The novel HLA-A*02:07:23 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*02:07:23 differs from HLA-A*02:07:01:01 by one nucleotide in exon 2.

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials.

BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

LncRNA Airsci increases the inflammatory response after spinal cord injury in rats through the nuclear factor kappa B signaling pathway.

Spinal cord injury (SCI) is a serious traumatic event to the central nervous system. Studies show that long non-coding RNAs (lncRNAs) play an important role in regulating the inflammatory response in the acute stage of SCI. Here, we investigated a new lncRNA related to spinal cord injury and acute inflammation. We analyzed the expression profile of lncRNAs after SCI, and explored the role of lncRNA Airsci (acute inflammatory response in SCI) on recovery following acute SCI. The rats were divided into the control group, SCI group, and SCI + lncRNA Airsci-siRNA group. The expression of inflammatory factors, including nuclear factor kappa B [NF-κB (p65)], NF-κB inhibitor IκBα and phosphorylated IκBα (p-IκBα), and the p-IκBα/IκBα ratio were examined 1-28 days after SCI in rats by western blot assay. The differential lncRNA expression profile after SCI was assessed by RNA sequencing. The differentially expressed lncRNAs were analyzed by bioinformatics technology. The differentially expressed lncRNA Airsci, which is involved in NF-κB signaling and associated with the acute inflammatory response, was verified by quantitative real-time PCR. Interleukin (IL-1ß), IL-6 and tumor necrosis factor (TNF-α) at 3 days after SCI were measured by western blot assay and quantitative real-time PCR. The histopathology of the spinal cord was evaluated by hematoxylin-eosin and Nissl staining. Motor function was assessed with the Basso, Beattie and Bresnahan Locomotor Rating Scale. Numerous differentially expressed lncRNAs were detected after SCI, including 151 that were upregulated and 186 that were downregulated in the SCI 3 d group compared with the control group. LncRNA Airsci was the most significantly expressed among the five lncRNAs involved in the NF-κB signaling pathway. LncRNA Airsci-siRNA reduced the inflammatory response by inhibiting the NF-κB signaling pathway, alleviated spinal cord tissue injury, and promoted the recovery of motor function in SCI rats. These findings show that numerous lncRNAs are differentially expressed following SCI, and that inhibiting lncRNA Airsci reduces the inflammatory response through the NF-κB signaling pathway, thereby promoting functional recovery. All experimental procedures and protocols were approved by the approved by the Animal Ethics Committee of Jining Medical University (approval No. JNMC-2020-DW-RM-003) on January 18, 2020.

Wu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways.

The kinase FLT3 internal tandem duplication (FLT3-ITD) is related to poor clinical outcomes of acute myeloid leukemia (AML). FLT3 inhibitors have provided novel strategies for the treatment of FLT3-ITD-positive AML. But they are limited by rapid development of acquired resistance and refractory in monotherapy. Recent evidence shows that inducing the degradation of FLT3-mutated protein is an attractive strategy for the treatment of FLT3-ITD-positive AML, especially those with FLT3 inhibitor resistance. In this study we identified Wu-5 as a novel USP10 inhibitor inducing the degradation of FLT3-mutated protein. We showed that Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC50 of 3.794, 5.056, and 8.386 µM, respectively. Wu-5 (1-10 µM) dose-dependently induced apoptosis of MV4-11, Molm13, and MV4-11R cells through the proteasome-mediated degradation of FLT3-ITD. We further demonstrated that Wu-5 directly interacted with and inactivated USP10, the deubiquitinase for FLT3-ITD in vitro (IC50 value = 8.3 µM) and in FLT3-ITD-positive AML cells. Overexpression of USP10 abrogated Wu-5-induced FLT3-ITD degradation and cell death. Also, the combined treatment of Wu-5 and crenolanib produced synergistic cell death in FLT3-ITD-positive cells via the reduction of both FLT3 and AMPKα proteins. In support of this, AMPKα inhibitor compound C synergistically enhanced the anti-leukemia effect of crenolanib, while AMPKα activator metformin inhibited the anti-leukemia effect of crenolanib. In summary, we demonstrate that Wu-5, a novel USP10 inhibitor, can overcome FLT3 inhibitor resistance and synergistically enhance the anti-AML effect of crenolanib through targeting FLT3 and AMPKα pathway.

[Current status of nitrogen and phosphorus losses and related factors in Chinese paddy fields: A review]. / æˆ‘å›½ç¨»ç”°æ°®ç£·æµå¤±çŽ°çŠ¶åŠå½±å“å› ç´ ç ”ç©¶è¿›å±•.

Rice is one of the main crops in China. Therefore, it is important to understand the current status and influencing factors of nitrogen and phosphorus losses from paddy fields in China, which would facilitate assessing the potential of chemical fertilizer reduction in different rice cultivating regions. We summarized the current knowledge on nitrogen and phosphorus losses from surface runoff in major rice cultivating areas in China, as well as their influencing factors, such as rainfall, planting pattern, cultivation techniques, fertilization management, water management strategies, etc. The total nitrogen (TN) and total phosphorus (TP) losses from runoff in six major rice cropping areas ranged from 5.09 to 21.32 and 0.70 to 3.22 kg·hm-2, respectively. The highest losses of TN and TP were the South China double rice cropping area. The TN runoff losses were the lowest in the North China single rice cropping area, while the lowest TP runoff losses occurred in plateau single and double rice cropping area of the Southwest China. The peaks of TN and TP in surface water of paddy fields were generally higher than those of the runoff water based on farmers' conventional fertilization in different rice cropping areas. The peak period of nitrogen and phosphorus losses was in a week after rice fertilization. There could be a potential of 20% reduction of nitrogen and phospho-rus for farmers' conventional fertilization compared with the optimized fertilization. Among all the factors, rainfall and fertilization management were the main ones affecting the runoff losses of nitrogen and phosphorus in paddy fields. Fertilization management and water management strategies were the mostly controllable, including reduction of fertilizers, application of new fertilizers, replacement of chemical fertilizers by organic fertilizers, water-saving irrigation, etc. Overall, the risk of nitrogen and phosphorus losses in paddy fields was more prominent in the Southern China than in any other areas of China. Rice cultivation should be carried out in a more resource-efficient way to reduce nutrient loss. Future research should focus on non-point source pollution monitoring of paddy fields, nitrogen and phosphorus losses risk assessment, nitrogen and phosphorus losses characteristics and mechanisms, and new technologies for reducing chemical fertilization inputs and environmental risks.