The efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis. METHODS: Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers. The quality of observational studies and randomized controlled trial (RCT) studies were evaluated by Newcastle Ottawa scale and Jadad scale, respectively. The primary outcomes included mortality, clinical cure, and microbiological cure. Secondary outcomes were recurrence and renal impairment. RESULTS: There were 30 studies were analyzed, including 12 RCT studies and 18 observational studies. Inhaled antibiotics did not significantly reduce mortality in RCT studies (odds ratio (OR) = 1.06, 95 % confidence interval (CI): 0.80-1.41). Inhaled antibiotics were associated with higher rates of clinical cure (OR = 1.47 95%CI: 0.82-2.66 in RCT studies and OR = 2.09, 95%CI: 1.36-3.21 in observational studies) and microbiological cure (OR = 7.00 in RCT studies and OR = 2.20 in observational studies). Subgroup analysis showed patients received inhaled antibiotics combined with intravenous administration and inhaled amikacin had better improvements of mortality, clinical cure and microbiological cure. Inhaled antibiotics were not associated with recurrence. The pooled OR of renal impairment were 0.65 (95%CI: 0.27-1.13; I-squared = 43.5 %, P = 0.124) and 0.63(95%CI: 0.26-1.11; I-squared = 69.0 %, P = 0.110) in RCT studies and observational studies, respectively. CONCLUSIONS: Inhaled antibiotics decreased risk of renal impairment and achieved significant improvements of clinical and microbiological cure in patients with pneumoniae.

Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells: Characterization, Differentiation, and Applications in Cartilage Tissue Engineering.

Articular cartilage defects have very limited self-repair potential, and traditional bone marrow-stimulating therapy is not effective. Cartilage tissue engineering using bone marrow mesenchymal stem cells (BMSCs) and adipose tissue-derived mesenchymal stem cells (ADSCs) is considered an attractive treatment for cartilage lesions and osteoarthritis. However, studies proved that both BMSCs and ADSCs have their own advantages and shortcomings, including their sources, isolation methods, characterizations and differentiation potential. Understanding the properties and differences between ADSCs and BMSCs is important for clinical application in cartilage regeneration. This review provides an overview of BMSCs and ADSCs based on their characterization, isolation. Then, we summarized their differentiation potential in different experimental conditions. Finally, we discuss the applications of BMSCs and ADSCs in scaffold-free and scaffold-based cartilage tissue engineering. Based on different properties of BMSCs and ADSCs, and patient's physical condition, a more suitable therapeutic strategy can be selected.

Tissue-derived scaffolds and cells for articular cartilage tissue engineering: characteristics, applications and progress.

There are many factors to consider in the field of tissue engineering. For articular cartilage repair, this includes seed cells, scaffolds and chondrotrophic hormones. This review primarily focuses on the seed cells and scaffolds. Extracellular matrix proteins provide a natural scaffold for cell attachment, proliferation and differentiation. The structure and composition of tissue-derived scaffolds and native tissue are almost identical. As such, tissue-derived scaffolds hold great promise for biomedical applications. However, autologous tissue-derived scaffolds also have many drawbacks for transplantation, as harvesting autografts is limited to available donor sites and requires secondary surgery, therefore imparting additional damage to the body. This review summarizes and analyzes various cell sources and tissue-derived scaffolds applied in orthopedic tissue engineering.

Native tissue-based strategies for meniscus repair and regeneration.

Meniscus injuries appear to be becoming increasingly common and pose a challenge for orthopedic surgeons. However, there is no curative approach for dealing with defects in the inner meniscus region due to its avascular nature. Numerous strategies have been applied to regenerate and repair meniscus defects and native tissue-based strategies have received much attention. Native tissue usually has good biocompatibility, excellent mechanical properties and a suitable microenvironment for cellular growth, adhesion, redifferentiation, extracellular matrix deposition and remodeling. Classically, native tissue-based strategies for meniscus repair and regeneration are divided into autogenous and heterogeneous tissue transplantation. Autogenous tissue transplantation is performed more widely than heterogeneous tissue transplantation because there is no immunological rejection and the success rates are higher. This review first discusses the native meniscus structure and function and then focuses on the use of the autogenous tissue for meniscus repair and regeneration. Finally, it summarizes the advantages and disadvantages of heterogeneous tissue transplantation. We hope that this review provides some suggestions for the future design of meniscus repair and regeneration strategies.

Investigations on the Performance of a Downhole Electric Heater with Different Parameters Used in Oil Shale In Situ Conversion.

