Decellularized laser micro-patterned osteochondral implants exhibit zonal recellularization and self-fixing for osteochondral regeneration in a goat model.

Background: Osteochondral regeneration has long been recognized as a complex and challenging project in the field of tissue engineering. In particular, reconstructing the osteochondral interface is crucial for determining the effectiveness of the repair. Although several artificial layered or gradient scaffolds have been developed recently to simulate the natural interface, the functions of this unique structure have still not been fully replicated. In this paper, we utilized laser micro-patterning technology (LMPT) to modify the natural osteochondral "plugs" for use as grafts and aimed to directly apply the functional interface unit to repair osteochondral defects in a goat model. Methods: For in vitro evaluations, the optimal combination of LMPT parameters was confirmed through mechanical testing, finite element analysis, and comparing decellularization efficiency. The structural and biological properties of the laser micro-patterned osteochondral implants (LMP-OI) were verified by measuring the permeability of the interface and assessing the recellularization processes. In the goat model for osteochondral regeneration, a conical frustum-shaped defect was specifically created in the weight-bearing area of femoral condyles using a customized trephine with a variable diameter. This unreported defect shape enabled the implant to properly self-fix as expected. Results: The micro-patterning with the suitable pore density and morphology increased the permeability of the LMP-OIs, accelerated decellularization, maintained mechanical stability, and provided two relative independent microenvironments for subsequent recellularization. The LMP-OIs with goat's autologous bone marrow stromal cells in the cartilage layer have securely integrated into the osteochondral defects. At 6 and 12 months after implantation, both imaging and histological assessments showed a significant improvement in the healing of the cartilage and subchondral bone. Conclusion: With the natural interface unit and zonal recellularization, the LMP-OI is an ideal scaffold to repair osteochondral defects especially in large animals. The translational potential of this article: These findings suggest that such a modified xenogeneic osteochondral implant could potentially be explored in clinical translation for treatment of osteochondral injuries. Furthermore, trimming a conical frustum shape to the defect region, especially for large-sized defects, may be an effective way to achieve self-fixing for the implant.

Injectable and in situ foaming shape-adaptive porous Bio-based polyurethane scaffold used for cartilage regeneration.

Irregular articular cartilage injury is a common type of joint trauma, often resulting from intense impacts and other factors that lead to irregularly shaped wounds, the limited regenerative capacity of cartilage and the mismatched shape of the scaffods have contributed to unsatisfactory therapeutic outcomes. While injectable materials are a traditional solution to adapt to irregular cartilage defects, they have limitations, and injectable materials often lack the porous microstructures favorable for the rapid proliferation of cartilage cells. In this study, an injectable porous polyurethane scaffold named PU-BDO-Gelatin-Foam (PUBGF) was prepared. After injection into cartilage defects, PUBGF forms in situ at the site of the defect and exhibits a dynamic microstructure during the initial two weeks. This dynamic microstructure endows the scaffold with the ability to retain substances within its interior, thereby enhancing its capacity to promote chondrogenesis. Furthermore, the chondral repair efficacy of PUBGF was validated by directly injecting it into rat articular cartilage injury sites. The injectable PUBGF scaffold demonstrates a superior potential for promoting the repair of cartilage defects when compared to traditional porous polyurethane scaffolds. The substance retention ability of this injectable porous scaffold makes it a promising option for clinical applications.

Leaf diffusional capacity largely contributes to the reduced photosynthesis in rice plants under magnesium deficiency.

Numerous studies have clarified the impacts of magnesium (Mg) on leaf photosynthesis from the perspectives of protein synthesis, enzymes activation and carbohydrate partitioning. However, it still remains largely unknown how stomatal and mesophyll conductances (gs and gm, respectively) are regulated by Mg. In the present study, leaf gas exchanges, leaf hydraulic parameters, leaf structural traits and cell wall composition were examined in rice plants grown under high and low Mg treatments to elucidate the impacts of Mg on gs and gm. Our results showed that reduction of leaf photosynthesis under Mg deficiency was mainly caused by the decreased gm, followed by reduced leaf biochemical capacity and gs, and leaf outside-xylem hydraulic conductance (Kox) was the major factor restricting gs under Mg deficiency. Moreover, increased leaf hemicellulose, lignin and pectin contents and decreased cell wall effective porosity were observed in low Mg plants relative to high Mg plants. These results suggest that Kox and cell wall composition play important roles in regulating gs and gm, respectively, in rice plants under Mg shortages.

