Liver as a new target organ in Alzheimer's disease: insight from cholesterol metabolism and its role in amyloid-beta clearance.

Alzheimer's disease, the primary cause of dementia, is characterized by neuropathologies, such as amyloid plaques, synaptic and neuronal degeneration, and neurofibrillary tangles. Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs, targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment. Metabolic abnormalities are commonly observed in patients with Alzheimer's disease. The liver is the primary peripheral organ involved in amyloid-beta metabolism, playing a crucial role in the pathophysiology of Alzheimer's disease. Notably, impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease. In this review, we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism. Furthermore, we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Acromioplasty combined with arthroscopic rotator cuff repair can reduce the risk of reoperation: a systematic review and meta-analysis.

BACKGROUND: Whether to perform acromioplasty in arthroscopic rotator cuff repair (ARCR) is controversial, and the optimal surgical approach for rotator cuff tear repair is unknown. The purpose of this study was to compare the reoperation rate, retear rate and patient-reported outcomes (PROs) of ARCR with those of ARCR combined with acromioplasty (ARCR-A). METHODS: PubMed, Embase and Cochrane Library were searched for relevant literature dated between database inception and 4 December 2023. The primary outcomes of this study were the reoperation rate and the retear rate. The secondary outcomes were PROs, including the visual analogue scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, the University of California-Los Angeles (UCLA) score, the Constant score and the Western Ontario Rotator Cuff (WORC) score. The quality of the included studies was evaluated by using the risk of bias assessment tool. RevMan 5.3 software was used for meta-analysis. Fixed (I2 <50%) or random (I2 ≥50%) effects models were applied to calculate the effect size. RESULTS: Meta-analysis revealed that ARCR-A had a lower reoperation rate (OR = 0.35, 95%CI: 0.15-0.85, p = 0.02), but the difference in the retear rate between ARCR-A and ARCR was not significant (p = 0.25). In type 2 acromion patients, the reoperation rate was not significantly different between ARCR and ARCR-A (p = 0.12), but, for type 3 acromion patients, the retear rate was lower for ARCR-A than for ARCR (OR = 0.12, 95%CI: 0.01-0.94, p = 0.04). There were statistically significant differences in the 6-month postoperative Constant scores (p < 0.001), VAS pain scores (p = 0.003) 12-month postoperative ASES scores (p = 0.02) and 24-month postoperative WORC scores (p = 0.04), but these differences were not clinically significant. CONCLUSIONS: Combining ARCR with acromioplasty can reduce the rate of reoperation, especially in patients with type 3 acromion, but it provides no clinically important change in the retear rate and postoperative PRO compared with ARCR.

Hyperthyroidism increases the risk of osteoarthritis in individuals aged 60-80 years.

To elucidate the currently unknown relationship between hyperthyroidism and osteoarthritis (OA). During 2007-2012, 7,433 participants (hyperthyroidism patients = 125; OA patients = 675) were included in the National Health and Nutrition Examination Survey database. We used a weighted multivariable-adjusted logistic regression analysis to assess the association between hyperthyroidism and OA. We also assessed the causality of that relationship using publicly available genome-wide association study data and three Mendelian randomization (MR) analysis methods. The heterogeneity test, pleiotropy test, and leave-one-out tests were used for sensitivity analysis. In this cross-sectional study, after adjusting for potential confounding factors, we found that hyperthyroidism significantly (P = 0.018) increased the risk of OA (odds ratio [OR] = 2.23, 95% confidence interval [CI] = 1.2-4.17). Age-stratified analysis revealed that hyperthyroidism was associated with a greater risk of OA in the 60-80-year-old age group (OR = 2.86, 95% CI = 1.46-5.59, P = 0.002), with no significant association in the 18-59-year-old age group (all P > 0.05). The results of the inverse-variance weighting (IVW) analysis showed that hyperthyroidism increased the risk of OA (OR = 1.23, 95% CI = 1.04-1.46; P = 0.017). The weighted median estimator (WME) and MR-Egger method also confirmed this causal association (OR = 1.27 and OR = 1.32, respectively). The sensitivity analysis results confirmed the reliability of this conclusion. In addition, IVW-based reverse-MR analysis revealed that OA did not increase the risk of hyperthyroidism (OR = 1.02, 95% CI = 0.97-1.08; P = 0.449). Hyperthyroidism is associated with an increased risk of OA, but the underlying pathological mechanism still needs to be clarified in future research.

