Effectiveness and safety of anti-PD-1 monotherapy or combination therapy in Chinese advanced gastric cancer: A real-world study

PurposeGastric cancer (GC) is one of the most frequently diagnosed cancers and one of the leading causes of cancer deaths worldwide, especially in eastern Asia and China. Anti-PD-1 immune checkpoint inhibitors, Pembrolizumab and Nivolumab, have been approved for the treatment of locally advanced or metastatic gastric or gastroesophageal junction cancer (GC/GEJC). Our study evaluated the effectiveness and safety of anti-PD-1-based treatment (monotherapy or combination therapy) in Chinese patients with advanced or metastatic GC/GEJCs in a real-world setting.MethodsA retrospective cohort study was conducted, and 54 patients from May 31, 2015, to May 31, 2021, were included in our analysis, including 19 patients treated with anti-PD-1 monotherapy and 35 patients treated with anti-PD-1 combination therapy. Demographic and clinical information were evaluated. Clinical response, survival outcomes, and safety profile were measured and analyzed.ResultsOverall, the median overall survival (mOS) was 11.10 months (95% CI, 7.05–15.15), and the median progression-free survival (mPFS) was 3.93 months (95% CI, 2.47–5.39). Of the patients, 16.7% achieved a clinical response, and 72.2% achieved disease control. Prolonged overall survival (OS) and progression-free survival (PFS) and increased clinical response were observed in the combination group compared with the monotherapy group, although statistical significance was not reached. In subgroups with live metastases or elevated baseline neutrophil-to-lymphocyte ratio (NLR) levels, combination therapy outperformed anti-PD-1 alone in survival outcomes. Patients treated with anti-PD-1 monotherapy (n = 5, 26.3%) had fewer treatment-related adverse events (TRAEs) than those in the combination group (n = 22, 62.9%). There were also fewer patients with TRAEs of grades 3–5 with monotherapy (n = 2, 10.5%) than with combination therapy (n = 7, 20.0%). Pneumonitis in three patients was the only potential immune-related adverse event reported.ConclusionsAnti-PD-1-based monotherapy and combination therapy showed favorable survival outcomes and manageable safety profiles in advanced or metastatic GC/GEJCs. In clinical treatment, immunotherapy should be an indispensable choice in the treatment strategy for GC/GEJC. Patients with a heavy tumor burden and more metastatic sites might benefit more from combination therapy. Elderly patients and patients with more treatment lines or high Eastern Cooperative Oncology Group (ECOG) performance scores might be more suitable for immune monotherapy, and some clinical benefits have been observed

Hypericum japonicum extract inhibited porcine epidemic diarrhea virus in vitro and in vivo

Porcine epidemic diarrhea virus (PEDV) infection causes lethal watery diarrhea and high mortality in neonatal piglets, leading to huge economic losses in the global swine industry. Currently, the existing commercial vaccines cannot fully control PEDV, so it is urgent to develop effective antiviral agents to complement vaccine therapy. In the present study, we investigated the antiviral effect of Hypericum japonicum extract (HJ) against PEDV in vivo and in vitro. In in vitro assays, HJ could directly inactivate PEDV strains; moreover, it inhibited the proliferation of PEDV strains in Vero or IPI-FX cells at its non-cytotoxic concentrations. Time of addition assays revealed that HJ mainly inhibited PEDV at the later stages of the viral life cycle. In in vivo, compared with the model group, HJ could reduce the viral titers in the intestines of infected piglets, and improve their intestinal pathological, indicating that HJ could protect the newborn piglets from highly pathogenic PEDV variant infection. Furthermore, this effect may be related to the fact that HJ can not only directly inhibit viruses, but also regulate the structure of intestinal microbiota. In conclusion, our results indicate that Hypericum japonicum could inhibit PEDV replication in vitro and in vivo and might possess the potential to develop as the anti-PEDV drug

