Discovery of SILA-123 as a Highly Potent FLT3 Inhibitor for the Treatment of Acute Myeloid Leukemia with Various FLT3 Mutations.

The FLT3-ITD (internal tandem duplication) mutant has been a promising target for acute myeloid leukemia (AML) drug discovery but is now facing the challenge of resistance due to point mutations. Herein, we have discovered a type II FLT3 inhibitor, SILA-123. This inhibitor has shown highly potent inhibitory effects against FLT3-WT (IC50 = 2.1 nM) and FLT3-ITD (IC50 = 1.0 nM), tumor cells with the FLT3-ITD mutant such as MOLM-13 (IC50 = 0.98 nM) and MV4-11 (IC50 = 0.19 nM), as well as BaF3 cells associated with the FLT3-ITD mutant and point mutations like BaF3-FLT3-ITD-G697R (IC50 = 3.0 nM). Moreover, SILA-123 exhibited promising kinome selectivity against 310 kinases (S score (10) = 0.06). In in vivo studies, SILA-123 significantly suppressed the tumor growth in MV4-11 (50 mg/kg/d, TGI = 87.3%) and BaF3-FLT3-ITD-G697R (50 mg/kg/d, TGI = 60.0%) cell-inoculated allograft models. Our data suggested that SILA-123 might be a promising drug candidate for FLT3-ITD-positive AML.

A new three-dimensional barium(II) coordination polymer constructed from N,N'-bis(glycinyl)pyromellitic diimide: microwave-assisted synthesis, structure, Hirshfeld surface analysis and properties.

A new three-dimensional (3D) coordination polymer, namely, poly[diaqua[µ5-2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetato]barium(II)], [Ba(C14H6N2O8)(H2O)2]n, (I), has been synthesized by the microwave-irradiated reaction of Ba(NO3)2 with N,N'-bis(glycinyl)pyromellitic diimide {BGPD, namely, 2,2'-(1,3,5,7-tetraoxo-1,2,3,5,6,7-hexahydropyrrolo[3,4-f]isoindole-2,6-diyl)diacetatic acid, H2L}. The title compound was structurally characterized by single-crystal X-ray diffraction analysis and powder X-ray diffraction analysis, as well as IR spectroscopy. In the crystal structure of (I), the BaII ion is nine-coordinated by six carboxylate O atoms from five symmetry-related L2- dianions and one imide O atom, as well as two water O atoms. The coordination geometry of the central BaII ion can be described as a spherical capped square antiprism. One carboxylate group of the ligand serves as a µ3-bridge linking the BaII cations into a one-dimensional polynuclear secondary building unit (SBU). Another carboxylate group of the ligand acts as a µ2-bridge connecting the 1D SBUs, thereby forming a two-dimensional (2D) SBU. The resulting 2D SBUs are extended into a 3D framework via the pyromellitic diimide moiety of the ligand as a spacer. The 3D Ba framework can be simplified as a 5-connected hexagonal boron nitride net (bnn) topology. The intermolecular interactions in the 3D framework were further investigated by Hirshfeld surface analysis and the results show that the prominent interactions are H...O (45.1%), Ba...O (11.1%) and C...H (11.1%), as well as H...H (11.1%) contacts. The thermal stability, photoluminescence properties and UV-Vis absorption spectra of (I) were also investigated. The coordination polymer exhibits a fluorescence emission with a quantum yield of 0.071 and high thermal stability.

Disease burden of AIDS in last 30-year period and its predicted level in next 25-years based on the global burden disease 2019.

BACKGROUND: This study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years. METHODS: Comprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model. RESULTS: From 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender. CONCLUSIONS: The global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and < 15 years old. This underscores the urgent need for increased resources to combat AIDS in this region, with focused attention on protecting women and < 15 years old as priority groups. The AIDS epidemic remained severe in sub-Saharan Africa. Projections for the next 25 years indicate a substantial and ongoing decline in both age-standardized incidence and mortality rates.

May Measurement Month 2021: an analysis of blood pressure screening results from China.

