Risk factors for infection in patients undergoing shoulder arthroscopy: A Systematic Review and Meta-analysis.

PURPOSE: We conducted a meta-analysis to determine the risk of infection following shoulder arthroscopy and to identify risk factors for infection. METHODS: We systematically searched the PubMed/Medline, Embase and Cochrane Library databases, as well as the reference lists of previous systematic reviews and meta-analyses; manual searches were also performed. A random-effects model was employed to estimate pooled ORs, based on sample size, the p value of Egger's test and heterogeneity among studies. RESULTS: Of the 29,342 articles screened, 16 retrospective studies comprising 74,759 patients were included. High-quality evidence showed that patients with diabetes (OR, 1.30; 95% CI, 1.20-1.41) or hypertension (OR, 1.26;95% CI, 1.10-1.44) had a higher risk of infection, while moderate quality evidence showed that patients with obesity (BMI ≥30 kg/m2) (OR, 1.42;95% CI, 1.28-1.57), those who were male (OR, 1.65;95% CI, 1.12-2.44), those who had an ASA class ≥3 (OR, 2.02;95% CI,1.02-3.99) and those who had a history of smoking (OR, 2.44;95% CI, 1.39-4.28) had a higher risk of infection. The meta-analysis revealed that there was no association between age, time of surgery, or alcohol consumption and infection. CONCLUSIONS: This meta-analysis identified six significant risk factors for infection following shoulder arthroscopy, including diabetes, obesity, hypertension, male sex, ASA class, history of smoking. These patient-related risk factors may help identify postoperative patients at higher risk for infection following shoulder arthroscopy. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and Level IV studies. TRIAL REGISTRATION NUMBER: The review protocol was registered in PROSPERO. Unique Identifying Number (UIN) is "CRD42023463316".

The impact of perioperative nonsteroidal anti-inflammatory drugs on the postoperative outcomes of spinal surgery: a meta-analysis of 23 randomized controlled trials.

In recent years, nonsteroidal anti-inflammatory drug (NSAIDs), which are considered to affect the prognosis of spinal surgery, have been widely used in perioperative analgesia in spinal surgery, but the relationship between these two factors remains unclear. The purpose of this study was to explore the effect of perioperative use of NSAIDs on the prognosis of patients treated with spinal surgery. We systematically searched PubMed, Embase, and Cochrane Library for relevant articles published on or before July 14, 2023. We used a random-effect model for the meta-analysis to calculate the standardized mean difference (SMD) with a 95% confidence interval (CI). Sensitivity analyses were conducted to analyze stability. A total of 23 randomized clinical trials including 1457 participants met the inclusion criteria. Meta-analysis showed that NSAIDs were significantly associated with postoperative morphine use (mg) (SMD = -0.90, 95% CI -1.12 to -0.68) and postoperative pain (SMD = -0.71, 95% CI -0.85 to -0.58). These results were further confirmed by the trim-and-fill procedure and leave-one-out sensitivity analyses. The current study shows that perioperative use of NSAIDs appears to be an important factor in reducing postoperative pain and morphine use in patients undergoing spinal surgery. However, well-designed, high-quality randomized controlled trials (RCTs) are still required.

Noninterportal capsulotomy of hip arthroscopy showed improved outcomes in borderline hip dysplasia: A retrospective study with minimum 2-year follow-up.

PURPOSE: The present study aimed to evaluate the functional outcomes of hip arthroscopy using a noninterportal capsulotomy technique to address labral tears in patients with borderline hip dysplasia (BHD). Additionally, we also compared these outcomes with those of patients with BHD who underwent the standard repaired interportal capsulotomy (RIPC) arthroscopy. METHODS: Data from patients with BHD were retrieved from a database of patients who underwent arthroscopic hip surgery with noninterportal capsulotomy or RIPC to treat labral tears between January 2014 and December 2020. Data collected included both pre- and postoperative patient-reported outcomes (PROs). RESULTS: A total of 58 patients (noninterportal capsulotomy, n = 37; RIPC, n = 21) with a mean age of 30.9 ± 5.6 and 28.6 ± 5.5 years, respectively, met the inclusion criteria. All of the patients underwent a minimal 2-year follow-up. The mean lateral centre-edge angle was 23.3 ± 1.2° in the noninterportal capsulotomy group and 23.7 ± 1.0° in the RIPC group, with no significant difference. The PROs improved from the preoperative to the latest follow-up, with a p < 0.001. There were no differences between the groups. CONCLUSION: Using strict patient selection criteria, hip arthroscopy with noninterportal capsulotomy demonstrated significant pre- to postoperative improvements in patients with BHD and achieved results comparable to those from hip arthroscopy with RIPC. LEVEL OF EVIDENCE: Level III.