On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies

Studying the canopy spectral reflection characteristics of different N-efficient maize varieties and analyzing the relationship between their growth indicators and spectral vegetation indices can help the breeding and application of N-efficient maize varieties. To achieve the optimal management of N fertilizer resources, developing N-efficient maize varieties is necessary. In this research, maize varieties, i.e., the low-N-efficient (Zhengdan 958, ZD958), the high-N efficient (Xianyu 335, XY335), the double-high varieties (Qiule 368, QL368), and the double inefficient-type varieties (Yudan 606 YD606), were used as materials. Results indicate that nitrogen fertilization significantly increased the vegetation indices NDVI, GNDVI, GOSAVI, and RVI of maize varieties with different nitrogen efficiencies. These findings were consistent with the performance of yield, dry matter mass, and leaf nitrogen content and were also found highest under both medium and high nitrogen conditions in the double-high variety QL368. The correlations of dry matter quality, leaf nitrogen content, yield, and vegetation indices (NDVI, GNDVI, RVI, and GOSAVI) at the filling stage of different N-efficient maize varieties were all highly significant and positive. In this relationship, the best effect was found at the filling stages, with correlation coefficients reaching 0.772–0.942, 0.774–0.970, 0754–0.960, and 0.800–0.960. The results showed that the yield, dry matter weight, and leaf nitrogen content of maize varieties with different nitrogen efficiencies increased first and then stabilized with the increase in the nitrogen application level in different periods, and the highest nitrogen application level of maize yield should be between 270 and 360 kg/hm2. At the filling stage, canopy vegetation index of maize varieties with different nitrogen efficiencies was positively correlated with yield, dry matter weight, and leaf nitrogen content, especially GNDVI and GOSAVI on the leaf nitrogen content. It can be used as a means to predict its growth index

Surface charging phenomena on HVDC spacers for compressed SF6 insulation and charge tailoring strategies

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Source-reservoir rock assemblages and hydrocarbon accumulation models in the Middle-Lower Jurassic of eastern Sichuan Basin, China

The eastern Sichuan Basin in China holds vast potential for oil and gas exploration in the Lower-Middle Jurassic strata. However, the geological characteristics and hydrocarbon accumulation patterns of this region remain largely unclear. During the deposition period of the Lower-Middle Jurassic strata, the eastern Sichuan is characterized by the formation of multiple sets of source, reservoir, and caprock assemblages through depositing lake-delta-fluvial deposits, which have great exploration potential. The Jurassic source rocks in eastern Sichuan are mainly developed in the Dongyuemiao Member, Da’anzhai Member, and Liangshan Formation. These source rocks have a total organic carbon (TOC) content greater than 1 and a varying range of organic matter maturity, with a Ro value of 0.8–2.0. The kerogen in these source rocks is primarily type II, with a smaller proportion being type III. A range of reservoir rocks can be found in the Jurassic strata of eastern Sichuan, with sandstone reservoirs being predominantly found in the Liangshan Formation, Shaximiao Formation, and Zhenzhuchong Member. Shale reservoirs are mostly present in the Dongyuemiao, Da’anzhai, Liangshan, and Maanshan Members, and there is a limited distribution of limestone reservoirs in the Da’anzhai Member and Dongyuemiao Formation. The arrangement of source rocks and reservoir rocks in eastern Sichuan has led to the formation of three types of reservoir-forming combinations, including lower generation and upper storage, self-generation and self-storage, and composite. Sandstone reservoirs are typically of lower generation and upper storage, shale reservoirs are primarily of self-generation and self-storage, and limestone reservoirs are mostly composite. The exploration of Jurassic oil and gas in eastern Sichuan should prioritize “layer and area selections.” The Da’anzhai, Dongyuemiao, and Liangshan shale reservoirs should be the primary exploration targets, with the semi-deep lake deposits in the syncline area being the most favorable. The degree of fracture development in the exploration area also has a significant impact on the shale oil and gas content. The Liangshan Formation and Shaximiao Formation sandstone reservoirs can serve as secondary exploration targets, with anticline areas that have better sealing conditions being more favorable. Limestone reservoirs have limited distribution, and exploration areas with high and steep fractures are relatively more advantageous

Integrated physical, genetic and genome map of chickpea (Cicer arietinum L.)

Physical map of chickpea was developed for the reference chickpea genotype (ICC 4958) using bacterial artificial chromosome (BAC) libraries targeting 71,094 clones (~12× coverage). High information content fingerprinting (HICF) of these clones gave high-quality fingerprinting data for 67,483 clones, and 1,174 contigs comprising 46,112 clones and 3,256 singletons were defined. In brief, 574 Mb genome size was assembled in 1,174 contigs with an average of 0.49 Mb per contig and 3,256 singletons represent 407 Mb genome. The physical map was linked with two genetic maps with the help of 245 BAC-end sequence (BES)-derived simple sequence repeat (SSR) markers. This allowed locating some of the BACs in the vicinity of some important quantitative trait loci (QTLs) for drought tolerance and reistance to Fusarium wilt and Ascochyta blight. In addition, fingerprinted contig (FPC) assembly was also integrated with the draft genome sequence of chickpea. As a result, ~965 BACs including 163 minimum tilling path (MTP) clones could be mapped on eight pseudo-molecules of chickpea forming 491 hypothetical contigs representing 54,013,992 bp (~54 Mb) of the draft genome. Comprehensive analysis of markers in abiotic and biotic stress tolerance QTL regions led to identification of 654, 306 and 23 genes in drought tolerance “QTL-hotspot” region, Ascochyta blight resistance QTL region and Fusarium wilt resistance QTL region, respectively. Integrated physical, genetic and genome map should provide a foundation for cloning and isolation of QTLs/genes for molecular dissection of traits as well as markers for molecular breeding for chickpea improvement

