Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets.

The immune response holds a pivotal role in cardiovascular disease development. As multifunctional cells of the innate immune system, macrophages play an essential role in initial inflammatory response that occurs following cardiovascular injury, thereby inducing subsequent damage while also facilitating recovery. Meanwhile, the diverse phenotypes and phenotypic alterations of macrophages strongly associate with distinct types and severity of cardiovascular diseases, including coronary heart disease, valvular disease, myocarditis, cardiomyopathy, heart failure, atherosclerosis and aneurysm, which underscores the importance of investigating macrophage regulatory mechanisms within the context of specific diseases. Besides, recent strides in single-cell sequencing technologies have revealed macrophage heterogeneity, cell-cell interactions, and downstream mechanisms of therapeutic targets at a higher resolution, which brings new perspectives into macrophage-mediated mechanisms and potential therapeutic targets in cardiovascular diseases. Remarkably, myocardial fibrosis, a prevalent characteristic in most cardiac diseases, remains a formidable clinical challenge, necessitating a profound investigation into the impact of macrophages on myocardial fibrosis within the context of cardiac diseases. In this review, we systematically summarize the diverse phenotypic and functional plasticity of macrophages in regulatory mechanisms of cardiovascular diseases and unprecedented insights introduced by single-cell sequencing technologies, with a focus on different causes and characteristics of diseases, especially the relationship between inflammation and fibrosis in cardiac diseases (myocardial infarction, pressure overload, myocarditis, dilated cardiomyopathy, diabetic cardiomyopathy and cardiac aging) and the relationship between inflammation and vascular injury in vascular diseases (atherosclerosis and aneurysm). Finally, we also highlight the preclinical/clinical macrophage targeting strategies and translational implications.

Experimental Study on the Backflow Mechanism of Proppants in Induced Fractures and Fiber Sand Control Under the Condition of Large-Scale and Fully Measurable Flow Field.

The proppant backflow in the process of flowback has a great significant effect on gas field development. Therefore, the study of proppant backflow is of great significance for the development and production of gas wells. At present, the physical simulation methods for proppant backflow mainly include the tube perforation model, the slot model, an API standard flow tester, and a large-scale flowback apparatus. The current experimental methods are unable to observe the backflow of proppants during the process of the flowback test. In addition, the only characterization parameter for proppant backflow is the liquid flow rate corresponding to the sand discharge in the diversion chamber called critical velocity, which is too simple and single to accurately characterize the movement state of proppants during the flowback process. In this paper, a physical simulation method of proppant backflow in fractures based on the measurement of flow field was proposed. It can realize the observation and fine description of the proppant backflow state and movement rule. In addition, the process of proppant backflow can be quantitatively described by a multidimensional characterization parameter. The research shows that (1) the proppant backflow is closely related to the shape of the sand bank formed during the proppant placement and the irregular voids formed; (2) the fiber increases the strength of the proppant pack significantly; (3) the critical velocity with fiber increased by 2.25 times compared with the critical velocity without fiber, the optimum fiber concentration was 0.8%, and the fiber length was 12 mm; (4) the full fiber injection was selected as the best injection mode by the experiment; and (5) the whole process of flowback can be divided into two stages. In the strong fluid shear stage, the effect of fiber sand control is more significant. However, when the flowback enters the stage of slow erosion, the difference in the sand control effect under different parameters is no longer significant.

Experimental Study on a Liquid-Solid Phase-Change Autogenous Proppant Fracturing Fluid System.

In this paper, a liquid-solid phase-change autogenous proppant fracturing fluid system (LSPCAP) was proposed to solve the problems that was caused by "sand-carrying" in conventional fracturing technology in oil and gas fields. The characteristic of the new fluid system is that no solid particles will be injected in the whole process of fracturing construction except liquids. The fluid itself will transform into solid particles under the formation temperature to resist the closure stress in the fractures. There are two kinds of liquids that make up the new fracturing fluid system. One of the liquids is called phase-change liquid (PCL) which occurs in the liquid-solid phase change under the formation temperature to form solid particles. Another is called nonphase-change liquid (NPCL) which controls the dispersity and size of PCL in the two-phase fluid system. Based on the molecular interaction theory and organic chemistry, bisphenol-A epoxy resin was selected as the building unit of the PCL, and the NPCL consisted of deionized water + nonionic surfactant. The test results indicated that the new fracturing fluid shows the properties of non-Newtonian fluid and has no wall-building property. The new fluid system has good compatibility with the formation fluid, conventional fracturing fluid, and hydrochloric acid. Through the filtration test, the filtration coefficients of PCL, NPCL, and mixture are found to be 1.56 × 10-4 m/s1/2, 2.66 × 10-4 m/s1/2, and 1.7 × 10-4 m/s1/2, respectively, and the damage rate of mixture and NPCL is 18 and 17.7%. The friction test results show that the resistance reduction rate reaches 69% when the volume ratio of PCL and NPCL is 1:10. The shear rate and time only affect the size of the autogenous solid particles, and the sorting coefficient (S) of the particles is 1.04-1.73, indicating good sorting. Crushing resistance and conductivity test results show that the crush rate of autogenous solid particles is 3.56-8.42%. The conductivity of the autogenous solid particles is better than those of quartz sand and ceramsite under a pressure of 10-30 MPa.

