Combined aerobic and resistance exercise in maintenance hemodialysis patients: A meta-analysis.

Exercise brings many benefits to patients undergoing maintenance hemodialysis (MHD), but the effect of combined aerobic and resistance exercise remains unclear. English and Chinese databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, VIP, Wan Fang, and CBM) were searched from inception to January 2023 to retrieve qualified randomized controlled trials. The literature selection, data extraction, and risk of bias assessment of included studies were conducted independently by two reviewers. Meta-analysis was performed using RevMan 5.3 software. A total of 23 studies with 1214 participants were included, and 17 of the interventions were conducted during dialysis. Results showed that combined aerobic and resistance exercise (CARE) improved the peak oxygen uptake, six-minute walking test, 60 s sit-to-stand test (STS), 30 s STS, dialysis adequacy, five (out of eight) domains and physical component summary of health-related quality of life (HRQOL) measured by the Medical Outcomes Study Short Form-36, blood pressure, and hemoglobin for MHD patients compared with usual care. No significant changes were found in the mental component summary of HRQOL, C-reactive protein, creatinine, potassium, sodium, calcium, and phosphate. Subgroup analysis showed that intradialytic CARE ameliorated more outcomes, except for handgrip strength and hemoglobin, than non-intradialytic ones. CARE is an effective way to improve physical function, aerobic capacity, dialysis adequacy, and HRQOL for MHD patients. Strategies should be implemented by clinicians and policymakers to motivate patients to do more exercise. Well-designed clinical trials are warranted to explore the effectiveness of non-intradialytic CARE.

[A clinical study of invasive fungal disease in children without underlying diseases].

OBJECTIVE: To investigate the clinical features of invasive fungal disease (IFD) in children without underlying diseases. METHODS: The clinical data of 49 children without underlying diseases who were diagnosed with IFD were retrospectively studied. RESULTS: Fungal pathogens were detected in 37 (76%) out of 49 patients, including Cryptococcus neoformans (17 children, 46%), Candida albicans (10 children, 27%), Aspergillus (3 children, 8%), and Candida parapsilosis (3 children, 8%). Fungal pneumonia (17 children, 46%) was the most commonly seen disease, with Candida albicans as the major pathogen (9 children, 53%). The 49 children had at least one high-risk factor for infection, including the use of antibiotics, a long length of hospital stay, and invasive procedures. Of all the children, 82% did not respond well to antibiotic treatment or experienced recurrent pyrexia. Among the 24 children who underwent G tests, 17 (71%) showed positive results. All the children were given antifungal therapy, and among these children, 37 (75%)were cured, 3 (6%) were still in the treatment, 5 (10%) died, and 4 (8%) were lost to follow-up. CONCLUSIONS: In IFD children without underlying diseases, Cryptococcus neoformans and Candida are the main pathogens, and lung infection is the most common disease. Long-term use of high-dose antibiotics may be an important risk factor for fungal infection. The IFD children without underlying diseases are sensitive to antifungal drugs and have a satisfactory prognosis.

[A young boy with elevated aminotransferases in physical examination--Two novel missense mutations associated with Wilson's disease were found].

A 3-year-old boy had abnormal liver function, which was found in physical examination, for 5 months before admission. He had no symptoms such as anorexia, poor appetite, and jaundice, had normal growth and development, and showed no hepatosplenomegaly. Laboratory examination revealed significantly reduced ceruloplasmin (35 mg/L), as well as negative hepatotropic virus, cytomegalovirus, and Epstein-Barr virus. There were normal muscle enzymes, blood glucose, and blood ammonia and negative liver-specific autoantibodies. The boy had negative K-F ring and normal 24-hour urine copper (0.56 µmol/L). The ATP7B gene testing for the boy, his sister, and their parents detected two novel missense mutations in the boy and his sister, i.e., compound heterozygous mutations in exon 7 (c.2075T>C, p.L692P) and exon 13 (c.3044T>C, p.L1015P), which were inherited from their father and mother, respectively. Wilson's disease was confirmed by genetic diagnosis in the boy and his sister. The boy and his sister were given a low-copper diet. The boy was administered with penicillamine for decoppering and zinc supplement against copper uptake. His sister received zinc supplement alone because no clinical symptoms were observed. The boy showed normal liver function in the reexamination after 3 months of treatment.

Microenvironment-responsive release of Mg2+ from tannic acid decorated and multilevel crosslinked hydrogels accelerates infected wound healing.