Enhancing hepatoprotective action: oxyberberine amorphous solid dispersion system targeting TLR4.

Oxyberberine (OBB) is a significant natural compound, with excellent hepatoprotective properties. However, the poor water solubility of OBB hinders its release and absorption thus resulting in low bioavailability. To overcome these drawbacks of OBB, amorphous spray-dried powders (ASDs) of OBB were formulated. The dissolution, characterizations, and pharmacokinetics of OBB-ASDs formulation were investigated, and its hepatoprotective action was disquisitive in the D-GalN/LPS-induced acute liver injury (ALI) mouse model. The characterizations of OBB-ASDs indicated that the crystalline form of OBB active pharmaceutical ingredients (API) was changed into an amorphous form in OBB-ASDs. More importantly, OBB-ASDs showed a higher bioavailability than OBB API. In addition, OBB-ASDs treatment restored abnormal histopathological changes, improved liver functions, and relieved hepatic inflammatory mediators and oxidative stress in ALI mice. The spray drying techniques produced an amorphous form of OBB, which could significantly enhance the bioavailability and exhibit excellent hepatoprotective effects, indicating that the OBB-ASDs can exhibit further potential in hepatoprotective drug delivery systems. Our results provide guidance for improving the bioavailability and pharmacological activities of other compounds, especially insoluble natural compounds. Meanwhile, the successful development of OBB-ASDs could shed new light on the research process of poorly soluble medicine.

Recent advances on environmental behavior of Cu-based nanomaterials in soil-plant system: A review.

In recent years, copper-based nanomaterials (Cu-based NMs) have shown great potential in promoting agriculture development due to their special physicochemical characteristics. With the mass production and overuse of Cu-based NMs, there are potential effects on the soil-plant environment. Soil organisms, especially soil microorganisms, play a significant part in terrestrial or soil ecosystems; plants, as indirect organisms with soil-related Cu-based NMs, may affect human health through plant agricultural products. Understanding the accumulation and transformation of Cu-based NMs in soil-plant systems, as well as their ecotoxicological effects and potential mechanisms, is a prerequisite for the scientific assessment of environmental risks and safe application. Therefore, based on the current literature, this review: (i) introduces the accumulation and transformation behaviors of Cu-based NMs in soil and plant systems; (ii) focuses on the ecotoxicological effects of Cu-based NMs on a variety of organisms (microorganisms, invertebrates, and plants); (iii) reveals their corresponding toxicity mechanisms. It appears from studies hitherto made that both Cu-based NMs and released Cu2+ may be the main reasons for toxicity. When Cu-based NMs enter the soil-plant environment, their intrinsic physicochemical properties, along with various environmental factors, could also affect their transport, transformation, and biotoxicity. Therefore, we should push for intensifying the multi-approach research that focuses on the behaviors of Cu-based NMs in terrestrial exposure environments, and mitigates their toxicity to ensure the promotion of Cu-based NMs.

Inverse association of the systemic immune-inflammation index with serum anti-ageing protein Klotho levels in individuals with osteoarthritis: A cross-sectional study.

BACKGROUND: The association between the systemic immune-inflammation index (SII) and the serum soluble-Klotho concentration (pg/ml) in osteoarthritis (OA) patients is unknown. This study aimed to investigate the relationship between the SII and serum soluble-Klotho levels in OA patients. METHODS: All study data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (n = 1852 OA patients; age range = 40-79 years). The SII and serum Klotho measurement data are from the NHANES mobile examination centre. The SII values were divided into quartiles (Q1-4: 0.02-3.36, 3.36-4.78, 4.79-6.70, and 6.70-41.75). A multivariate linear regression model was constructed to evaluate the association between the SII and serum Klotho levels in OA patients; interaction tests were conducted to test the stability of the statistical results. RESULTS: Multivariate linear regression revealed a negative linear relationship between the SII and serum Klotho concentration in OA patients (ß = -6.05; 95% CI: -9.72, -2.39). Compared to Q1, Q4 was associated with lower serum Klotho concentrations (ß = -59.93; 95% CI: -96.57, -23.28). Compared with that of Q1, the ß value of Q2-Q4 showed a downwards trend as the SII increased (Ptrend <0.001). The stratified analysis results indicated that the SII had a greater sensitivity in predicting serum Klotho concentrations in OA patients aged 60-79 years (Pinteraction = 0.028). CONCLUSIONS: There was a significant negative linear correlation between the SII and serum Klotho concentration in OA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in OA patients. Klotho may be a potential anti-inflammatory drug for OA treatment.