We reported findings from participants screened during the May Measurement Month 2021 in China, which aimed to raise awareness of raised blood pressure (BP), and to investigate the risk factors of BP. The study participants were adults (≥18 years), ideally in whom BP had not been measured in the previous year. Blood pressure was measured three times consecutively with 1 min intervals in the sitting position, using a validated upper-arm cuff automated BP monitor (Omron HEM-7081IT), and transmitted to a central cloud database via a smartphone app. The measurement was performed in 218 844 participants in 183 sites across 31 China provinces. The mean (standard deviation) age was 47.0 (15.7) years, and 51.8% (n = 113 466) were women. The mean systolic/diastolic BP was 120.2/77.5 mmHg. Among 57 178 (26.1%) participants with hypertension, the awareness, treatment, and control rates of hypertension were 30.4% (n = 17 354), 28.7% (n = 16 369), and 17.1% (n = 9743), respectively. After adjustment for age, sex, and use of antihypertensive medication, both systolic and diastolic BP were significantly (P ≤ 0.01) higher in current smokers (n = 22 344, +0.4/+0.7 mmHg) and with moderate (n = 4780, +1.4/+4.2 mmHg) or daily alcohol intake (n = 2427, +1.3/+2.5 mmHg). Blood pressure was lower in those reporting regular exercise (n = 32 328, -2.2/-1.4 mmHg). In addition, individuals with previous COVID-19 vaccination had lower systolic and diastolic BP (n = 88 945, -1.8/-1.5 mmHg, P ≤ 0.001). In conclusion, our study showed that long-term large-scale screening for hypertension is feasible, and there is a strong association between BP and major lifestyle factors.

ARTN-GFRA3 axis induces epithelial-mesenchymal transition phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.

Neural invasion underlies the local spread of gastric cancer and is associated with poor prognosis. This process has been receiving increasing attention in recent years. However, the relationship between neural invasion and the malignant phenotypes of gastric cancer cells, as well as the molecular mechanism involved in this process, remain unclear. In this study, bioinformatics analysis was performed using a dataset obtained from The Cancer Genome Atlas-Stomach Adenocarcinoma. The results revealed that high expression of GDNF family receptor alpha 3 (GFRA3) was associated with a poor prognosis of patients with gastric cancer. GFRA3 is a receptor for artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF). This association was indicated by short overall/disease-free survival, as well as the presence of high-stage and high-grade disease. Gene set enrichment analysis showed that two cancer-associated pathways, namely KRAS signaling and epithelial-mesenchymal transition (EMT), were activated when GFRA3 was highly expressed in gastric cancer. Further studies confirmed that GFRA3 activated KRAS downstream signaling phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) or extracellular signal-regulated kinase (ERK) and induced EMT markers, as well as promoted the migration and invasion of gastric cancer cells. As a ligand of GFRA3, ARTN induced the EMT, migration, and invasion of gastric cancer cells via GFRA3. Notably, the effects of the ARTN-GFRA3 axis were attenuated by treatment with a KRAS inhibitor. The present findings indicated that, during the neural invasion of gastric cancer, ARTN-mediated activation of GFRA3 induces EMT phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.

Discovery of RORγ Allosteric Fluorescent Probes and Their Application: Fluorescence Polarization, Screening, and Bioimaging.

Retinoic acid receptor-related orphan receptor γ (RORγ) acts as a crucial transcription factor in Th17 cells and is involved in diverse autoimmune disorders. RORγ allosteric inhibitors have gained significant research focus as a novel strategy to inhibit RORγ transcriptional activity. Leveraging the high affinity and selectivity of RORγ allosteric inhibitor MRL-871 (1), this study presents the design, synthesis, and characterization of 11 allosteric fluorescent probes. Utilizing the preferred probe 12h, we established an efficient and cost-effective fluorescence polarization-based affinity assay for screening RORγ allosteric binders. By employing virtual screening in conjunction with this assay, 10 novel RORγ allosteric inhibitors were identified. The initial SAR studies focusing on the hit compound G381-0087 are also presented. The encouraging outcomes indicate that probe 12h possesses the potential to function as a powerful tool in facilitating the exploration of RORγ allosteric inhibitors and furthering understanding of RORγ function.

Design and synthesis 1H-Pyrrolo[2,3-b]pyridine derivatives as FLT3 inhibitors for the treatment of Acute myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1H-pyrrolo[2,3-b]pyridine derivatives CM1-CM24, as FLT3 inhibitors based on F14, which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 µΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3-ITD mutant), with IC50 values of 0.75 µM and 0.64 µM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3-ITD mutations.

Right paraduodenal hernia, classification, and selection of surgical methods: a case report and review of the literature.