Advances in the Detection, Mechanism and Therapy of Chronic Kidney Disease.

Chronic Kidney Disease (CKD) is characterized by the gradual loss of renal mass and functions. It has become a global health problem, with hundreds of millions of people being affected. Both its incidence and prevalence are increasing over time. More than $20,000 are spent on each patient per year. The economic burden on the patients, as well as the society, is heavy and their life quality worsen over time. However, there are still limited effective therapeutic strategies for CKD. Patients mainly rely on dialysis and renal transplantation, which cannot prevent all the complications of CKD. Great efforts are needed in understanding the nature of CKD progression as well as developing effective therapeutic methods, including pharmacological agents. This paper reviews three aspects in the research of CKD that may show great interests to those who devote to bioanalysis, biomedicine and drug development, including important endogenous biomarkers quantification, mechanisms underlying CKD progression and current status of CKD therapy.

Sodium Selenite Improves The Therapeutic Effect Of BMSCs Via Promoting The Proliferation And Differentiation, Thereby Promoting The Hematopoietic Factors.

PURPOSE: Sodium selenite (Na2SeO3) has been known to restore the antioxidant capacity of bone marrow mesenchymal stem cells (BMSCs), reduce the production of reactive oxygen species (ROS) in the cells, and promote cell proliferation and inhibit cell apoptosis. However, it is still not clear whether selenium can mediate the differentiation and inhibit the induced hemagglutination of BMSCs. In this study, we attempted to explore the effect of Na2SeO3 on these aspects of BMSCs. METHODS: We evaluated the fate of the MSCs isolated from the bone marrow of mice by studying their differentiation and proliferation after treatment with Na2SeO3. We also simultaneously evaluated the coagulation reaction induced by Na2SeO3-treated BMSCs in vitro. RESULTS: While the mice-derived BMSCs expressed CD44, CD73, CD90, and CD105, they did not express CD45. The morphology of the derived cells was homogeneously elongated. These results showed that the isolated cells are indeed BMSCs. We found that 0.1 µM and 1 µM of Na2SeO3 promoted the proliferation and apoptosis of BMSCs, respectively. This showed that Na2SeO3 can be toxic and exert certain side effects on the BMSCs. The results of the osteogenic and adipogenic assay showed that 0.1 µM Na2SeO3 could significantly promote the osteogenic and adipogenic differentiation of BMSCs by upregulating the lipid factors (LPL and PPRAG) and osteogenic factors, RUNX2, COL1, and BGP, in a concentration-dependent manner. Coagulation experiments in animals (mice and rats) revealed that Na2SeO3 can reduce the coagulation time of BMSCs in a concentration-dependent manner, which is related to the high expression of hematopoietic factors (SDF-1α, GM-CSF, IL-7, IL-8, IL-11, and SCF). CONCLUSION: Na2SeO3 promotes the proliferation and differentiation as well as reduces the coagulation time of BMSCs, and this effect might enhance the therapeutic effect of BMSCs.

Multi-tract percutaneous nephrolithotomy combined with EMS lithotripsy for bilateral complex renal stones: our experience.

BACKGROUND: The treatment of bilateral complex renal stones is a tough challenge for urologists. This study aimed to evaluate the efficiency and safety of bilateral ultrasonography-guided multi-tract percutaneous nephrolithotomy (PCNL) combined with EMS lithotripsy for the treatment of such cases. METHODS: Twenty-seven patients suffering from bilateral complex renal calculi underwent t bilateral multi-tract PCNL. The PCNL began with the establishment of percutaneous nephrostomy access, which was achieved under ultrasound guidance followed by stone fragment and removal by EMS lithotripsy. The same processes were then performed on the ipsilateral and contralateral renal units until the operation terminated. Sheaths left in situ to provide the tracts for the two-stage and the three-stage PCNL procedures. Peri- and postoperative clinical data were collected and analysed. RESULTS: Renal stones of both sides were completely cleared within three PCNL sessions in 24 cases. Among them, four, thirteen, and seven cases underwent single, second-stage and third-stage procedures, respectively. The total stone-free rate was 88.9%. Three patients failed to receive complete stone clearance. Mean operation time was 78.7 (26-124) min, the mean estimated blood loss was 97.3 (30-250) ml, and the mean length of hospital stay was 18 (10-31) days. No patient required blood transfusion and postoperative fever occurred in 6 cases. Within the follow-up period, stone recurrence occurred in 6 patients. CONCLUSIONS: Ultrasonography-guided multi-tract PCNL using EMS is an efficient method for the treatment of complex renal calculi. According to our experience, it is safe to make multiple tracts on both sides simultaneously.