MSC-derived mitochondria promote axonal regeneration via Atf3 gene up-regulation by ROS induced DNA double strand breaks at transcription initiation region.

BACKGROUND: The repair of peripheral nerve injury poses a clinical challenge, necessitating further investigation into novel therapeutic approaches. In recent years, bone marrow mesenchymal stromal cell (MSC)-derived mitochondrial transfer has emerged as a promising therapy for cellular injury, with reported applications in central nerve injury. However, its potential therapeutic effect on peripheral nerve injury remains unclear. METHODS: We established a mouse sciatic nerve crush injury model. Mitochondria extracted from MSCs were intraneurally injected into the injured sciatic nerves. Axonal regeneration was observed through whole-mount nerve imaging. The dorsal root ganglions (DRGs) corresponding to the injured nerve were harvested to test the gene expression, reactive oxygen species (ROS) levels, as well as the degree and location of DNA double strand breaks (DSBs). RESULTS: The in vivo experiments showed that the mitochondrial injection therapy effectively promoted axon regeneration in injured sciatic nerves. Four days after injection of fluorescently labeled mitochondria into the injured nerves, fluorescently labeled mitochondria were detected in the corresponding DRGs. RNA-seq and qPCR results showed that the mitochondrial injection therapy enhanced the expression of Atf3 and other regeneration-associated genes in DRG neurons. Knocking down of Atf3 in DRGs by siRNA could diminish the therapeutic effect of mitochondrial injection. Subsequent experiments showed that mitochondrial injection therapy could increase the levels of ROS and DSBs in injury-associated DRG neurons, with this increase being correlated with Atf3 expression. ChIP and Co-IP experiments revealed an elevation of DSB levels within the transcription initiation region of the Atf3 gene following mitochondrial injection therapy, while also demonstrating a spatial proximity between mitochondria-induced DSBs and CTCF binding sites. CONCLUSION: These findings suggest that MSC-derived mitochondria injected into the injured nerves can be retrogradely transferred to DRG neuron somas via axoplasmic transport, and increase the DSBs at the transcription initiation regions of the Atf3 gene through ROS accumulation, which rapidly release the CTCF-mediated topological constraints on chromatin interactions. This process may enhance spatial interactions between the Atf3 promoter and enhancer, ultimately promoting Atf3 expression. The up-regulation of Atf3 induced by mitochondria further promotes the expression of downstream regeneration-associated genes and facilitates axon regeneration.

Long noncoding RNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote lung carcinogenesis.

Hexavalent chromium [Cr(VI)] is a common environmental pollutant and chronic exposure to Cr(VI) causes lung cancer in humans, however, the mechanism of Cr(VI) carcinogenesis has not been well understood. Lung cancer is the leading cause of cancer-related death, although the mechanisms of how lung cancer develops and progresses have been poorly understood. While long non-coding RNAs (lncRNAs) are found abnormally expressed in cancer, how dysregulated lncRNAs contribute to carcinogenesis remains largely unknown. The goal of this study is to investigate the mechanism of Cr(VI)-induced lung carcinogenesis focusing on the role of the lncRNA ABHD11 antisense RNA 1 (tail to tail) (ABHD11-AS1). It was found that the lncRNA ABHD11-AS1 expression levels are up-regulated in chronic Cr(VI) exposure-transformed human bronchial epithelial cells, chronically Cr(VI)-exposed mouse lung tissues, and human lung cancer cells as well. Bioinformatics analysis revealed that ABHD11-AS1 levels are up-regulated in lung adenocarcinomas (LUADs) tissues and associated with worse overall survival of LUAD patients but not in lung squamous cell carcinomas. It was further determined that up-regulation of ABHD11-AS1 expression plays an important role in chronic Cr(VI) exposure-induced cell malignant transformation and tumorigenesis, and the stemness of human lung cancer cells. Mechanistically, it was found that ABHD11-AS1 directly binds SART3 (spliceosome associated factor 3, U4/U6 recycling protein). The interaction of ABHD11-AS1 with SART3 promotes USP15 (ubiquitin specific peptidase 15) nuclear localization. Nuclear localized USP15 interacts with pre-mRNA processing factor 19 (PRPF19) to increase CD44 RNA alternative splicing activating ß-catenin and enhancing cancer stemness. Together, these findings indicate that lncRNA ABHD11-AS1 interacts with SART3 and regulates CD44 RNA alternative splicing to promote cell malignant transformation and lung carcinogenesis.