Nomogram-based risk assessment model for left ventricular hypertrophy in patients with essential hypertension: Incorporating clinical characteristics and biomarkers.

Left ventricular hypertrophy (LVH) is a hypertensive heart disease that significantly escalates the risk of clinical cardiovascular events. Its etiology potentially incorporates various clinical attributes such as gender, age, and renal function. From mechanistic perspective, the remodeling process of LVH can trigger increment in certain biomarkers, notably sST2 and NT-proBNP. This multicenter, retrospective study aimed to construct an LVH risk assessment model and identify the risk factors. A total of 417 patients with essential hypertension (EH), including 214 males and 203 females aged 31-80 years, were enrolled in this study; of these, 161 (38.6%) were diagnosed with LVH. Based on variables demonstrating significant disparities between the LVH and Non-LVH groups, three multivariate stepwise logistic regression models were constructed for risk assessment: the "Clinical characteristics" model, the "Biomarkers" model (each based on their respective variables), and the "Clinical characteristics + Biomarkers" model, which amalgamated both sets of variables. The results revealed that the "Clinical characteristics + Biomarkers" model surpassed the baseline models in performance (AUC values of the "Clinical characteristics + Biomarkers" model, the "Biomarkers" model, and the "Clinical characteristics" model were .83, .75, and .74, respectively; P < .0001 for both comparisons). The optimized model suggested that being female (OR: 4.26, P <.001), being overweight (OR: 1.88, p = .02) or obese (OR: 2.36, p = .02), duration of hypertension (OR: 1.04, P = .04), grade III hypertension (OR: 2.12, P < .001), and sST2 (log-transformed, OR: 1.14, P < .001) were risk factors, while eGFR acted as a protective factor (OR: .98, P = .01). These findings suggest that the integration of clinical characteristics and biomarkers can enhance the performance of LVH risk assessment.

Research prospects for kidney xenotransplantation: a bibliometric analysis.

BACKGROUND: Xenograft kidney transplantation has been receiving increasing attention. The purpose of this study is to use bibliometric analysis to identify papers in this research field and explore their current status and development trends. METHODS: Using the data in the Web of Science core database from Clarivate Analytics as the object of study, we used 'TS = Kidney OR Renal AND xenotransplantation' as the search term to find all literature from 1980 to 2 November 2022. RESULTS: In total, 1005 articles were included. The United States has the highest number of publications and has made significant contributions in this field. Harvard University was at the forefront of this study. Professor Cooper has published 114 articles in this field. Xenotransplantation has the largest number of relevant articles. Transplantation was the most cited journal. High-frequency keywords illustrated the current state of development and future trends in xenotransplantation. The use of transgenic pigs and the development of coordinated co-stimulatory blockers have greatly facilitated progress in xenotransplantation research. We found that 'co-stimulation blockade', 'xenograft survival', 'pluripotent stem cell', 'translational research', and 'genetic engineering' were likely to be the focus of attention in the coming years. CONCLUSIONS: This study screened global publications related to xenogeneic kidney transplantation; analyzed their literature metrology characteristics; identified the most cited articles in the research field; understood the current situation, hot spots, and trends of global research; and provided future development directions for researchers and practitioners.

The mechanism of lncRNA SNHG1 in osteogenic differentiation via miR-497-5p/ HIF1AN axis.