In situ conversion is the most potential technology for efficient and clean development of oil shale, and a downhole electric heater is key equipment for clean, efficient, and low-carbon in situ conversion. Three electric heating rods with different diameters are used to explore their influence on heater performances. The simulation results indicate that increasing the diameter of the heating rod helps to increase the minimum and maximum velocity of shell-side air, and the maximum velocity of H110-24 is 16.34 m/s, which is 1.25 and 1.13 times those of H110-16 and H110-20, respectively. In addition, the location of the local high temperature zone coincides with the area with low air flow velocity, and increasing the diameter of the heating rod can effectively reduce the heating rod surface temperature during high-power heating. Moreover, at the same heat flux, the heat transfer coefficients of H110-24 and H110-20 are 44.82-48.49% and 87.52-95.48% higher than those of H110-16, respectively. With the same heating power, the heat transfer coefficients of heaters have the same trend, indicating that the heat transfer coefficient of the heating rod can be effectively improved by increasing the diameter of the heating rod. Finally, the newly defined comprehensive performance is used to evaluate the heaters with different heating parameters. Increasing the heating power can improve the comprehensive performance of the heater, but the most effective way is to increase the diameter of the heating rod. With the same heating power, the new comprehensive performance of H110-24 and H110-20 is 48.38-52.34% and 87.29-95.19% higher than that of H110-16, respectively, and the electric heating rod with the diameter of 20 mm has the best performance.

MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus-Related Liver Diseases.

OBJECTIVE: T-cell exhaustion in hepatitis B virus (HBV) infection, which results from upregulation of programmed cell death-1 (PD-1), leads to persistent HBV infection and related disease progression. Therefore, agents targeting PD-1 may prove beneficial in the treatment of this condition. MicroRNA-138 (miR-138) possesses an anti-tumor ability in that it targets immune checkpoints, including PD-1. However, the function and underlying mechanisms of miR-138 in patients with HBV infection remains unclear. METHODS: Specimens were collected from healthy volunteers (n = 43) and patients with chronic hepatitis B (CHB; n = 52), liver cirrhosis (LC; n = 26), and hepatocellular carcinoma (HCC; n = 31); carriers of HBV who were asymptomatic (n = 51); and patients with CHB receiving antivirus treatment (n = 11). These specimens were then used to study the expression and relationship among miR-138, PD-1, and HBV DNA viral load. To investigate the role of miR-138 in regulating PD-1 expression and determine the effect of miR-138 in regulating T-cell function, a luciferase assay and a transfection assay were each performed with primary CD3+ T cells. RESULTS: We found that PD-1 was upregulated and miR-138 was downregulated in patients with CHB, LC, and HCC. Correlations analysis revealed that PD-1 expression was positively correlated with HBV DNA viral load whereas miR-138 was negatively correlated. Luciferase assay results showed that miR-138 directly inhibited PD-1 expression by interacting with the 3'-untranslated region of PD-1. As a result of miR-138 overexpression in primary T cells, PD-1 in these T cells was downregulated and antivirus cytokines secreted by T cells were significantly upregulated. In addition, the expression levels of PD-1 and miR-138 were reversed in patients with CHB who received antivirus treatments. CONCLUSION: Results showed that miR-138 can promote T-cell responses within patients with HBV infection by inducing a PD-1 blockade. Such an effect suggests that miR-138 may serve as a new therapeutic target for the treatment of HBV infection.

An electrospun fiber reinforced scaffold promotes total meniscus regeneration in rabbit meniscectomy model.

Low vascularization in meniscus limits its regeneration ability after injury, and tissue engineering is the most promising method to achieve meniscus regeneration. In this study, we fabricated a kind of composite scaffold by decellularized meniscus extracellular matrix/polycaprolactone (DMECM/PCL) electrospinning fibers and porous DMECM, in which DMECM/PCL fibers were used as reinforcing component. The tensile modulus of the composite scaffold in longitudinal and crosswise directions were 8.5 ±â€¯1.9 and 2.3 ±â€¯0.3 MPa, respectively. Besides that, the DMECM/PCL electrospinning fibers enhanced suture resistance of the composite scaffold more than 5 times than DMECM scaffold effectively. In vitro cytocompatibility showed that the porous structure provided by DMECM component facilitated meniscus cells' proliferation. DMECM was also the main component to regulate cell behaviors, which promoted meniscus cells expressing extracellular matrix related genes such as COL I, COL II, SOX9 and AGG. Rabbits with total meniscectomy were used as animal model to evaluated the composited scaffolds performance in vivo at 3 and 6 months. Results showed that rabbits with scaffold implanting could regenerate neo-menisci in both time points. The neo-menisci had similar histology structure and biochemical content with native menisci. Although neo-menisci had inferior tensile modulus than native ones, its modulus was improved with implanting time prolonging. MRI imaging showed the signal of neo-meniscus in the body is clear, and X-ray imaging of knee joints demonstrated the implantation of scaffolds could relief joint space narrowing. Moreover, rabbits with neo-menisci had better cartilage condition in femoral condyle and tibial plateau compared than meniscectomy group. STATEMENT OF SIGNIFICANCE: We fabricated the meniscus scaffold by combining porous decellularized meniscus extracellular matrix (DMECM) and DMECM/PCL electrospinning fibers together, which used the porous structure of DMECM, and the good tensile property of electrospinning fibers. We believe single material cannot satisfy increasing needs of scaffold. Therefore, we combined not only materials but also fabrication methods together to develop scaffold to make good use of each part. DMECM in electrospinning fibers also made these two components possible to be integrated through crosslinking. Compared to existing meniscus scaffold, the composite scaffold had (1) soft structure and extrusion would not happen after implantation, (2) ability to be trimmed to suitable shape during surgery, and (3) good resistance to suture.