Enhanced Osteolysis Targeted Therapy through Fusion of Exosomes Derived from M2 Macrophages and Bone Marrow Mesenchymal Stem Cells: Modulating Macrophage Polarization.

Aseptic loosening of prostheses is a highly researched topic, and wear particle-induced macrophage polarization is a significant cause of peri-prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2-Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2-Exos and BMSCs-Exos fused exosomes (M2-BMSCs-Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2-BMSCs-Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2-BMSCs-Exos can be used as a precise and reliable molecular drug for peri-prosthetic osteolysis. Fused exosomes M2-BMSCs-Exos  were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes.

[A multicenter randomized controlled trial of domestic robot-assisted and conventional total knee arthroplasty].

Objective: To investigate the accuracy, safety, and short-term effectiveness of a domestic robot-assisted system in total knee arthroplasty (TKA) by a multicenter randomized controlled trial. Methods: Between December 2021 and February 2023, 138 patients with knee osteoarthritis who received TKA in 5 clinical centers were prospectively collected, and 134 patients met the inclusion criteria were randomly assigned to either a trial group ( n=68) or a control group ( n=66). Seven patients had lost follow-up and missing data, so they were excluded and the remaining 127 patients were included for analysis, including 66 patients in the trial group and 61 patients in the control group. There was no significant difference ( P>0.05) in gender, age, body mass index, side, duration of osteoarthritis, Kellgren-Lawrence grading, preoperative Knee Society Score (KSS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score between the two groups. The trial group completed the TKA by domestic robot-assisted osteotomy according to the preoperative CT-based surgical planning. The control group was performed by traditional osteotomy plate combined with soft tissue release. Total operation time, osteotomy time of femoral/tibial side, intraoperative blood loss, and postoperative complications were recorded and compared between the two groups. The radiographs were taken at 5 and 90 days after operation, and hip-knee-ankle angle (HKA), lateral distal angle of femur (LDFA), and posterior tibial slope (PTS) were measured. The difference between the measured values of the above indexes at two time points after operation and the preoperative planning target values was calculated, and the absolute value (absolute error) was taken for comparison between the two groups. The postoperative recovery of lower limb alignment was judged and the accuracy was calculated. KSS score and WOMAC score were used to evaluate the knee joint function of patients before operation and at 90 days after operation. The improvement rates of KSS score and WOMAC score were calculated. The function, stability, and convenience of the robot-assisted system were evaluated by the surgeons. Results: The total operation time and femoral osteotomy time of the trial group were significantly longer than those of the control group ( P<0.05). There was no significant difference in the tibial osteotomy time and the amount of intraoperative blood loss between the two groups ( P>0.05). The incisions of both groups healed by first intention after operation, and there was no infection around the prosthesis. Nine patients in the trial group and 8 in the control group developed lower extremity vascular thrombosis, all of which were calf intermuscular venous thrombosis, and there was no significant difference in the incidence of complications ( P>0.05). All patients were followed up 90 days. There was no significant difference in KSS score and WOMAC score between the two groups at 90 days after operation ( P>0.05). There was significant difference in the improvement rate of KSS score between the two groups ( P<0.05), while there was no significant difference in the improvement rate of WOMAC score between the two groups ( P>0.05). Radiological results showed that the absolute errors of HKA and LDFA in the trial group were significantly smaller than those in the control group at 5 and 90 days after operation ( P<0.05), and the recovery accuracy of lower limb alignment was significantly higher than that in control group ( P<0.05). The absolute error of PTS in the trial group was significantly smaller than that in the control group at 5 days after operation ( P<0.05), but there was no significant difference at 90 days between the two groups ( P>0.05). The functional satisfaction rate of the robot-assisted system was 98.5% (65/66), and the satisfaction rates of stability and convenience were 100% (66/66). Conclusion: Domestic robot-assisted TKA is a safe and effective surgical treatment for knee osteoarthritis, which can achieve favorable lower limb alignment reconstruction, precise implant of prosthesis, and satisfactory functional recovery.

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis.