BACKGROUND: Considering that right paraduodenal hernia is a rare internal hernia with abnormal anatomy and is often encountered during an emergency, surgeons may lack knowledge about it and choose incorrect treatment. Thus, this case report is a helpful complement to the few previously reported cases of right paraduodenal hernia. Additionally, we reviewed all the reported right paraduodenal hernia cases and proposed appropriate surgical strategies according to different anatomical features. CASE PRESENTATION: The case involved a 33-year-old Chinese male patient who was admitted to the hospital due to abdominal pain. The patient was initially diagnosed with small bowel obstruction, and conservative treatment failed. An emergency operation was arranged, during which a diagnosis of right paraduodenal hernia was made instead. After surgery, the patient recovered well without abdominal pain for 2 years. CONCLUSION: Although right paraduodenal hernia accounts only for a small proportion of paraduodenal hernia, its anatomical characteristics can vary considerably. We divided right paraduodenal hernia into three types, with each type requiring a different surgical strategy.

Micro-simulation insights into the functional and mechanistic understanding of glycyrrhizin against asthma.

Asthma is a common chronic respiratory disease, which causes inflammation and airway stenosis, leading to dyspnea, wheezing and chest tightness. Using transgelin-2 as a target, we virtually screened the lead compound glycyrrhizin from the self-built database of anti-asthma compounds by molecular docking technology, and found that it had anti-inflammatory, anti-oxidative and anti-asthma pharmacological effects. Then, molecular dynamics simulations were used to confirm the stability of the glycyrrhizin-transgelin-2 complex from a dynamic perspective, and the hydrophilic domains of glycyrrhizin was found to have the effect of targeting transgelin-2. Due to the self-assembly properties of glycyrrhizin, we explored the formation process and mechanism of the self-assembly system using self-assembly simulations, and found that hydrogen bonding and hydrophobic interactions were the main driving forces. Because of the synergistic effect of glycyrrhizin and salbutamol in improving asthma, we revealed the mechanism through simulation, and believed that salbutamol adhered to the surface of the glycyrrhizin nano-drug delivery system through hydrogen bonding and hydrophobic interactions, using the targeting effect of the hydrophilic domains of glycyrrhizin to reach the pathological parts and play a synergistic anti-asthmatic role. Finally, we used network pharmacology to predict the molecular mechanisms of glycyrrhizin against asthma, which indicated the direction for its clinical transformation.

Geochemical behaviors of uranium and thorium during weathering and pedogenesis of carbonate rock: constraint from their speciation.

During weathering and pedogenesis of carbonate rock with poor-uranium (U) and thorium (Th), U and Th present the characteristics of strong leaching (especially U) and significant residual enrichment, the cause of which is still unclear. In this paper, a weathering profile developed by dolomite in karst area of Guizhou province in southwest China was selected, which showed zonation characteristics of bedrock (Y), powdery rock (Yf), and soil layer (T1 to T12) from the bottom to up. Through the determination of the occurrence speciation of U and Th in Y and weathering profile, combined with mineralogical, geochemical characteristics, and element mass balance calculation, the constraints of U and Th speciation on the geochemical behavior of U and Th during the weathering of carbonate rock were revealed. The results proved that U and Th in Y preferentially existed in acid insoluble phase, for example, the contents of U and Th in Y were 0.90 mg·kg-1 and 0.28 mg·kg-1, respectively, while those in acid insoluble matter were 2.34 mg·kg-1 and 2.57 mg·kg-1, respectively, but because the mass percentage of acid insoluble matter was extremely low (0.95%), the mass percentages of U and Th in the acid soluble phase in the whole rock were absolutely superior (96% of U and 86% Th). The U and Th in the acid soluble phase of Y were mainly adsorbed on the crystal surface of carbonate minerals or existed in the cement, and the U and Th in the carbonate lattice only accounted for a small proportion. From Y to Yf with the initial dissolution, U and Th released from the surface of carbonate minerals and cements were in carbonate-rich alkaline environment, and these portions of U and Th were leached out, resulting in strong loss of U and Th in the Yf (the loss rates are 83% of U and 65% of Th, respectively). From the Yf to the overlying soil layer T1, the carbonate components were completely dissolved, and the U and Th released from the carbonate lattice showed different behaviors, where U was completely leached and Th tended to stay in the weathered residue. Thus, in the soil layer T1 formed by Y or Yf , the residual U was the inheritance of the U in the acid insoluble phase of Y; For Th, it not only inherited the Th of acid insoluble phase of Y, but also superimposed the Th from carbonate lattice in Y. On the other hand, during the evolution process from Y to Yf and to soil layer T1, with the dissolution of carbonate, the acid insoluble phase also showed a significant tendency of chemical weathering. However, the U and Th in the Y acid insoluble phase were not leached with the decomposition of the acid insoluble phase but were redistributed among the residual phases. For the geochemical behaviors of U and Th in the evolution of soil profile (T1~T12), they were subjected to the occurrence speciation of U and Th in T1 and the change of U and Th occurrence speciation with the upward direction of soil profile. The U and Th released from the carrier minerals were mainly redistributed among the residual solid phases, which weakened the intensity of their further loss. This study deepens the understanding of the geochemical behavior of radionuclides in karst environment and provides reference for the treatment of radioactive pollution in karst areas.