The management of chronic infected wounds poses significant challenges due to frequent bacterial infections, high concentrations of reactive oxygen species, abnormal immune regulation, and impaired angiogenesis. This study introduces a novel, microenvironment-responsive, dual dynamic, and covalently bonded hydrogel, termed OHA-P-TA/G/Mg2+. It is derived from the reaction of tannic acid (TA) with phenylboronic acids (PBA), which are grafted onto oxidized hyaluronic acid (OHA-P-TA), combined with GelMA (G) via a Schiff base and chemical bonds, along with the incorporation of Mg2+. This hydrogel exhibits pH and ROS dual-responsiveness, demonstrating effective antibacterial capacity, antioxidant ability, and the anti-inflammatory ability under distinct acidic and oxidative microenvironments. Furthermore, the release of Mg2+ from the TA-Mg2+ network (TA@Mg2+) promotes the transformation of pro-inflammatory M1 phenotype macrophages to anti-inflammatory M2 phenotype, showing a microenvironment-responsive response. Finally, in vivo results indicate that the OHA-P-TA/G/Mg2+ hydrogel enhances epithelial regeneration, collagen deposition, and neovascularization, showing great potential as an effective dressing for infected wound repair.

An injectable cartilage-coating composite with long-term protection, effective lubrication and chondrocyte nourishment for osteoarthritis treatment.

The osteoarthritic (OA) environment within articular cartilage poses significant challenges, resulting in chondrocyte dysfunction and cartilage matrix degradation. While intra-articular injections of anti-inflammatory drugs, biomaterials, or bioactive agents have demonstrated some effectiveness, they primarily provide temporary relief from OA pain without arresting OA progression. This study presents an injectable cartilage-coating composite, comprising hyaluronic acid and decellularized cartilage matrix integrated with specific linker polymers. It enhances the material retention, protection, and lubrication on the cartilage surface, thereby providing an effective physical barrier against inflammatory factors and reducing the friction and shear force associated with OA joint movement. Moreover, the composite gradually releases nutrients, nourishing OA chondrocytes, aiding in the recovery of cellular function, promoting cartilage-specific matrix production, and mitigating OA progression in a rat model. Overall, this injectable cartilage-coating composite offers promising potential as an effective cell-free treatment for OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) in the articular cartilage leads to chondrocyte dysfunction and cartilage matrix degradation. This study introduces an intra-articular injectable composite material (HDC), composed of decellularized cartilage matrix (dECMs), hyaluronan (HA), and specially designed linker polymers to provide an effective cell-free OA treatment. The linker polymers bind HA and dECMs to form an integrated HDC structure with an enhanced degradation rate, potentially reducing the need for frequent injections and associated trauma. They also enable HDC to specifically coat the cartilage surface, forming a protective and lubricating layer that enhances long-term retention, acts as a barrier against inflammatory factors, and reduces joint movement friction. Furthermore, HDC nourishes OA chondrocytes through gradual nutrient release, aiding cellular function recovery, promoting cartilage-specific matrix production, and mitigating OA progression.

Injectable Microgels with Hybrid Exosomes of Chondrocyte-Targeted FGF18 Gene-Editing and Self-Renewable Lubrication for Osteoarthritis Therapy.

Abnormal silencing of fibroblast growth factor (FGF) signaling significantly contributes to joint dysplasia and osteoarthritis (OA); However, the clinical translation of FGF18-based protein drugs is hindered by their short half-life, low delivery efficiency and the need for repeated articular injections. This study proposes a CRISPR/Cas9-based approach to effectively activate the FGF18 gene of OA chondrocytes at the genome level in vivo, using chondrocyte-affinity peptide (CAP) incorporated hybrid exosomes (CAP/FGF18-hyEXO) loaded with an FGF18-targeted gene-editing tool. Furthermore, CAP/FGF18-hyEXO are encapsulated in methacrylic anhydride-modified hyaluronic (HAMA) hydrogel microspheres via microfluidics and photopolymerization to create an injectable microgel system (CAP/FGF18-hyEXO@HMs) with self-renewable hydration layers to provide persistent lubrication in response to frictional wear. Together, the injectable CAP/FGF18-hyEXO@HMs, combined with in vivo FGF18 gene editing and continuous lubrication, have demonstrated their capacity to synergistically promote cartilage regeneration, decrease inflammation, and prevent ECM degradation both in vitro and in vivo, holding great potential for clinical translation.