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

Co-exposure to low-dose lead, cadmium, and mercury promotes memory deficits in rats: Insights from the dynamics of dendritic spine pruning in brain development.

Lead (Pb), cadmium (Cd), and mercury (Hg) are environmentally toxic heavy metals that can be simultaneously detected at low levels in the blood of the general population. Although our previous studies have demonstrated neurodevelopmental toxicity upon co-exposure to these heavy metals at these low levels, the precise mechanisms remain largely unknown. Dendritic spines are the structural foundation of memory and undergo significant dynamic changes during development. This study focused on the dynamics of dendritic spines during brain development following Pb, Cd, and Hg co-exposure-induced memory impairment. First, the dynamic characteristics of dendritic spines in the prefrontal cortex were observed throughout the life cycle of normal rats. We observed that dendritic spines increased rapidly from birth to their peak value at weaning, followed by significant pruning and a decrease during adolescence. Dendritic spines tended to be stable until their loss in old age. Subsequently, a rat model of low-dose Pb, Cd, and Hg co-exposure from embryo to adolescence was established. The results showed that exposure to low doses of heavy metals equivalent to those detected in the blood of the general population impaired spatial memory and altered the dynamics of dendritic spine pruning from weaning to adolescence. Proteomic analysis of brain and blood samples suggested that differentially expressed proteins upon heavy metal exposure were enriched in dendritic spine-related cytoskeletal regulation and axon guidance signaling pathways and that cofilin was enriched in both of these pathways. Further experiments confirmed that heavy metal exposure altered actin cytoskeleton dynamics and disturbed the dendritic spine pruning-related LIM domain kinase 1-cofilin pathway in the rat prefrontal cortex. Our findings demonstrate that low-dose Pb, Cd, and Hg co-exposure may promote memory impairment by perturbing dendritic spine dynamics through dendritic spine pruning-related signaling pathways.

An Association between Decreased Small Intestinal RNA Modification and Disturbed Glucagon-like Peptide-1 Secretion under High-Fat Diet Stress.

Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known "writers", mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.

Difunctional Magnetic Nanoparticles Employed in Immunochromatographic Assay for Rapid and Quantitative Detection of Carcinoembryonic Antigen.

Immunochromatographic assay (ICA) plays an important role in in vitro diagnostics because of its simpleness, convenience, fastness, sensitivity, accuracy, and low cost. The employment of magnetic nanoparticles (MNPs), possessing both excellent optical properties and magnetic separation functions, can effectively promote the performances of ICA. In this study, an ICA based on MNPs (MNP-ICA) has been successfully developed for the sensitive detection of carcinoembryonic antigen (CEA). The magnetic probes were prepared by covalently conjugating carboxylated MNPs with the specific monoclonal antibody against CEA, which were not only employed to enrich and extract CEA from serum samples under an external magnetic field but also used as a signal output with its inherent optical property. Under the optimal parameters, the limit of detection (LOD) for qualitative detection with naked eyes was 1.0 ng/mL, and the quantitative detection could be realized with the help of a portable optical reader, indicating that the ratio of optical signal intensity correlated well with CEA concentration ranging from 1.0 ng/mL to 64.0 ng/mL (R2 = 0.9997). Additionally, method comparison demonstrated that the magnetic probes were beneficial for sensitivity improvement due to the matrix effect reduction after magnetic separation, and the MNP-ICA is eight times higher sensitive than ICA based on colloidal gold nanoparticles. The developed MNP-ICA will provide sensitive, convenient, and efficient technical support for biomarkers rapid screening in cancer diagnosis and prognosis.

Hmga1-overexpressing lentivirus protects against osteoporosis by activating the Wnt/ß-catenin pathway in the osteogenic differentiation of BMSCs.