The pivotal role of lncRNAs in osteoporosis progression and development necessitates a comprehensive exploration of the functional and precise molecular mechanisms underlying lncRNA SNHG1's regulation of osteoblast differentiation and calcification. The study involved inducing BMSCs cells to differentiate into osteoblasts, followed by transfections of miR-497-5p inhibitors, pcDNA3.1-SNHG1, sh-HIF1AN, miR-497-5p mimics, and respective negative controls into BMSCs. Quantitative PCR (qPCR) was employed to assess the expression of SNHG1 and miR-497-5p. Western Blotting was conducted to measure the levels of short stature-related transcription factor 2 (RUNX2), osteopontin (OPN), osteocalcin (OCN), and HIF1AN. Alkaline phosphatase (ALP) activity was determined using appropriate assay kits. Calcium nodule staining was performed through Alizarin red staining. Dual luciferase reporter gene assays were executed to validate the interaction between SNHG1 and miR-497-5p, as well as HIF1AN. Throughout osteogenic differentiation, there was a down-regulation of SNHG1 and HIF1AN, in contrast to an elevation in miR-497-5p levels. Direct interactions between miR-497-5p and both SNHG1 and HIF1AN were observed. Notably, SNHG1 exhibited the ability to modulate HIF1AN by influencing miR-497-5p, thereby inhibiting osteogenic differentiation. Functioning as a competitive endogenous RNA, lncRNA SNHG1 exerts an inhibitory influence on osteogenic differentiation via the miR-497-5p/HIF1AN axis. This highlights the potential for lncRNA SNHG1 to emerge as a promising therapeutic target for osteoporosis. The study's findings pave the way for a novel target strategy in the future treatment of osteoporosis.

Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature.

PURPOSE: Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. METHODS: The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group (n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group (n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. RESULTS: In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) µm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) µm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels. CONCLUSIONS: NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect.

Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.

Long Non-coding RNA SNHG1 Suppresses the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by Binding with HMGB1.

Osteoporosis (OP) has a significant detrimental impact on the health of the elder. Long-term clinical effectiveness of current drugs used for OP treatment is limited. Therefore, it is very important to explore novel treatment targets for OP. The expression of SNHG1, HMGB1, OCN and OPN in gene level was measured using RT-qPCR, and the protein expression was determined by Western blotting assay. The concentration of IL-1ß and IL-18 in supernatant of the bone marrow mesenchymal stem cells (BMSCs) was measured by ELISA. The interaction between SNHG1 and HMGB1 was confirmed by RNA pull down. Besides, alizarin red staining was performed to evaluate the differentiation of BMSCs into osteoblast. SNHG1 and HMGB1 were found to be upregulated in the serum of OP patients. During the osteogenic differentiation of BMSCs, the expression of osteoblastogenesis markers (OCN and OPN) and the activity of ALP were upregulated, while the expression levels of SNHG1 and HMGB1 were decreased in a time-dependent manner. In addition, the interaction between SNHG1 and HMGB1, expression of pyroptosis-associated factors (caspase-1 p20 and GSDMD-N), and secretion of IL-1ß and IL-18 were also decreased during osteogenic differentiation. Interestingly, increasing SNHG1 promoted HMGB1 expression, activated pyroptosis, but inhibited osteogenic differentiation. Silencing HMGB1 or inhibiting caspase-1 partially rescued the inhibitory effect of SNHG1 on osteogenic differentiation. Our findings indicate that SNHG1 suppresses the osteogenic differentiation of BMSCs by activating pyroptosis through interaction with HMGB1 and promotion of HMGB1 expression. Our work provides further evidence supporting SNHG1 acts as a potential target for OP treatment, and reveals for the first time that SNHG1 regulates osteogenic differentiation by affecting pyroptosis.

Bronchobiliary fistula caused after percutaneous transhepatic biliary drainage treatment: A case report.

RATIONALE: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the diagnosis and decompression of bile duct obstruction. However, it is associated with complications such as hemobilia, occlusion of drainage, bile leakage, and even bronchobiliary fistula (BBF). PATIENT CONCERNS AND DIAGNOSES: We herein describe a patient with a complication of BBF caused by long-term indwelling PTBD catheters. She underwent multiple operations including bilioenteric anastomosis, hepatic left lateral lobectomy, and long-term PTBD treatment. Her symptoms were mainly cough, fever, and yellow sputum and her diagnosis was confirmed by sputum culture (bilirubin detection was positive). INTERVENTIONS AND OUTCOMES: The patient recovered uneventfully by minimally invasive treatment, was discharged after 1 week of hospitalization, and the drainage tube was removed 2 weeks later. During 2 years of follow-up, no recurrence of BBF was observed. LESSONS: Patients with long-term indwelling PTBD catheters for biliary tract obstruction may lead to BBF. The treatment plan of BBF is tailored to the patient's individualized characteristics. And minimally invasive treatments might be an effective alternate way for the treatment of BBF. The accurate diagnosis, precision treatment, and multidisciplinary team play important roles in the treatment of BBF.