Optimization of exosome-based cell-free strategies to enhance endogenous cell functions in tissue regeneration.

Exosomes, nanoscale extracellular vesicles, play a crucial role in intercellular communication, owing to their biologically active cargoes such as RNAs and proteins. In recent years, they have emerged as a promising tool in the field of tissue regeneration, with the potential to initiate a new trend in cell-free therapy. However, it's worth noting that not all types of exosomes derived from cells are appropriate for tissue repair. Thus, selecting suitable cell sources is critical to ensure their efficacy in specific tissue regeneration processes. Current therapeutic applications of exosomes also encounter several limitations, including low-specific content for targeted diseases, non-tissue-specific targeting, and short retention time due to rapid clearance in vivo. Consequently, this review paper focuses on exosomes from diverse cell sources with functions specific to tissue regeneration. It also highlights the latest engineering strategies developed to overcome the functional limitations of natural exosomes. These strategies encompass the loading of specific therapeutic contents into exosomes, the endowment of tissue-specific targeting capability on the exosome surface, and the incorporation of biomaterials to extend the in vivo retention time of exosomes in a controlled-release manner. Collectively, these innovative approaches aim to synergistically enhance the therapeutic effects of natural exosomes, optimizing exosome-based cell-free strategies to boost endogenous cell functions in tissue regeneration. STATEMENT OF SIGNIFICANCE: Exosome-based cell-free therapy has recently emerged as a promising tool for tissue regeneration. This review highlights the characteristics and functions of exosomes from different sources that can facilitate tissue repair and their contributions to the regeneration process. To address the functional limitations of natural exosomes in therapeutic applications, this review provides an in-depth understanding of the latest engineering strategies. These strategies include optimizing exosomal contents, endowing tissue-specific targeting capability on the exosome surface, and incorporating biomaterials to extend the in vivo retention time of exosomes in a controlled-release manner. This review aims to explore and discuss innovative approaches that can synergistically improve endogenous cell functions in advanced exosome-based cell-free therapies for a broad range of tissue regeneration.

Structure-Based Multilevel Descriptors for High-throughput Screening of Elastomers.

To discover new materials, high-throughput screening (HTS) with machine learning (ML) requires universally available descriptors that can accurately predict the desired properties. For elastomers, experimental and simulation data in current descriptors may not be available for all candidates of interest, hindering elastomer discovery through HTS. To address this challenge, we introduce structure-based multilevel (SM) descriptors of elastomers derived solely from molecular structure that is universally available. Our SM descriptors are hierarchically organized to capture both local soft and hard segment structures as well as the global structures of elastomers. With the SM-Morgan Fingerprint (SM-MF) descriptor, one of our SM descriptors, a machine learning model accurately predicts elastomer toughness with a remarkable accuracy of 0.91. Furthermore, an HTS pipeline is established to swiftly screen elastomers with targeted toughness. We also demonstrate the generality and applicability of SM descriptors by using them to construct HTS pipelines for screening elastomers with a targeted critical strain or Young's modulus. The user-friendliness and low computational cost of SM descriptors make them a promising tool to significantly enhance HTS in the search for novel materials.

Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes.

As chondrocytes from osteoarthritic cartilage usually exhibit aging and senescent characteristics, targeting aging chondrocytes could be a potential therapeutic strategy. In this study, exosomes derived from umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combined with the chondrocyte-targeting capacity and controlled-release system were proposed for osteoarthritis (OA) treatment via rejuvenating aging chondrocytes. The essential functional miRNAs within UCMSC-EXOs were investigated, with the p53 signaling pathway identified as the key factor. To improve the therapeutic efficiency and retention time of UCMSC-EXOs in vivo, the exosomes (EXOs) were engineered on membranes with a designed chondrocyte-targeting polymers, and encapsulated within thiolated hyaluronic acid microgels to form a "two-phase" releasing system, which synergistically facilitated the repair of OA cartilage in a rat model. Together, this study highlighted the rejuvenating effects of UCMSC-EXOs on OA chondrocytes and the potential to combine with chondrocyte-targeting and sustained-release strategies toward a future cell-free OA treatment.

[Factors influencing short-term prognosis of tuberculous meningitis in children].