Postmenopausal osteoporosis is associated with bone formation inhibition mediated by the impaired osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs). However, identifying and confirming the essential genes in the osteogenic differentiation of BMSCs and osteoporosis remain challenging. The study aimed at revealing the key gene that regulated osteogenic differentiation of BMSCs and led to osteoporosis, thus exploring its therapeutic effect in osteoporosis. In the present study, six essential genes related to the osteogenic differentiation of BMSCs and osteoporosis were identified, namely, fibrillin 2 (Fbn2), leucine-rich repeat-containing 17 (Lrrc17), heat shock protein b7 (Hspb7), high mobility group AT-hook 1 (Hmga1), nexilin F-actin-binding protein (Nexn), and endothelial cell-specific molecule 1 (Esm1). Furthermore, the in vivo and in vitro experiments showed that Hmga1 expression was increased during the osteogenic differentiation of rat BMSCs, while Hmga1 expression was decreased in the bone tissue of ovariectomized (OVX) rats. Moreover, the expression of osteogenic differentiation-related genes, the activity of alkaline phosphatase (ALP), and the number of mineralized nodules were increased after Hmga1 overexpression, which was partially reversed by a Wnt signaling inhibitor (DKK1). In addition, after injecting Hmga1-overexpressing lentivirus into the bone marrow cavity of OVX rats, the bone loss, and osteogenic differentiation inhibition of BMSCs in OVX rats were partially reversed, while osteoclast differentiation promotion of BMSCs in OVX rats was unaffected. Taken together, the present study confirms that Hmga1 prevents OVX-induced bone loss by the Wnt signaling pathway and reveals that Hmga1 is a potential gene therapeutic target for postmenopausal osteoporosis.

Association between input/weight ratio and acute kidney injury in obese critical ill patients: a propensity analysis of multicenter clinical databases.

Rehydration volume may be underestimated in obese critically ill patients, which can lead to acute kidney injury (AKI). This study aimed to investigate the association between input/weight ratio (IWR) and AKI risk in obese critical patients. This retrospective observational study analyzed data from three large open databases. Patients were divided into lean and obese groups and matched 1:1 based on age, sex, APACHE II score, SOFA score, sepsis status, mechanical ventilation status, renal replacement therapy status, and hospital type. The exposure of interest was the mean IWR during the first three ICU admission days. The primary outcome was the incidence of AKI within 28 days after ICU admission. Cox regression analysis was used to evaluate the association between IWR and AKI risk. A total of 82,031 eligible patients were included in the study, with 25,427 obese patients matched with 25,427 lean patients. The IWRs were significantly lower in the obese groups in both the unmatched cohort (35.85 ± 19.05 vs. 46.01 ± 30.43 ml/kg, p < 0.01) and the matched cohort (36.13 ± 19.16 vs. 47.34 ± 31.13 ml/kg, p < 0.01). An increase in IWR was significantly associated with decreased creatinine levels, increased urine output and a lower AKI risk. The interaction terms of IWR and obesity were significantly associated with decreased AKI incidence in both the unmatched cohort (hazard ratio [HR] = 0.97, 95% CI 0.96-0.97, p < 0.01) and the matched cohort (HR = 0.97, 95% CI 0.96-0.97, p < 0.01). Inadequate rehydration of patients with obesity may contribute to an increased risk of AKI in patients with obesity. These results highlight the need for better rehydration management in patients with obesity.

Associations of concomitant retinopathy and depression with mortality in a nationally representative population.

OBJECTIVE: To evaluate the interaction effects between retinopathy and depression on mortality risks in genral population and subpopulation with diabetes. METHODS: Prospective analyses were conducted on data from the National Health and Nutrition Examination Surveys study. Associations of retinopathy, depression and their interaction with all-cause, cardiovascular disease (CVD)-specific, cancer-specific and other-specific mortality risk were estimated using Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS: Among 5367 participants, the weighted prevalence of retinopathy and depression was 9.6 % and 7.1 %, respectively. After a follow-up period of 12.1 years, 1295 deaths (17.3 %) occurred. Retinopathy was associated with an increased risk of all-cause (hazard ratio [HR]; 95 % confidence interval [CI]) (1.47; 1.27-1.71), CVD-specific (1.87; 1.45-2.41), and other-specific (1.43; 1.14-1.79) mortality. Similar relationship was observed between depression and all-cause mortality (1.24; 1.02-1.52). Retinopathy and depression had a positive multiplicative and additive interaction effect on all-cause (Pinteraction = 0.015; relative excess risk of interaction [RERI] 1.30; 95 % CI 0.15-2.45) and CVD-specific mortality (Pinteraction = 0.042; RERI 2.65; 95 % CI -0.12-5.42). Concomitant retinopathy and depression was more markedly associated with all-cause (2.86; 1.91-4.28), CVD-specific (4.70; 2.57-8.62), and other-specific mortality risks (2.18; 1.14-4.15) compared to those without retinopathy and depression. These associations were more pronounced in the diabetic participants. CONCLUSIONS: The co-occurrence of retinopathy and depression increases the risk of all-cause and CVD-specific mortality among middle-aged and older adults in the United States, especially in population with diabetes. Focus on diabetic patients and active evaluation and intervention of retinopathy with depression may improve their quality of life and mortality outcomes.