Mitigation of inflammatory bowel disease-related osteoporosis by oxyberberine: Insights into the RANKL/NF-κB signaling pathway.

Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease.

Deciphering the molecular and clinical characteristics of TREM2, HCST, and TYROBP in cancer immunity: A comprehensive pan-cancer study.

Background: Hematopoietic cell signal transducer (HCST) and tyrosine kinase-binding protein (TYROBP) are triggering receptors expressed on myeloid cells 2 (TREM2), which are pivotal in the immune response to disease. Despite growing evidence underscoring the significance of TREM2, HCST, and TYROBP in certain forms of tumorigenesis, a comprehensive pan-cancer analysis of these proteins is lacking. Methods: Multiple databases were synthesized to investigate the relationship between TREM2, HCST, TYROBP, and various cancer types. These include prognosis, methylation, regulation by long non-coding RNAs and transcription factors, immune signatures, pathway activity, microsatellite instability (MSI), tumor mutational burden (TMB), single-cell transcriptome profiling, and drug sensitivity. Results: TREM2, HCST, and TYROBP displayed extensive somatic changes across numerous tumors, and their mRNA expression and methylation levels influenced patient outcomes across multiple cancer types. long non-coding RNA (lncRNA) -messenger RNA (mRNA) and TF-mRNA regulatory networks involving TREM2, HCST, and TYROBP were identified, with lncRNA MEG3 and the transcription factor SIP1 emerging as potential key regulators. Further immune analyses indicated that TREM2, HCST, and TYROBP play critical roles in immune-related pathways and macrophage differentiation, and may be significantly associated with TGF-ß and SMAD9. Furthermore, the expression of TREM2, HCST, and TYROBP correlated with the immunotherapy markers TMB and MSI, and influenced sensitivity to immune-targeted drugs, thereby indicating their potential as predictors of immunotherapy outcomes. Conclusion: This study offers valuable insights into the roles of TREM2, HCST, and TYROBP in tumor immunotherapy, suggesting their potential as prognostic markers and therapeutic targets for various cancers.

Associations of recurrent lumbar disc herniation after percutaneous endoscopic lumbar discectomy with age, body mass index, modic change, disc degeneration and sacral slope: A quantitative review.

Recurrent lumbar disc herniation (rLDH) seriously affects the quality of life of patients and increases the medical burden. The purpose of the present study was to determine the risk factors for rLDH after percutaneous endoscopic lumbar discectomy (PELD). The PubMed, Cochrane Library and Embase databases were searched for studies on the factors associated with rLDH after PELD. The databases were searched from inception to March 30, 2023. The combined effects of categorical variables and continuous variables were measured using odds ratios (ORs) and weighted mean differences (WMDs), respectively, and their corresponding 95% confidence intervals (CIs) were calculated. RevMan 5.3 software was used for data analysis. A total of 9 case-control studies were included in this meta-analysis, comprising 5,446 patients. This study explored a total of 18 potential risk factors for rLDH after PELD; ultimately, 5 factors were associated with the risk of rLDH. Meta-analysis showed that older age (WMD=6.49, 95% CI: 2.52 to 10.46), greater body mass index (WMD=1.16, 95% CI: 0.69 to 1.62), modic change (OR=2.48, 95% CI: 1.54 to 3.99), Pfirrmann grade ≥4 (OR=2.84, 95% CI: 1.3 to 6.16) and greater sacral slope angle (WMD=3.48, 95% CI: 0.53 to 6.42) were risk factors for rLDH after PELD. The risk factors identified in the present study may enable clinicians to identify high-risk populations early and to select appropriate surgical procedures to reduce the risk of rLDH. Perioperative interventions targeting the modifiable factors identified in this study may be beneficial for reducing the risk of rLDH.