The application of electrospinning used in meniscus tissue engineering.

Meniscus is a fibrocartilaginous organ to redistribute stress and enhance the stability of knee joint. Meniscus injury is common and still a formidable challenge to orthopedic surgeons. Surgical techniques and allograft transplantation were primary approaches to meniscus repair, but with intrinsic limitations in clinical practice. Tissue engineering is the most promising method to repair meniscus at present. Electrospinning is a method to fabricate fibers in small scale. With different materials and parameters, electrospinning materials could have different mechanical properties, porosity, and orientation, which could mimic architectural features and mechanical properties of native meniscus. Therefore, electrospinning materials could be used in meniscus regeneration and curing. This review gave a brief introduction of meniscus structure, injury, treatment and the application of electrospinning fibers in meniscus tissue engineering and curing. Besides that, we summarized materials commonly used in electrospinning to fabricate meniscus scaffolds, and discussed the form of electrospinning fibers used such as scaffold, substitute and patch. Finally, the function of electrospinning fibers, for example, carrying drugs, providing mechanical properties were described. The potential applications of electrospinning fibers in meniscus therapy were proposed.

Applications of stem cell-derived exosomes in tissue engineering and neurological diseases.

Exosomes are extracellular vesicles with diameters of 30-100 nm that are key for intercellular communication. Almost all types of cell, including dendritic cells, T cells, mast cells, epithelial cells, neuronal cells, adipocytes, mesenchymal stem cells, and platelets, can release exosomes. Exosomes are present in human body fluids, such as urine, amniotic fluid, malignant ascites, synovial fluid, breast milk, cerebrospinal fluid, semen, saliva, and blood. Exosomes have biological functions in immune response, antigen presentation, intercellular communication, and RNA and protein transfer. This review provides a brief overview of the origin, morphological characteristics, enrichment and identification methods, biological functions, and applications in tissue engineering and neurological diseases of exosomes.

Biomechanical Stimulus Based Strategies for Meniscus Tissue Engineering and Regeneration.

Meniscus injuries are very common in the knee joint. Treating a damaged meniscus continues to be a scientific challenge in sport medicine because of its poor self-healing potential and few clinical therapeutic options. Tissue engineering strategies are very promising solutions for repairing and regenerating a damaged meniscus. Meniscus is exposed to a complex biomechanical microenvironment, and it plays a crucial role in meniscal development, growth, and repairing. Over the past decades, increasing attention has been focused on the use of biomechanical stimulus to enhance biomechanical properties of the engineered meniscus. Further understanding the influence of mechanical stimulation on cell proliferation and differentiation, metabolism, relevant gene expression, and pro/anti-inflammatory responses may be beneficial to enhance meniscal repair and regeneration. On the one hand, this review describes some basic information about meniscus; on the other hand, we sum up the various biomechanical stimulus based strategies applied in meniscus tissue engineering and how these factors affect meniscal regeneration. We hope this review will provide researchers with inspiration on tissue engineering strategies for meniscus regeneration in the future.

Biochemical Stimulus-Based Strategies for Meniscus Tissue Engineering and Regeneration.

Meniscus injuries are very common and still pose a challenge for the orthopedic surgeon. Meniscus injuries in the inner two-thirds of the meniscus remain incurable. Tissue-engineered meniscus strategies seem to offer a new approach for treating meniscus injuries with a combination of seed cells, scaffolds, and biochemical or biomechanical stimulation. Cell- or scaffold-based strategies play a pivotal role in meniscus regeneration. Similarly, biochemical and biomechanical stimulation are also important. Seed cells and scaffolds can be used to construct a tissue-engineered tissue; however, stimulation to enhance tissue maturation and remodeling is still needed. Such stimulation can be biomechanical or biochemical, but this review focuses only on biochemical stimulation. Growth factors (GFs) are one of the most important forms of biochemical stimulation. Frequently used GFs always play a critical role in normal limb development and growth. Further understanding of the functional mechanism of GFs will help scientists to design the best therapy strategies. In this review, we summarize some of the most important GFs in tissue-engineered menisci, as well as other types of biological stimulation.