The Systemic Inflammation Score is Associated with the Survival of Patients with Prostate Cancer.

Background: The systemic inflammation score (SIS) based on the albumin (Alb) level and lymphocyte-to-monocyte ratio (LMR), has been associated with survival in some cancers. However, its prognostic role in prostate cancer (PCa) remains unclear. Methods: The associations between the SIS and the clinicopathological features of PCa were evaluated. The correlations between the SIS and overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and the Log rank test. Univariate and multivariate Cox analyses were conducted to determine the prognostic factors for PCa. Hazard ratios and 95% confidence intervals were calculated. Results: A total of 253 patients with PCa were included in this study. The Kaplan-Meier analysis and Log rank test suggested that patients with a higher Alb level, higher LMR, or a lower SIS had better 5-year OS and PFS compared with patients with a lower Alb level or lower LMR or higher SIS. Univariate and multivariate Cox analyses showed that drinking, prostate-specific antigen level >100 ng/mL, and neutrophil-to-lymphocyte ratio >2.09 were significant prognostic factors for OS and PFS in patients with PCa. Nomograms for 5-year OS and PFS were established with concordance index values of 0.888 and 0.824, respectively. The calibration curve was consistent between the actual observations and the prediction nomogram for OS and PFS probability at 5 years. Conclusion: A high SIS is associated with unfavorable survival in patients with PCa. The SIS serves as a novel independent prognostic factor for OS in patients with PCa.

Cognitive outcomes caused by low-level lead, cadmium, and mercury mixture exposure at distinct phases of brain development.

Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body. Long-term and low-level ingestion of these toxic heavy metals may affect brain development and cognition. However, the neurotoxic effects of exposure to lead, cadmium, and mercury mixture (Pb + Cd + Hg) at different stages of brain development are rarely elucidated. In this study, different doses of low-level Pb + Cd + Hg were administered to Sprague-Dawley rats via drinking water during the critical stage of brain development, late stage, and after maturation, respectively. Our findings showed that Pb + Cd + Hg exposure decreased the density of memory- and learning-related dendritic spines in the hippocampus during the critical period of brain development, resulting in hippocampus-dependent spatial memory deficits. Only the density of learning-related dendritic spines was reduced during the late phase of brain development and a higher-dose of Pb + Cd + Hg exposure was required, which led to hippocampus-independent spatial memory abnormalities. Exposure to Pb + Cd + Hg after brain maturation revealed no significant change in dendritic spines or cognitive function. Further molecular analysis indicated that morphological and functional changes caused by Pb + Cd + Hg exposure during the critical phase were associated with PSD95 and GluA1 dysregulation. Collectively, the effects of Pb + Cd + Hg on cognition varied depending on the brain development stages.

Targeted therapy for peri-prosthetic osteolysis using macrophage membrane-encapsulated human urine-derived stem cell extracellular vesicles.

Aseptic loosening of the prosthesis is a severe complication after joint replacement. It is of great practical significance and social value to discover the prevention and treatment strategies for this condition. Exosomes from urine-derived stem cells (Exos) have great potential in promoting bone repair, reconstruction, and regulating bone metabolism. However, they are easily eliminated by macrophages and incapable of targeting the osteolysis zone. In this study, based on macrophage "homing" into periprosthetic osteolysis region and cell membrane encapsulating nanotechnology, exosomes from urine-derived stem cells were encapsulated with macrophage membrane (MM) to prevent periprosthetic osteolysis. We found that macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effectiveness of Exos, which alleviated wear particles-induced calvarial osteolysis. Furthermore, MM-Exos could provide immunological camouflage and allow the Exos to avoid phagocytosis by macrophages and stimulate cellular uptake by bone marrow-derived stem cells (BMSCs). Therefore, we demonstrated the unique ability of the macrophage membrane as a targeted transport of exosomes from urine-derived stem cells for the prevention and treatment of periprosthetic osteolysis. These biomimetic nanoparticles provided a new therapeutic exosome delivery system for preventing wear particles-induced osteolysis. STATEMENT OF SIGNIFICANCE: Macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effect of Exos on peri­prosthetic osteolysis prevention. MM-Exos could allow the Exos to avoid phagocytosis by macrophages and promote the uptake of Exos by BMSCs.