Mechanical Effects of Elastic Crystals Driven by Natural Sunlight and Force.

Flexible crystals that can capture solar energy and convert it into mechanical energy are promising for a wide range of applications such as information storage and actuators, but obtaining them remains a challenge. Herein, an elastic crystal of a barbiturate derivative was found to be an excellent candidate, demonstrating plastic bending behavior under natural sunlight irradiation. 1 H NMR and high-resolution mass spectrum data of microcrystals before and after light irradiation demonstrated that light-induced [2+2] cycloaddition was the driving force for the photomechanical effects. Interestingly, the crystals retained elastic bending even after light irradiation. This is the first report of flexible crystals that can be driven by natural sunlight and that have both photomechanical properties and elasticity. Furthermore, regulation of the passive light output direction of the crystals and transport of objects by applying mechanical forces and light was demonstrated.

A Bioresorbable and Conductive Scaffold Integrating Silicon Membranes for Peripheral Nerve Regeneration.

Peripheral nerve injury represents one of the most common types of traumatic damage, severely impairing motor and sensory functions, and posttraumatic nerve regeneration remains a major challenge. Electrical cues are critical bioactive factors that promote nerve regrowth, and bioartificial scaffolds incorporating conductive materials to enhance the endogenous electrical field have been demonstrated to be effective. The utilization of fully biodegradable scaffolds can eliminate material residues, and circumvent the need for secondary retrieval procedures. Here, a fully bioresorbable and conductive nerve scaffold integrating N-type silicon (Si) membranes is proposed, which can deliver both structural guidance and electrical cues for the repair of nerve defects. The entire scaffold is fully biodegradable, and the introduction of N-type Si can significantly promote the proliferation and production of neurotrophic factors of Schwann cells and enhance the calcium activity of dorsal root ganglion (DRG) neurons. The conductive scaffolds enable accelerated nerve regeneration and motor functional recovery in rodents with sciatic nerve transection injuries. This work sheds light on the advancement of bioresorbable and electrically active materials to achieve desirable neural interfaces and improved therapeutic outcomes, offering essential strategies for regenerative medicine.

Selenium Nanodots (SENDs) as Antioxidants and Antioxidant-Prodrugs to Rescue Islet ß Cells in Type 2 Diabetes Mellitus by Restoring Mitophagy and Alleviating Endoplasmic Reticulum Stress.

Preventing islet ß-cells death is crucial for treating type 2 diabetes mellitus (T2DM). Currently, clinical drugs are being developed to improve the quality of T2DM care and self-care, but drugs focused on reducing islets ß-cell death are lacking. Given that ß-cell death in T2DM is dominated ultimately by excessive reactive oxygen species (ROS), eliminating excessive ROS in ß-cells is a highly promising therapeutic strategy. Nevertheless, no antioxidants have been approved for T2DM therapy because most of them cannot meet the long-term and stable elimination of ROS in ß-cells without eliciting toxic side-effects. Here, it is proposed to restore the endogenous antioxidant capacity of ß-cells to efficiently prevent ß-cell death using selenium nanodots (SENDs), a prodrug of the antioxidant enzyme glutathione peroxidase 1 (GPX1). SENDs not only scavenge ROS effectively, but also "send" selenium precisely to ß-cells with ROS response to greatly enhance the antioxidant capacity of ß-cells by increasing GPX1 expression. Therefore, SENDs greatly rescue ß-cells by restoring mitophagy and alleviating endoplasmic reticulum stress (ERS), and demonstrate much stronger efficacy than the first-line drug metformin for T2DM treatment. Overall, this strategy highlights the great clinical application prospects of SENDs, offering a paradigm for an antioxidant enzyme prodrug for T2DM treatment.

Study on the association of the microstructure and bone metabolism in the osteoporotic femoral head.