Current progress on manganese in constructed wetlands: Bibliometrics, effects on wastewater treatment, and plant uptake.

Constructed wetlands (CWs) are a pollutant treatment design inspired by natural wetlands and are widely utilized for the removal of common pollutants. The research focus lies in the circulation of manganese (Mn) in the environment to enhance pollutant removal within CWs. This paper provides a comprehensive review of recent advancements in understanding the role and effects of Mn in chemical weapons, based on literature retrieval from 2002 to 2021. Ecological risk assessment and heavy metals within CWs emerge as current areas of research interest. Mn sources within CWs primarily include natural deposition, heavy metal wastewater, and intentional addition. The cycling between Mn(II) and Mn(IV) facilitates enhanced wastewater treatment within CWs. Moreover, employing a Mn matrix proves effective in reducing ammonia nitrogen wastewater, organic pollutants, as well as heavy metals such as Cd and Pb, thereby addressing complex pollution challenges practically. To comprehensively analyze influencing factors on the system's performance, both internal factors (biological species, design parameters, pH levels, etc.) and external factors (seasonal climate variations, precipitation patterns, ultraviolet radiation exposure, etc.) were discussed. Among these factors, microorganisms, pollutants, and temperature are the most important influencing factors, which emphasizes the importance of these factors for wetland operation. Lastly, this paper delves into plant absorption of Mn along with coping strategies employed by plants when faced with Mn poisoning or deficiency scenarios. When utilizing Mn for the regulation of constructed wetlands, it is crucial to consider the tolerance levels of associated plant species. Furthermore, the study predicts future research hotspots encompass high-efficiency catalysis techniques, matrix-filling approaches, and preparation of resource utilization methods involving Mn nanomaterials.

Transcriptomic analyses and machine-learning methods reveal dysregulated key genes and potential pathogenesis in human osteoarthritic cartilage.

Aims: This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods: Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results: A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion: The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets.

Interplay of Systemic Immune-Inflammation Index and Serum Klotho Levels: Unveiling a New Dimension in Rheumatoid Arthritis Pathology.

Aim: The association between the systemic immune-inflammation index (SII) and serum Klotho concentrations (pg/ml) in patients with rheumatoid arthritis (RA) has not been elucidated. The purpose of this study was to clarify the relationship between the SII and serum Klotho concentrations in RA patients. Methods: All data come from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which included 982 RA patients (age range: 40 to 79 years). The measurement data of the SII and serum Klotho are all from the NHANES mobile examination centre. We constructed a multivariate linear regression model to evaluate the association between the SII and serum Klotho levels in RA patients and conducted a subgroup analysis to test the stability of the statistical results. Results: Multivariate linear regression results indicated a negative linear relationship between the SII and serum Klotho concentrations in RA patients (ß = -6.33, 95% CI [confidence interval]: -10.15 to -2.53). Compared to the quartile 1 group, the quartile 4 group was associated with significantly lower (P<0.001) serum Klotho concentrations (ß = -120.93, 95% CI: -174.84 to -67.02). Compared with the quartile 1 group, with the increase in the SII, the ß value showed a decreasing trend (P trend < 0.001). The subgroup analysis showed that none of the covariates affected the stability of these results (all P for interaction ≥ 0.05). Conclusion: There is a significant negative linear association between the SII and serum Klotho concentrations in RA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in RA patients, and Klotho may be a potential anti-inflammatory target for RA treatment.

Liuwei Dihuang Pills Enhance Osteogenic Differentiation in MC3T3-E1 Cells through the Activation of the Wnt/ß-Catenin Signaling Pathway.

