ...treatment methods are still being explored.
An 8-year-old boy with R/R T-ALL achieved CR after multiple chemotherapies, followed by the first allo-HSCT. Unfortunately, 1 year and 3 months later, he relapsed. After recurrence, the patient underwent multiple chemotherapies, but the NOTCH1 gene and MRD were still positive. FCM and immunohistochemistry revealed abnormally high expression of CD7, so we considered bridging the second allo-HSCT after CD7 CAR T-cells treatment. The patient has low toxic and side effects and is still in CR, findings from this case report have more important therapeutic significance for R/R T-ALL.
In conclusion, CD7 CAR T-cells bridging to allo-HSCT is a safe and effective approach for R/R T-ALL, resulting in durable CR and longer survival.
•N fertilizer significantly promoted SIC dissolution in the 0–80 cm soil profile.•DMPP had no significant effect on SOC and δ13CSOC.•DMPP application slowed SIC dissolution in the 0–40 cm soil ...layer.•DMPP alleviated PIC dissolution and increased PIC stock.
In carbonate soils, soil inorganic carbon (SIC) dissolves and releases CO2 due to exogenous application of nitrogen fertilizer, which makes the soil an important carbon source. Application of the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) is likely to be an effective measure to alleviate SIC dissolution. A 5-year field experiment was conducted to observe SIC dynamics under three treatments: No N fertilizer (CK), N fertilizer (NF), and N fertilizer combined with DMPP (N + NI). Soil samples were collected from 0 to 20, 20–40, 40–60, 60–80, and 80–100 cm in depth, and soil organic carbon (SOC), SIC, total carbon (TC), total nitrogen (TN), and carbon isotope composition (δ13C) of the soil were analyzed. The proportion of pedogenic carbonate (PIC) in SIC was estimated using an isotopic mass balance equation. Results showed that: (1) compared with the application of N only, DMPP had no significant effect on SOC content and δ13CSOC in the 0–100 cm soil profile; (2) the application of N fertilizer significantly reduced the SIC content by 10.0 g·kg−1 (58.3 %) in the 0–80 cm soil profile. In the 0–20, 20–40, and 60–80 cm soil layers, the SIC content was reduced by 2.9, 1.9, and 3.8 g·kg−1, respectively. However, the SIC content significantly increased by 3.2 g·kg−1 (58.9 %) in the 80–100 cm soil layer. DMPP application significantly increased the SIC content in the 0–20 and 20–40 cm soil layers by 1.3 g·kg−1 (50.9 %) and 1.2 g·kg−1 (48.2 %), respectively; (3) DMPP combined with N significantly alleviated PIC dissolution in the 0–40 cm soil layers and increased PIC stock in 0–100 cm soil by 6.2 Mg·ha−1 (64.6 %). Applying DMPP to farmland soil containing carbonate significantly alleviated the dissolution of N fertilizer on PIC, which may decrease CO2 emissions in the field.
The use of chimeric antigen receptor T cells (CAR-Ts) is effective in the treatment of hematological malignancies. It has been reported that HBV is reactivated after CAR-T immunotherapy for ...refractory/relapsed hematological malignant B-cell tumors. However, there is little literature on donor-derived CAR-T therapy combined with allogeneic hematopoietic stem cell transplantation in hepatitis B patients with acute T-lymphocytic leukemia. We report the case of one patient with hepatitis B associated with relapsed/refractory acute T-lymphocytic leukemia (T-ALL) treated with donor-derived CD7 CAR-T therapy and allogeneic hematopoietic stem cell transplantation. During treatment, the copy number of hepatitis B virus continuously decreased, and AST, ALT, DBIL and TBIL remained within the controllable ranges. CD7-negative MRD recurred 4.5 months after transplantation, and the flow cytometry results became negative after immunosuppressive reduction. Seven months after transplantation, the patient had complete remission, and the copy number of hepatitis B virus decreased to below 10
2
. This is the first study on the safety and effectiveness of donor-derived CD7 CAR-T therapy bridging to allogeneic hematopoietic stem cell transplantation in a patient with relapsed/refractory acute T-lymphocytic leukemia and hepatitis B.
Targeting immune checkpoints, such as PD-1, represents a promising approach for cancer immunotherapy, achieving long-term disease remission rates in numerous types of cancer. T cell immunoglobulin ...and ITIM domain (TIGIT) is a checkpoint receptor associated with the antitumor roles of NK and T cells. Notably, the blockade of TIGIT has been revealed as a potential promising approach in cancer immunotherapy. However, the therapeutic potential of blocking TIGIT in myelodysplastic syndrome (MDS) remains unclear and further research is required to reveal their role.