BACKGROUND: We compared the bone microstructure and metabolism of the femoral heads in patients with osteoporosis (OP) and non-OP patients to investigate the pathologic mechanism of OP and guide clinical treatment. METHODS AND RESULTS: From January 2020 to June 2021, we obtained femoral head samples from 30 patients undergoing hip replacement due to femoral neck fracture. All patients were women aged approximately 67 to 80 years (mean age, 74 years). According to the dual-energy X-ray results, the femoral head samples were divided into the OP (T< - 2.5) and non-OP (T > - 1.5) groups. Microcomputed tomography scanning, bone metrology analysis, hematoxylin and eosin staining, and Masson's trichrome staining were used to compare the local bone trabecular microstructure changes. Quantitative reverse transcription PCR was performed to identify changes in the osteogenesis-related genes and the osteoclast-related genes in specific regions to reflect osteogenic and osteoclastic activities. Femoral heads with OP showed significant changes in the local bone microstructure. Bone density, bone volume fraction, and the number and thickness of the bone trabeculae decreased. Local bone metabolism was imbalanced in the areas with microstructural changes in femoral heads with OP, with increased osteoclast activity and decreased osteoblast activity. CONCLUSIONS: Deterioration of bone microstructure is closely related to abnormal bone metabolism associated with the activity of osteoblasts and osteoclasts in osteoporotic femoral heads. Promoting bone formation by improving local bone metabolism, enhancing osteogenic activity and inhibiting osteoclast activity may be a promising way of preventing local OP and osteoporotic fractures.

Development and validation of a nomogram to predict the risk of renal replacement therapy among acute kidney injury patients in intensive care unit.

BACKGROUND: There are no universally accepted indications to initiate renal replacement therapy (RRT) among patients with acute kidney injury (AKI). This study aimed to develop a nomogram to predict the risk of RRT among AKI patients in intensive care unit (ICU). METHODS: In this retrospective cohort study, we extracted AKI patients from Medical Information Mart for Intensive Care III (MIMIC-III) database. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%). Multivariable logistic regression based on Akaike information criterion was used to establish the nomogram. The discrimination and calibration of the nomogram were evaluated by Harrell's concordance index (C-index) and Hosmer-Lemeshow (HL) test. Decision curve analysis (DCA) was performed to evaluate clinical application. RESULTS: A total of 7413 critically ill patients with AKI were finally enrolled. 514 (6.9%) patients received RRT after ICU admission. 5194 (70%) patients were in the training cohort and 2219 (30%) patients were in the validation cohort. Nine variables, namely, age, hemoglobin, creatinine, blood urea nitrogen and lactate at AKI detection, comorbidity of congestive heart failure, AKI stage, and vasopressor use were included in the nomogram. The predictive model demonstrated satisfying discrimination and calibration with C-index of 0.938 (95% CI, 0.927-0.949; HL test, P = 0.430) in training set and 0.935 (95% CI, 0.919-0.951; HL test, P = 0.392) in validation set. DCA showed a positive net benefit of our nomogram. CONCLUSION: The nomogram developed in this study was highly accurate for RRT prediction with potential application value.

Deferoxamine Promotes Peripheral Nerve Regeneration by Enhancing Schwann Cell Function and Promoting Axon Regeneration of Dorsal Root Ganglion.

Deferoxamine (DFO) is a potent iron chelator for clinical treatment of various diseases. Recent studies have also shown its potential to promote vascular regeneration during peripheral nerve regeneration. However, the effect of DFO on the Schwann cell function and axon regeneration remains unclear. In this study, we investigated the effects of different concentrations of DFO on Schwann cell viability, proliferation, migration, expression of key functional genes, and axon regeneration of dorsal root ganglia (DRG) through a series of in vitro experiments. We found that DFO improves Schwann cell viability, proliferation, and migration in the early stages, with an optimal concentration of 25 µM. DFO also upregulates the expression of myelin-related genes and nerve growth-promoting factors in Schwann cells, while inhibiting the expression of Schwann cell dedifferentiation genes. Moreover, the appropriate concentration of DFO promotes axon regeneration in DRG. Our findings demonstrate that DFO, with suitable concentration and duration of action, can positively affect multiple stages of peripheral nerve regeneration, thereby improving the effectiveness of nerve injury repair. This study also enriches the theory of DFO promoting peripheral nerve regeneration and provides a basis for the design of sustained-release DFO nerve grafts.