OBJECTIVE: The therapeutic efficacy and molecular mechanisms of traditional Chinese medicines (TCMs), such as Liuwei Dihuang pills (LWDH pills), in treating osteoporosis (OP) remain an area of active research and interest in modern medicine. This study investigated the mechanistic underpinnings of LWDH pills in the treatment of OP based on network pharmacology, bioinformatics, and in vitro experiments. METHODS: The active ingredients and targets of LWDH pills were retrieved through the TCMSP database. OP-related targets were identified using the CTD, GeneCards, and DisGeNET databases. The STRING platform was employed to construct a protein-protein interaction (PPI) network, and core targets for LWDH pills in treating OP were identified. The GO functional and KEGG pathway enrichment analyses for potential targets were performed using the R package "clusterProfiler". A "drug-target" network diagram was created using Cytoscape 3.7.1 software. The viability of MC3T3-E1 cells was evaluated using the CCK-8 method after treatment with various concentrations (1.25%, 2.5%, 5%, and 10%) of LWDH pill-medicated serum for 24, 48, and 72 h. Following a 48 h treatment of MC3T3-E1 cells with LWDH pill-medicated serum, the protein levels of collagen Ⅰ, RUNX2, Wnt3, and ß-catenin were quantified using the Western blot analysis, and the activity of alkaline phosphatase (ALP) was measured. RESULTS: A total of 197 putative targets for LWDH pills for OP treatment were pinpointed, from which 20 core targets were singled out, including TP53, JUN, TNF, CTNNB1 (ß-catenin), and GSK3B. The putative targets were predominantly involved in signaling pathways such as the Wnt signaling pathway, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. The intervention with LWDH pill-medicated serum for 24, 48, and 72 h did not result in any notable alterations in the cell viability of MC3T3-E1 cells relative to the control group (all p > 0.05). Significant upregulation in protein levels of collagen Ⅰ, RUNX2, Wnt3, and ß-catenin in MC3T3-E1 cells was observed in response to the treatment with 2.5%, 5%, and 10% of LWDH pill-medicated serum in comparison to that with the 10% rabbit serum group (all p < 0.05). Furthermore, the intervention with LWDH pill-medicated serum resulted in the formation of red calcified nodules in MC3T3-E1 cells, as indicated by ARS staining. CONCLUSIONS: LWDH pills may upregulate the Wnt/ß-catenin signaling pathway to elevate the expression of osteogenic differentiation proteins, including collagen Ⅰ and RUNX2, and to increase the ALP activity in MC3T3-E1 cells for the treatment of OP.

Urinary podocyte stress marker as a prognostic indicator for diabetic kidney disease.

BACKGROUND: Diabetic kidney diseases (DKD) is a the most common cause of end-stage kidney disease (ESKD) around the world. Previous studies suggest that urinary podocyte stress biomarker, e.g. podocin:nephrin mRNA ratio, is a surrogate marker of podocyte injury in non-diabetic kidney diseases. METHOD: We studied 118 patients with biopsy-proved DKD and 13 non-diabetic controls. Their urinary mRNA levels of nephrin, podocin, and aquaporin-2 (AQP2) were quantified. Renal events, defined as death, dialysis, or 40% reduction in glomerular filtration rate, were determined at 12 months. RESULTS: Urinary podocin:nephrin mRNA ratio of DKD was significantly higher than the control group (p = 0.0019), while urinary nephrin:AQP2 or podocin:AQP2 ratios were not different between groups. In DKD, urinary podocin:nephrin mRNA ratio correlated with the severity of tubulointerstitial fibrosis (r = 0.254, p = 0.006). and was associated with the renal event-free survival in 12 months (unadjusted hazard ratio [HR], 1.523; 95% confidence interval [CI] 1.157-2.006; p = 0.003). After adjusting for clinical and pathological factors, urinary podocin:nephrin mRNA ratio have a trend to predict renal event-free survival (adjusted HR, 1.327; 95%CI 0.980-1.797; p = 0.067), but the result did not reach statistical significance. CONCLUSION: Urinary podocin:nephrin mRNA ratio has a marginal prognostic value in biopsy-proven DKD. Further validation is required for DKD patients without kidney biopsy.

Guidelines for the Diagnosis and Treatment of Rotator Cuff Tear with Integrated Traditional Chinese and Western Medicine.