Physiological and Transcriptional Analyses Provide Insight into Maintaining Ion Homeostasis of Sweet Sorghum under Salt Stress.

Sweet sorghum is an important bioenergy grass and valuable forage with a strong adaptability to saline environments. However, little is known about the mechanisms of sweet sorghum coping with ion toxicity under salt stresses. Here, we first evaluated the salt tolerance of a sweet sorghum cultivar "Lvjuren" and determined its ion accumulation traits under NaCl treatments; then, we explored key genes involved in Na+, Cl-, K+ and NO3- transport using transcriptome profiling and the qRT-PCR method. The results showed that growth and photosynthesis of sweet sorghum were unaffected by 50 and 100 mM NaCl treatments, indicative of a strong salt tolerance of this species. Under NaCl treatments, sweet sorghum could efficiently exclude Na+ from shoots and accumulate Cl- in leaf sheaths to avoid their overaccumulation in leaf blades; meanwhile, it possessed a prominent ability to sustain NO3- homeostasis in leaf blades. Transcriptome profiling identified several differentially expressed genes associated with Na+, Cl-, K+ and NO3- transport in roots, leaf sheaths and leaf blades after 200 mM NaCl treatment for 6 and 48 h. Moreover, transcriptome data and qRT-PCR results indicated that HKT1;5, CLCc and NPF7.3-1 should be key genes involved in Na+ retention in roots, Cl- accumulation in leaf sheaths and maintenance of NO3- homeostasis in leaf blades, respectively. Many TFs were also identified after NaCl treatment, which should play important regulatory roles in salt tolerance of sweet sorghum. In addition, GO analysis identified candidate genes involved in maintaining membrane stability and photosynthetic capacity under salt stresses. This work lays a preliminary foundation for clarifying the molecular basis underlying the adaptation of sweet sorghum to adverse environments.

Mechanism of Yiqi Huoxue Huatan recipe in the treatment of coronary atherosclerotic disease through network pharmacology and experiments.

In recent years, with population aging and economic development, morbidity and mortality of atherosclerotic cardiovascular disease associated with atherosclerosis (AS) have gradually increased. In this study, a combination of network pharmacology and experimental verification was used to systematically explore the action mechanism of Yiqi Huoxue Huatan Recipe (YHHR) in the treatment of coronary atherosclerotic heart disease (CAD). We searched and screened the active ingredients of Coptis chinensis, Astragalus membranaceus, Salvia miltiorrhiza, and Hirudo. We also searched multiple databases for related target genes corresponding to the compounds and CAD. STRING was used to construct the protein-protein interaction (PPI) network of genes. Metascape was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common targets to analyze the main pathways, and finally, the molecular docking and main possible pathways were verified by experimental studies. Firstly, a total of 1480 predicted target points were obtained through the Swiss Target Prediction database. After screening, merging, and deleting duplicate values, a total of 768 targets were obtained. Secondly, "Coronary atherosclerotic heart disease" was searched in databases such as the OMIM, GeneCards, and TTD. 1844 disease-related targets were obtained. Among PPI network diagram of YHHR-CAD, SRC had the highest degree value, followed by AKT1, TP53, hsp90aa1 and mapk3. The KEGG pathway bubble diagram was drawn using Chiplot, the Signal pathways such as NF kappa B signaling pathway, Lipid and AS, and Apelin signaling pathway are closely related to the occurrence of CAD. The PCR and Western blot methods were used to detect the expression of NF-κB p65. When compared with that in the model group, the expression of NF-κB p65mRNA decreased in the low-concentration YHHR group, with P < .05, while the expression of NF-κB p65mRNA decreased significantly in the high-concentration YHHR group, with P < .01. On the other hand, when compared with that in the model group, the expression of NF-κB p65 decreased in the low-concentration YHHR group, but was not statistically significant, while the expression of NF-κB p65 was significant in the high-concentration YHHR group, and has statistical significance with P < .05. YHHR has been shown to resist inflammation and AS through the SRC/NF-κB signaling pathway.