Segregation in magnetized fluidized bed with Geldart-B magnetizable and nonmagnetizable particles

For magnetized fluidized beds with Geldart-B magnetizable and nonmagnetizable particles operated under the magnetization-LAST mode, segregation occurs and deepens as the magnetic field intensity increases. This work aimed to explore the effects of particle size and density difference on such segregation. The field intensities (His and Hcs) for the segregation to initiate and complete increased as the gas velocity (Ug) increased. Moreover, their increases were steeper at higher gas velocities. The increase of Ug raised not only the collision to the magnetic chains but also their mixing tendency with the nonmagnetizable particles. For the given nonmagnetizable particles and Ug, His and Hcs increased as the size or density of the magnetizable particles decreased, indicating that it was more difficult for the segregation to occur and complete. Additionally, the smaller/lighter the magnetizable particles, the steeper the variations of His and Hcs with Ug. A much stronger magnetic field was required for more of such magnetizable particles to form the desired magnetic chains and keep the desired size. Segregation could only be postponed but completely prevented under the magnetization-LAST operation mode however the two types of particles were matched

Effects of Two Kinds of Iron Nanoparticles as Reactive Oxygen Species Inducer and Scavenger on the Transcriptomic Profiles of Two Human Leukemia Cells with Different Stemness

Leukemia is a common and lethal disease. In recent years, iron-based nanomedicines have been developed as a new ferroptosis inducer to leukemia. However, the cytotoxicity of iron nanoparticles to leukemia cells at the transcriptomic level remains unclear. This study investigated the effects of two kinds of iron nanoparticles, 2,3-Dimercaptosuccinic acid (DMSA)-coated Fe3O4 nanoparticles (FeNPs) as a reactive oxygen species (ROS) inducer and Prussian blue nanoparticles (PBNPs) as an ROS scavenger, on the transcriptomic profiles of two leukemia cells (KG1a and HL60) by RNA-Seq. As a result, 470 and 1690 differentially expressed genes (DEGs) were identified in the FeNP-treated HL60 and KG1a cells, respectively, and 2008 and 2504 DEGs were found in the PBNP-treated HL60 and KG1a cells, respectively. Among them, 14 common upregulated and 4 common downregulated DEGs were found, these genes were representative genes that play key roles in lipid metabolism (GBA and ABCA1), iron metabolism (FTL, DNM1, and TRFC), antioxidation (NQO1, GCLM, and SLC7A11), vesicle traffic (MCTP2, DNM1, STX3, and BIN2), and innate immune response (TLR6, ADGRG3, and DDX24). The gene ontology revealed that the mineral absorption pathway was significantly regulated by PBNPs in two cells, whereas the lipid metabolism and HIF-1 signaling pathways were significantly regulated by FeNPs in two cells. This study established the gene signatures of two kinds of nanoparticles in two leukemia cells, which revealed the main biological processes regulated by the two kinds of iron nanoparticles. These data shed new insights into the cytotoxicity of iron nanoparticles that differently regulate ROS in leukemia cells with variant stemness

Estimation of Manure Emissions Issued from Different Chinese Livestock Species: Potential of Future Production

In this study, mathematical models are used to estimate the emissions of livestock excreta (LE) generated by China’s livestock industry more accurately. Also, the spatial relationship between provinces is analyzed. LE emissions are predicted for the next decade through appropriate parameters and non-parametric models. Additionally, a literature review is conducted to propose two hypotheses. As revealed by the research, there are four stages that LE emissions experience over time. From 2017 to 2021, LE emissions showed a trend of steady increase, suggesting a stronger awareness of the issue and the enforcement of more measures related to management and emission reduction. According to the results of a spatial analysis, there was no significant positive or negative correlation present between LE emissions in different provinces of China. In the selection of the prediction model, the BP-RE model achieved the best predictive performance. According to the prediction results, the fresh weight emissions from China’s livestock industry will increase by 24.53% by 2031, while dry weight emissions will decrease by 28.06%. Large-scale aquaculture farms show an upward trend, with fresh weight and dry weight emissions rising by 11.16% and 2.05%, respectively. Therefore, in light of this study’s findings, it is crucial for China to pursue additional measures in reducing LE emissions, despite the implementation of existing management policies. These insights can inform the development of livestock and poultry manure management policies and resource utilization strategies for the coming decade