OBJECTIVE: To study the factors influencing short-term prognosis of tuberculous meningitis (TBM) in children. METHODS: The clinical data of 137 hospitalized children with TBM between January 2007 and February 2011 were retrospectively reviewed. A total of 30 potential factors influencing short-term prognosis of TBM were evaluated by univariate analysis and multivariate logistic regression analysis. RESULTS: Clinical staging showed that of the 137 children 21 cases (15.3%) were in the early stage, 67 cases (48.9%) in the medium stage and 49 cases (35.8%) in the late stage of TBM. The univariate analysis revealed 8 factors associated with a poor short-term prognosis: clinical stage of TBM (late), coma, positive Babinski signs, cranial nerve involvements, paralysis, seizures, obvious abnormalities in brain computed tomography (CT) or magnetic resonance imaging (MRI) and elevated protein concentrations in cerebrospinal fluid (CSF). Factors associated with a favourable short-term prognosis for TBM included glucocorticoid steroids therapy, positive reaction of PPD skin test and an increased length of stay in hospital. Multivariate logistic analysis revealed two independent risk factors for a poor short-term prognosis: clinical stage of TBM (late) (OR: 11.168, 95%CI: 3.521-35.426) and positive signs of meningeal irritation (OR: 4.275, 95%CI: 1.043-17.521). An increased length of stay in hospital was shown as a favorable factor (OR: 0.893, 95%CI: 0.825-0.968). CONCLUSIONS: Late-stage TBM and positive signs of meningeal irritation suggest a poor prognosis, while an appropriately longer length of stay in hospital may contribute to a favorable short-term prognosis for children with TBM.

[Nasal carriage of community-acquired methicillin-resistant Staphylococcus aureus in healthy children from Chengdu].

OBJECTIVE: To evaluate the prevalence of nasal carriage of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in healthy children from Chengdu. METHODS: Strains of Staphylococcus aureus were isolated from nasal swabs of healthy children from five kindergartens in Chengdu from September, 2005 to December, 2005 and questionnaires were obtained. Antibiotic susceptibility test was performed with agar disk diffusion and Bauer-Kirby on Mueller-Hinton medium method to determine CA-MRSA. mecA and PVL genes were detected with PCR in all of the CA-MRSA isolates. RESULTS: A total of 801 children were enrolled. Overall 147 children (18.4%) were carried with Staphylococcus aureus and 9 (1.1%) were carried with CA-MRSA. All CA-MRSA isolates were positive for mecA gene, and 5 CA-MRSA isolates were positive for PVL gene. Of the 9 CA-MRSA isolates, 6 were multiresistant. CONCLUSIONS: CA-MRSA nasal colonization is present among Chengdu healthy children. The CA-MRSA isolates are multiresistant and parts of CA-MRSA isolates carry PVL gene. The nasal carriage of CA-MRSA in healthy children should be a concerned issue.

Controlled droplet transport to target on a high adhesion surface with multi-gradients.

We introduce multi-gradients including Laplace pressure gradient, wettable gradient and wettable different gradient on a high adhesion surface via special wedge-pattern and improved anodic oxidation method. As a result of the cooperative effect mentioned above, controlled directional motion of a droplet on a high adhesion surface is realized, even when the surface is turned upside down. The droplet motion can be predicted and the movement distances can be controlled by simply adjusting the wedge angle and droplet volume. More interestingly, when Laplace pressure gradient is introduced on a V-shaped wettable gradient surface, two droplets can move toward one another as designed.

Radial wettable gradient of hot surface to control droplets movement in directions.

A radial wettable gradient was fabricated on the surface of graphite plate by a simple one-step anodic oxidation process. It was found that the direction and value of the wettable gradient could be easily controlled by adjusting current and oxidation time gradient. With the increase of surface temperature, droplets on surface not only exhibited the transition of boiling mode, but also showed the controlled radial spreading, evaporation and movement behaviors. These phenomena could be attributed to the cooperation of wettability force, hysteresis force and vapor pressure (Leidenfrost effect). Especially, the controlled radial convergence or divergence of droplets with high velocity were realized on the surfaces with either inside or outside radial gradient, which would have crucial applications in the design of microfluidic devices and the exploration of the biotechnology.

Primary cavitating tuberculosis in a 2-month-old infant.

Cavitation in primary pulmonary tuberculosis is rare, particularly in infants. We report a case of a 2-month-old infant with primary cavitating tuberculosis. Computed tomography first showed consolidation of the left upper lobe, and results of a course of antimicrobial therapy demonstrated a cystic lesion. The cyst was demonstrated to be a tuberculous cavity by postoperative histopathologic examination.