Sunitinib attenuates reactive MDSCs enhancing anti-tumor immunity in HNSCC.

Enhancer of zeste homolog 2 (EZH2) is implicated in promoting HNSCC malignant progression. However, EZH2 inhibitors, when used alone, increase the number of myeloid-derived suppressor cells (MDSCs), which are responsible for enhancing tumor stemness and promoting tumor immune escape. We aimed to determine whether combining tazemetostat (an EZH2 inhibitor) and sunitinib (a MDSC inhibitor) can improve the response rate to an immune-checkpoint-blocking (ICB) therapy. We evaluated the efficacy of the above treatment strategies by bioinformatics analysis and animal experiments. EZH2 overexpression and abundant MDSCs in patients with HNSCC are associated with tumor progression. Tazemetostat treatment alone had limited inhibitory effect on HNSCC progression in the mouse models, accompanied by a surge in the number of MDSCs in the tumor microenvironment. Conversely, the combined use of tazemetostat and sunitinib reduced the number of MDSCs and regulatory T cell populations, promoting intratumoral infiltration of T cells and inhibiting of T cell exhausting, regulating of wnt/ß-catenin signaling pathway and tumor stemness, promoting the intratumoral PD-L1 expression and improved the response rate to anti-PD-1 therapy. The combined use of EZH2 and MDSC inhibitors effectively reverses HNSCC-specific immunotherapeutic resistance and is a promising strategy for overcoming resistance to ICB therapy.

The crosslink between the hyaluronic acid and drugs treated by reactive oxygen species produced in plasma based on the molecular dynamics simulation.

Hyaluronic Acid (HA)-based pre-drugs can enable targeted drug delivery to cancer cells with CD44-high expressing, thus, it is essential to design an efficient, target specific drug delivery system based on HA. Plasma, as a simple and clean tool, has been widely used in the modification and crosslinking of biological materials in recent years. In this paper, we used the Reactive Molecular Dynamic (RMD) to explore the reaction between reactive oxygen species (ROS) in plasma and HA with drugs (PTX, SN-38, and DOX), in order to examine possible drug-coupled systems. The simulation results indicated the acetylamino groups in HA could be oxidized to unsaturated acyl groups, which offers the possibility of crosslinking. Three drugs also exposed the unsaturated atoms under the impact of ROS, which can cross-link directly to HA through CO and CN bonds, forming a drug coupling system with better release. This study revealed the exposure of active sites on HA and drugs by ROS impact in plasma, allowing us to study the crosslinking mechanism between HA and drugs at molecular level deeply, and also provided a new light for establishment of HA-based targeted drug delivery system.

Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients.

Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.

Blind Deconvolution Based on Correlation Spectral Negentropy for Bearing Fault.

Blind deconvolution is a method that can effectively improve the fault characteristics of rolling bearings. However, the existing blind deconvolution methods have shortcomings in practical applications. The minimum entropy deconvolution (MED) and the optimal minimum entropy deconvolution adjusted (OMEDA) are susceptible to extreme values. Furthermore, maximum correlated kurtosis deconvolution (MCKD) and multipoint optimal minimum entropy deconvolution adjusted (MOMEDA) are required prior knowledge of faults. On the basis of the periodicity and impact of bearing fault signals, a new deconvolution algorithm, namely one based on maximum correlation spectral negentropy (CSNE), which adopts the particle swarm optimization (PSO) algorithm to solve the filter coefficients, is proposed in this paper. Verified by the simulated vibration model signal and the experimental simulation signal, the PSO-CSNE algorithm proposed in this paper overcomes the influence of harmonic signals and random pulse signals more effectively than other blind deconvolution algorithms when prior knowledge of the fault is unknown.

[Under Goals of Carbon Peaking and Carbon Neutrality: Status, Problems, and Suggestions of CCUS in China].

Under the background of global warming and climate change, carbon capture, utilization, and storage(CCUS) technology has gradually been recognized by countries around the world as one of the carbon reduction technologies with the most potential. This study described the origin, concept, positioning, and evolution process of CCUS technology in detail and compared the policies, regulations, demonstration projects, and development status of the carbon trading system of CCUS technology at home and abroad. Simultaneously, we systematically summarized the great efforts made by China to promote the development of CCUS technology since China joined the Paris Agreement in 2016, combined with the construction of ecological civilization and the objectives of "carbon peak" and "carbon neutralization." In addition, this study analyzed the existing problems of CCUS technology in China and put forward relevant development suggestions for further promoting the discovery of this technology.