Pregnancy and lactation mixed exposure to lead, cadmium, and mercury alters maternal-offspring single heavy metal load: A factorial design.

Environmental exposure to heavy metal mixture of lead (Pb), cadmium (Cd), and mercury (Hg) would induce hazardous health effects. However, there is a paucity of data on how exposure to heavy metal mixture alters the metabolic dynamics of individual metals. Considering that the dose plays a key role in determining the toxicity of heavy metals, we performed a factorial design with three heavy metals (Pb, Cd, and Hg) at low exposure levels. Female rats were exposed to Pb, Cd, and (or) Hg from successful mating until pup weaning. Their concentrations in maternal blood, breast milk, and postnatal day 0 (PND0) and PND21 offspring blood and whole brain were measured. Using ANOVA analysis, Pearson correlation, and structural equation model, we demonstrated the complex interactions among heavy metals during their absorption, mother-offspring transport, and target organ accumulation. Among all the explored samples, almost all the highest Pb, Cd, and Hg levels were observed in their respective single heavy metal exposure groups. In addition, Hg was found could antagonize the transport of Pb or Cd, when they cross the placental barrier and blood-brain barriers (BBB). However, the effect of Hg no longer presented when they are absorbed through the digestive system. The antagonistic effect of Pb on Cd was observed when they cross the placental barrier. In addition, Cd was also found to compete the transport pathway of Pb when they cross the BBB after birth. Compared to Pb and Hg, we found that the transport efficiency of Cd in the digestive system was lower, whereas the chelation of Cd by the placental barrier was better. This preliminary information may help researchers to explore the mechanism underlying the hazardous effects of heavy metal mixture exposure, or for regulatory agencies to revise guidelines for heavy metal exposure.

Regulating the Pt-MnO2 Interaction and Interface for Room Temperature Formaldehyde Oxidation.

Formaldehyde (HCHO) is a hazardous pollutant in indoor space for humans because of its carcinogenicity. Removing the pollutant by MnO2-based catalysts is of great interest because of their high oxidation performance at room temperature. In this work, we regulate the Pt-MnO2 (MnO2 = manganese oxide) interaction and interface by embedding Pt in MnO2 (Pt-in-MnO2) and by dispersing Pt on MnO2 (Pt-on-MnO2) for HCHO oxidation over Pt-MnO2 catalysts with trace Pt loading of 0.01 wt %. In comparison to the Pt-in-MnO2 catalyst, the Pt-on-MnO2 catalyst has a higher Brunauer-Emmett-Teller surface area, a more active lattice oxygen, more oxygen vacancy activating more dioxygen molecules, more exposed Pt atoms, and noninternal diffusion of mass transfer, which contribute to the higher HCHO oxidation performance. The HCHO oxidation performance is stable over the Pt-MnO2 catalysts under high space velocity and high moisture humidity conditions, showing great potential for practical applications. This work demonstrates a more effective Pt-dispersed MnO2 catalyst than Pt-embedded MnO2 catalyst for HCHO oxidation, providing universally important guidance for metal-support interaction and interface regulation for oxidation reactions.

Hypermethylation of microRNA-497-3p contributes to progression of thyroid cancer through activation of PAK1/ß-catenin.

MicroRNA-497 (miR-497) has been reported to be a tumor-suppressive miRNA in thyroid cancer (TC), yet the mechanism is not clearly defined. In this study, we aim to determine the mechanism by which miR-497-3p affects the progression of TC. After characterization of low miR-497-3p expression pattern in TC and normal tissues, we assessed the correlation between miR-497-3p expression and clinicopathological features of TC patients. Its low expression shared associations with advanced tumor stage and lymph node metastasis. ChIP and methylation-specific PCR provided data showing that downregulation of miR-497-3p in TC tissues was induced by DNA methyltransferase-mediated hypermethylation. By performing dual-luciferase reporter assay, we identified that miR-497-3p targeted PAK1 while PAK1 could inhibit ß-catenin expression. Through this mechanism, miR-497-3p exerted the anti-proliferative, anti-invasive, pro-apoptotic, and anti-tumorigenic effects on TC cells on the strength of the results from gain-of-function and rescue experiments. This study suggested that hypermethylation of miR-497-3p resulted in upregulation of ß-catenin dependent on PAK1 and contributed to cancer progression in TC, which highlighted one of miR-mediated tumorigenic mechanism.