Adenovirus-associated anti-miRNA-214 regulates bone metabolism and prevents local osteoporosis in rats.

Objective: We investigated the expression of miRNA-214 in human osteoporotic bone tissue and tested the utility of adeno-associated virus (AAV) expressing a miRNA-214 inhibitor in terms of preventing local osteoporosis of the femoral condyle in a rat model of osteoporosis. Methods: (1) Femoral heads of patients who underwent hip replacements at our hospital because of femoral neck fractures were collected and divided into osteoporosis and non-osteoporosis groups based on preoperative bone mineral density data. MiRNA-214 expression was detected in bone tissues exhibiting obvious bone microstructural changes in the two groups. (2) A total of 144 SD female rats were divided into four groups: the Control, Model, Negative control (Model + AAV), and Experimental (Model + anti-miRNA-214) groups. AAV-anti-miRNA-214 was injected locally into the rat femoral condyles; we explored whether this prevented or treated local osteoporosis. Results: (1) MiRNA-214 expression in the human femoral head was significantly increased in the osteoporosis group. (2) Compared to the Model and Model + AAV groups, the bone mineral density (BMD) and femoral condyle bone volume/tissue volume (BV/TV) ratio in the Model + anti-miRNA-214 group were significantly higher; in addition, the number (TB.N) and thickness (TB.Th) of the trabecular bones were increased (all p < 0.05). MiRNA-214 expression in the femoral condyles of the Model + anti-miRNA-214 group was significantly higher than that in the other groups. The expression levels of the osteogenesis-related genes Alp, Bglap, and Col1α1 increased, while those of the osteoclast-related genes NFATc1, Acp5, Ctsk, Mmp9, and Clcn7 decreased. Conclusion: AAV-anti-miRNA-214 promoted osteoblast activity and inhibited osteoclast activity in the femoral condyles of osteoporotic rats, improving bone metabolism and slowing osteoporosis progression.

Association of geriatric nutritional risk index with all-cause hospital mortality among elderly patients in intensive care unit.

Background: Malnutrition is associated with poor outcomes for geriatric patients in intensive care unit (ICU). It is important to identify patients at risk of malnutrition and provide individual nutrition support. The assessment of malnutrition risk is not easy for these patients due to their cognitive impairment. Geriatric nutrition risk index (GNRI) is a simple and objective scoring tool to evaluate the risk of malnutrition in elderly patients. In this study, we aimed to see whether GNRI score was appropriate to predict clinical outcomes among geriatric patients in the setting of ICU. Materials and methods: Elderly patients with age ≥ 65 years were extracted from Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Categories based on GNRI were classified as major risk (GNRI <82), moderate risk (GNRI 82 to <92), low risk (GNRI 92 to ≤98), and no risk (GNRI >98). The primary outcome was all-cause hospital mortality. Multivariable Cox proportional hazards regression models and restricted cubic spline were used to investigate associations of GNRI with hospital mortality, respectively. A two-piecewise linear regression model was applied to examine the inflection point of GNRI on hospital mortality. To reduce selection bias, propensity score matching (PSM) was used in a 1:1 ratio. Results: A total of 3,696 geriatric patients were finally included with median age 75 (69, 81) years. The prevalence of major risk was 28.6%. In the fully adjusted model, GNRI categories featured a negative trend with hospital mortality (p for trend = 0.037). Restricted cubic spline analysis demonstrated an L-shaped relationship between GNRI and hospital mortality before and after matching. The inflection point was 78.7. At the left side of inflection point, GNRI levels were significantly negatively associated with hospital mortality (HR = 0.96, 95% CI: 0.94-0.98; p < 0.001) and featured no significant relations at the right side. Multiple linear regression also showed that GNRI was negatively associated with length of stay in hospital. Conclusion: The major risk of malnutrition defined by GNRI was able to predict poor prognosis for geriatric patients admitted to ICU.