Risk factor prediction of severe postoperative acute kidney injury at stage 3 in patients with acute type A aortic dissection using thromboelastography.

Objective: Perioperative blood transfusions and postoperative drainage volume not only are the commonly recognized risk factors for acute kidney injury (AKI) but also are indirect indicators of coagulopathy in patients with acute type A aortic dissection (ATAAD). However, standard laboratory tests fail to accurately reflect and assess the overall coagulopathy profile in patients with ATAAD. Thus, this study aimed to explore the association between the hemostatic system and severe postoperative AKI (stage 3) in patients with ATAAD using thromboelastography (TEG). Methods: We selected 106 consecutive patients with ATAAD who underwent emergency aortic surgery at Beijing Anzhen Hospital. All participants were categorized into the stage 3 and non-stage 3 groups. The hemostatic system was evaluated using routine laboratory tests and TEG preoperatively. We undertook univariate and multivariate stepwise logistic regression analyses to determine the potential risk factors for severe postoperative AKI (stage 3), with a special investigation on the association between hemostatic system biomarkers and severe postoperative AKI (stage 3). The receiver operating characteristic (ROC) curves were generated to assess the predictive ability of hemostatic system biomarkers for severe postoperative AKI (stage 3). Results: A total of 25 (23.6%) patients developed severe postoperative AKI (stage 3), including 21 patients (19.8%) who required continuous renal replacement therapy (RRT). Multivariate logistic regression analysis demonstrated that the preoperative fibrinogen level (OR, 2.02; 95% CI, 1.03 to 3.00; p = 0.04), platelet function (MA level) (OR, 1.23; 95% CI, 1.09 to 1.39; p = 0.001), and cardiopulmonary bypass (CPB) time (OR, 1.01; 95% CI, 1.00 to 1.02; p = 0.02) were independently associated with severe postoperative AKI (stage 3). The cutoff values of preoperative fibrinogen and platelet function (MA level) for predicting severe postoperative AKI (stage 3) were determined to be 2.56 g/L and 60.7 mm in the ROC curve [area under the curve (AUC): 0.824 and 0.829; p < 0.001]. Conclusions: The preoperative fibrinogen level and platelet function (measured by the MA level) were identified as potential predictive factors for developing severe postoperative AKI (stage 3) in patients with ATAAD. Thromboelastography could be considered a potentially valuable tool for real-time monitoring and rapid assessment of the hemostatic system to improve postoperative outcomes in patients.

Low preoperative serum fibrinogen level is associated with postoperative acute kidney injury in patients with in acute aortic dissection.

OBJECTIVE: Acute kidney injury (AKI) after cardiac surgery is associated with serious complication and high risk of mortality. The relationship between hemostatic system and the prognosis of patients with acute type A aortic dissection (ATAAD) has not been evaluated. The purpose of this study was to investigate the association between preoperative serum fibrinogen level and risk of postoperative AKI in patients with ATAAD. METHODS: A total of 172 consecutive patients undergoing urgent aortic arch surgery for ATAAD between April 2020 and December 2021 were identified from Beijing Anzhen Hospital aortic surgery database. The primary outcome was postoperative AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The univariate and multivariate logistic regression analysis were done to assess the independent predictors of risk for postoperative AKI. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive probabilities of risk factors for AKI. RESULTS: In our study, 51.2% (88/172) patients developed postoperative AKI. Multivariate logistic regression analysis identified low preoperative serum fibrinogen level (OR, 1.492; 95% CI, 1.023 to 2.476; p = 0.021) and increased body mass index (BMI) (OR, 1.153; 95% CI, 1.003 to 1.327; p = 0.046) as independent predictors of postoperative AKI in patients with ATAAD. A mixed effect analysis of variance modeling revealed that obese patients with low preoperative serum fibrinogen level had higher incidence of postoperative AKI (p = 0.04). The ROC curve indicated that low preoperative serum fibrinogen level was a significant predictor of AKI [area under the curve (AUC), 0.771; p < 0.001]. CONCLUSIONS: Low preoperative serum fibrinogen level and obesity were associated with the risk of postoperative AKI in patients with ATAAD. These data suggested that low preoperative serum fibrinogen level was preferred marker for predicting the postoperative AKI, especially in obese patients with ATAAD.