Rotator cuff tear is one of the common diseases among middle-aged and elderly people, which has a great impact on patients' physical and mental health and quality of life. The integrative medicine based on traditional Chinese medicine has certain characteristics and advantages in the diagnosis and treatment of Rotator cuff tear. Chinese medicine, which mainly focus on plant-based natural products, has a relatively stable and reliable curative effect. It is of great significance to formulate the combined diagnosis and treatment plan for Rotator cuff tear based on evidence-based medicine, which can help to make the clinical diagnosis and treatment techniques of Chinese and Western medicine more scientific and standardized, and achieve better therapeutic effects. This guideline standardizes the diagnosis and treatment process of Rotator cuff tear from the aspects of range, terminology and definition, diagnosis, TCM syndrome differentiation, treatment, functional exercise, prevention and care, etc. It can better provide clinicians with diagnosis and treatment strategies and suggestions. This guideline adapts well to clinical practice and is both safe and effective.

Intravenous Tranexamic Acid Significantly Improved Visualization and Shortened the Operation Time in Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis of Level I and II Studies.

PURPOSE: To further clarify the role of tranexamic acid (TXA) in arthroscopic rotator cuff repair (ARCR), especially visual field clarity and operation time. METHODS: We searched the PubMed, Cochrane Library, and Embase databases to find prospective randomized controlled clinical trials (RCTs) examining the use of TXA in ARCR. All included RCTs were evaluated for methodological quality using the Cochrane Collaboration's risk of bias tool. We used Review Manager 5.3 for meta-analysis and calculated the weighted mean difference (WMD) and 95% confidence interval (CI) of the related outcome indicators. The GRADE system was used to evaluate the strength of the clinical evidence provided by the included studies. RESULTS: Six RCTs (3 Level I, 3 Level II) from four countries or regions were included in this study: 2 studies used intra-articular (IA) TXA, and 4 studies used intravenous TXA. A total of 451 patients underwent ARCR, including 227 patients in the TXA group and 224 patients in the non-TXA group. In 2 RCTs evaluating good visualization, intravenous TXA achieved a better surgical field of view in ARCR compared to the control group (P =.036; P = .045). Meta-analysis showed that compared with non-TXA, intravenous TXA shortened the operation time (WMD = -12.87 min, 95% CI: -18.81 to -6.93). These two RCTs did not reveal a statistically significant difference in the impact of intravenous TXA and non-TXA on mean arterial pressure (MAP) (P = .306; P = .549). Compared with epinephrine (EPN), IA TXA had no significant effects on improving the visual field clarity under arthroscopy, shortening the operation time or reducing the total amount of irrigation fluid (P > .05). Compared with saline irrigation, IA TXA improved the surgical field of vision and shortened the operation time (P < .001). No adverse events were reported for either intravenous TXA or IA TXA. CONCLUSIONS: Intravenous TXA can shorten the operation time of ARCR, and the conclusions of existing RCTs suggest that intravenous TXA can improve visual field clarity during ARCR, thus supporting the application of intravenous TXA in ARCR. Compared with EPN, IA TXA was not better at improving the visual field clarity under arthroscopy and shortening the operation time, but it was better than saline irrigation. LEVEL OF EVIDENCE: Level II, systematic review and meta-analysis of Level I and II studies.

Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenolic compound extracted from turmeric (Curcuma longa L.), is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis. Clinical and experimental studies show that curcuminoid formulations have considerable clinical application value in the treatment of knee osteoarthritis (KOA). AIM OF THE STUDY: To evaluate the efficacy and safety of curcumin, both alone and in combination with other drugs, in KOA treatment through a Bayesian network meta-analysis (NMA). METHODS: We searched PubMed, Embase and Cochrane Library for randomized controlled trials of curcumin for KOA treatment. The time range of the search was from the establishment of each database to April 26, 2023. The NMAs of outcome indicators were all performed using a random-effects model. NMAs were calculated and graphed in R using MetaInsight and Stata 140 software. Measurement data were represented by the mean difference (MD), while count data were represented by the odds ratio (OR); the 95% confidence interval (CI) of each effect size was also calculated. RESULTS: This study included 23 studies from 7 countries, including 2175 KOA patients and 6 interventions. The NMA results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score (MD = -1.63, 95% CI: -2.91 to -0.45) and total WOMAC score (MD = -18.85, 95% CI: -29.53 to -8.76). Compared with placebo, curcumin (OR = 0.17, 95% CI: 0.08 to 0.36), curcumin + NSAIDs (OR = 0.01, 95% CI: 0.00 to 0.13) and NSAIDs (OR = 0.11, 95% CI: 0.02 to 0.47) reduced the use of rescue medication. Compared with NSAIDs, curcumin (OR = 0.51, 95% CI: 0.25 to 0.94) and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) had a reduced incidence of adverse reactions. The surface under the cumulative ranking curve results indicated that curcumin monotherapy, curcumin + chondroprotective agents, and curcumin + NSAIDs have good clinical value in KOA treatment. CONCLUSIONS: Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in KOA treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.