Fresh peripheral blood (PB) and bone marrow (BM) were obtained from patients with MDS and healthy donors (HDs) at the Tianjin Medical University General Hospital between January 21 2018 and March 22 2019. The present study investigated the expression levels of TIGIT on NK and T cells using flow cytometry (FCM) and PCR. In addition, other checkpoint receptors, such as CD226 and PD-1, were also investigated. To determine the mechanisms of antitumor immunity, the functions of NK and T cells expressing TIGIT were determined.
TIGIT was found to be highly expressed on NK and T cells of the PB, where it was involved in disease progression and the immune escape of MDS. The high expression levels of TIGIT were associated with decreased NK and T cell function, and significantly lower secretions of activation factors, such as CD107a, IFN-γ and TNF-α. Notably, blocking TIGIT enhanced the antitumor effects of NK and T cells.
The results of the present study suggested that targeting TIGIT alone or in combination with PD-1 may be a promising anticancer therapeutic strategy in MDS.
Selecting proper postoperative adjuvant therapy is of great importance for prolonging overall survival (OS) of patients with biliary tract cancer (BTC). OS is commonly affected by high rate of ...postoperative recurrence and metastasis.
The present study aimed to identify the optimal adjuvant therapy for BTC patients.
A comprehensive search was carried out on Pubmed, Web of science, and Embase databases to acquire articles regarding BTC therapy approaches. Subsequently, the hazard ratio (HR) and its 95% confidence intervals (CIs) were applied to evaluate the efficacy of different adjuvant therapy regimens. The GemTc (GemTc.0.8-2) and R (R.3.6.0) software were employed to perform statistical analyses.
Data from 22 articles, including 14,646 patients, were quantitatively analyzed. The results showed that in terms of 5-year OS, gemcitabine (GEM) was considered as the optimal adjuvant therapy for BTC compared with chemoradiotherapy (CRT; HR = 0.59; 95% CI = 0.34-0.97), observation (OB; HR = 0.49; 95% CI = 0.33-0.73), and radiotherapy (RT; HR = 0.40; 95% CI = 0.22-0.71). Additionally, 5-fluorouracil (5-FU) exhibited improved efficacy compared with RT (HR = 0.52; 95% CI = 0.29-0.91) and OB (HR = 0.63; 95% CI = 0.43-0.92). When the efficacy of 5-FU was compared with that of GEM, the results showed that 5-FU (HR = 1.29) was more effective than GEM. Furthermore, CRT and RT prolonged positive resection margin (R
)-OS (HR = 0.69; 95% CI = 0.49-1.00) and positive lymph node-(N
)-OS (HR = 0.22; 95% CI = 0.074-0.66) in BTC patients. In terms of median recurrence-free survival (RFS) and 1-year OS, the differences were not statistically significant among different therapeutic interventions.
The present study suggested that GEM could be used as a first-line adjuvant therapy for resected BTC patients. Additionally, CRT could be the optimal treatment approach for R
and N
patients.
Many studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This ...meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS.
A full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3.
This meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47-0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36-0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI: 0.41-0.83, P = 0.003) and 0.6 (95% CI: 0.37-0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI: 0.45-0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed.
Thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.
•Dynamic substance flow analysis highlight nutrient imbalances.•Revealed divergence of farm practice, fertiliser recommendations and best practice•Specific improvements in nutrient management for ...different systems are required.•Systemic analysis at county scale matches relevant decision making and policy.•Advice can be tailored drawing from readily available information.
In order to improve the efficiency of nutrient use whilst also meeting projected changes in the demand for food within China, new nutrient management frameworks comprised of policy, practice and the means of delivering change are required. These frameworks should be underpinned by systemic analyses of the stocks and flows of nutrients within agricultural production. In this paper, a 30-year time series of the stocks and flows of nitrogen (N), phosphorus (P) and potassium (K) are reported for Huantai county, an exemplar area of intensive agricultural production in the North China Plain. Substance flow analyses were constructed for the major crop systems in the county across the period 1983–2014. On average across all production systems between 2010 and 2014, total annual nutrient inputs to agricultural land in Huantai county remained high at 18.1kt N, 2.7kt P and 7.8kt K (696kg N ha−1; 104kgP ha−1; 300kgK ha−1). Whilst the application of inorganic fertiliser dominated these inputs, crop residues, atmospheric deposition and livestock manure represented significant, yet largely unrecognised, sources of nutrients, depending on the individual production system and the period of time. Whilst nutrient use efficiency (NUE) increased for N and P between 1983 and 2014, future improvements in NUE will require better alignment of nutrient inputs and crop demand. This is particularly true for high-value fruit and vegetable production, in which appropriate recognition of nutrient supply from sources such as manure and from soil reserves will be required to enhance NUE. Aligned with the structural organisation of the public agricultural extension service at county-scale in China, our analyses highlight key areas for the development of future agricultural policy and farm advice in order to rebalance the management of natural resources from a focus on production and growth towards the aims of efficiency and sustainability.
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