J-shaped association of serum uric acid concentrations with all-cause mortality in individuals with osteoarthritis: A prospective cohort study.

OBJECTIVE: The purpose of this study was to explore the relationship between serum uric acid (SUA) concentrations and all-cause mortality in individuals with osteoarthritis (OA). METHODS: All participant data were retrieved from the National Health and Nutrition Examination Survey database. A total of 4671 participants (age range: 20 to 85 years old), including 2988 females and 1683 males, were included in this study. The determination of death outcome was based on the National Death Index (up to December 31, 2019). We explored the nonlinear relationship between SUA concentrations and all-cause mortality in OA patients by establishing a Cox proportional risk model and a two-segment Cox proportional risk model and ran an interaction test to identify the high-risk population for all-cause mortality. RESULTS: During 30,645 person-years of follow-up, the number of all-cause deaths for females and males was 736 and 516, respectively. After multivariate adjustment, we found a nonlinear relationship between SUA concentrations and all-cause mortality in both females and males with OA. In addition, we found a J-shaped relationship between SUA concentrations and all-cause mortality. The SUA concentration thresholds for all-cause mortality of females and males were stable at 5.6mg/dl and 6.2mg/dl, respectively. Compared with SUA concentrations below the inflection point, the all-cause mortality risk at higher SUA concentrations in females and males with OA increased by 20% (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 1.1 to 1.2) and 25% (HR: 1.2, 95% CI: 1.12 to 1.39), respectively. CONCLUSIONS: There is a nonlinear relationship between SUA concentrations and all-cause mortality in the American OA population (J-shaped association). The all-cause mortality thresholds for SUA concentrations in females and males are 5.6mg/dl and 6.2mg/dl, respectively.

Higher systemic immune-inflammation index is associated with sarcopenia in individuals aged 18-59 years: a population-based study.

The association between the systemic immune-inflammation index (SII) and the risk of sarcopenia has not yet been revealed. The purpose of this study was to investigate the relationship between the SII and sarcopenia in individuals aged 18-59 years. All data for this study are from the National Health and Nutrition Examination Survey (NHANES) database, including 7258 participants (age range: 18-59 years). We divided SII values by quartiles (quartiles 1-4: 0.3-3.1, 3.2-4.4, 4.4-6.2, and 6.2-58.5). We constructed a multivariate logistic regression model to assess the association between the SII and the risk of sarcopenia, and an interaction test was run to test the stability of the model and identify high-risk individuals with sarcopenia. Compared to nonsarcopenia participants, sarcopenia patients had a significantly higher SII value (weighted average: 6.65 vs. 5.16) (P = 0.002). Multivariate logistic regression results showed a positive linear relationship between the SII and sarcopenia (OR [odds ratio] = 1.12, 95% CI [confidence interval] 1.03-1.21). Compared to the quartile 1 group, the quartile 4 group was associated with a higher risk of sarcopenia (OR = 3.94, 95% CI 1.42-10.94). Compared with the quartile 1 group, the OR value of the quartile 2 to quartile 4 groups showed an upwards trend (Ptrend < 0.001) as the level of SII increased. Subgroup analysis also indicate that the correlation between higher SII values and the risk of sarcopenia was stable. There was a significant positive linear relationship between SII and sarcopenia, indicating that higher SII values can increase the risk of sarcopenia in individuals aged 18-59 in the United States. The findings of this study will be beneficial in promoting the use of SII alone or in combination with other tools for the risk screening of sarcopenia in communities or large populations.