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.

Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has great advantages in the treatment of unicompartmental knee osteoarthritis, but its revision rate is higher than that of total knee arthroplasty. AIM: To summarize and analyse the causes of revision after UKA. METHODS: This is a retrospective case series study in which the reasons for the first revision after UKA are summarized. We analysed the clinical symptoms, medical histories, laboratory test results, imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA. RESULTS: A total of 13 patients, including 3 males and 10 females, underwent revision surgery after UKA. The average age of the included patients was 67.62 years. The prosthesis was used for 3 d to 72 months. The main reasons for revision after UKA were improper suturing of the surgical opening (1 patient), osteophytes (2 patients), intra-articular loose bodies (2 patients), tibial prosthesis loosening (2 patients), rheumatoid arthritis (1 patient), gasket dislocation (3 patients), anterior cruciate ligament injury (1 patient), and medial collateral ligament injury with residual bone cement (1 patient). CONCLUSION: The causes of primary revision after UKA were gasket dislocation, osteophytes, intra-articular loose bodies and tibial prosthesis loosening. Avoidance of these factors may greatly reduce the rate of revision after UKA, improve patient satisfaction and reduce medical burden.

A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects.

PURPOSE: This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects. METHODS: Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct three-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean and standard deviation and compared using independent sample t-tests. RESULTS: In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment. CONCLUSION: Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

Recent advance in sesame allergens: Influence of food processing and their detection methods.

Sesame (Sesamum indicum L.) is a valuable oilseed crop with numerous nutritional benefits containing a diverse range of bioactive compounds. However, sesame is also considered an allergenic food that triggers various mild to severe adverse reactions (e.g., anaphylaxis). Strict dietary avoidance of sesame components is the best option to protect the sensitized consumers. Sesame or sesame-derived foods are always consumed after certain food processing operations, which would cause a considerable impact on the structure of sesame proteins, changing their sensitization capacity and detectability. In the review, the molecular structure properties, and immunological characteristics of the sesame allergens were described. Meanwhile, the influence of food processing techniques on sesame proteins and the relevant detection techniques used for the sesame allergens quantification are also emphasized critically. Hopefully, this review could provide valuable insight into the development and management for the new "Big Eight" sesame allergen in food industry.

A rapid identification method for soft tissue markers of dentofacial deformities based on heatmap regression.

OBJECTIVE: The purpose of this study was to construct a facial deformity dataset and a network model based on heatmap regression for the recognition of facial soft tissue landmarks to provide a basis for clinicians to perform cephalometric analysis of soft tissue. MATERIALS AND METHODS: A 34-point face marker detection model, the Back High-Resolution Network (BHR-Net), was constructed based on the heatmap regression algorithm, and a custom dataset of 1780 facial detection images for orthognathic surgery was collected. The mean normalized error (MNE) and 10% failure rate (FR10%) were used to evaluate the performance of BHR-Net, and a test set of 50 patients was used to verify the accuracy of the landmarks and their measurement indicators. The test results were subsequently validated in 30 patients. RESULTS: Both the MNE and FR10% of BHR-Net were optimal compared with other models. In the test set (50 patients), the accuracy of the markers excluding the nose root was 86%, and the accuracy of the remaining markers reached 94%. In the model validation (30 patients), using the markers detected by BHR-Net, the diagnostic accuracy of doctors was 100% for Class II and III deformities, 100% for the oral angle plane, and 70% for maxillofacial asymmetric deformities. CONCLUSIONS: BHR-Net, a network model based on heatmap regression, can be used to effectively identify landmarks in maxillofacial multipose images, providing a reliable way for clinicians to perform cephalometric measurements of soft tissue objectively and quickly.

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.

A comprehensive review on mango allergy: Clinical relevance, causative allergens, cross-reactivity, influence of processing techniques, and management strategies.

Mangoes (Mangifera indica) are widely prized for their abundant nutritional content and variety of beneficial bioactive compounds and are popularly utilized in various foods, pharmaceuticals, and cosmetics industries. However, it is important to note that certain proteins present in mango can trigger various allergic reactions, ranging from mild oral allergy syndrome to severe life-threatening anaphylaxis. The immunoglobulin E-mediated hypersensitivity of mango is mainly associated with three major allergenic proteins: Man i 1 (class IV chitinase), Man i 2 (pathogenesis-related-10 protein; Bet v 1-related protein), and Man i 4 (profilin). Food processing techniques can significantly affect the structure of mango allergens, reducing their potential to cause allergies. However, it is worth mentioning that complete elimination of mango allergen immunoreactivity has not been achieved. The protection of individuals sensitized to mango should be carefully managed through an avoidance diet, immediate medical care, and long-term oral immunotherapy. This review covers various aspects related to mango allergy, including prevalence, pathogenesis, symptoms, and diagnosis. Furthermore, the characterization of mango allergens and their potential cross-reactivity with other fruits, vegetables, plant pollen, and seeds were discussed. The review also highlights the effects of food processing on mango and emphasizes the available strategies for managing mango allergy.

The impact of alloying element Cu on corrosion and biofilms of 316L stainless steel exposed to seawater.

Copper-containing stainless steel (SS) has been reported to mitigate biofilms in industrial and clinical environments. However, the impact of copper released from copper-containing SS in natural seawater on biofilms and corrosion is still unclear. In this study, three kinds of 316L SS were immersed in natural seawater for 6 months, and the pitting depth decreased in the order: 316L-Cu SS (annealed) > 316L SS > 316L-Cu SS (aged). The biofilm thickness and number of sessile cells on the surface of 316L-Cu SS (annealed) and 316L SS were similar but notably greater than those of 316L-Cu SS (aged). Furthermore, the results of the community analysis indicated that the addition of copper in 316L-Cu SS (aged) reduced the diversity and richness of the microbial community, resulting in a significant reduction in the number of genera constituting the biofilms. Copper ions exhibit a broad-spectrum bactericidal effect, effectively reducing the abundance of dominant populations and microbial genera in the biofilms, thereby mitigating pitting corrosion induced by microorganisms. In addition, the PCoA scatter plot showed that time also played an important role in the regulation of microbial community structure.

Research Progress in Single-herb Chinese Medicine and Compound Medicine for Knee Osteoarthritis.

Due to an increase in the aging population, osteoarthritis (OA), especially knee osteoarthritis (KOA), has increasingly become one of the diseases affecting the quality of life of the elderly. As the pathogenesis of KOA is still unclear, Western medicine treatment lacks specificity, and surgical treatment is difficult to cover all patients. Therefore, in recent years, traditional Chinese medicine (TCM) for the conservative treatment of KOA has received increasing attention. The advantages of TCM are clear， such as relief of symptoms, fewer adverse reactions, and wider applicability to patients. This paper mainly discusses the research progress in single-herb TCM and TCM compounds for KOA, aiming to demonstrate the effectiveness of TCM in the treatment of KOA. It also provides ideas for future research on the treatment of KOA by TCM and the pathogenesis of knee osteoarthritis.

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.

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.

Combatting cyanobacteria: unraveling the potency of 316L-Cu stainless steel in inhibiting Microcystis aeruginosa growth.

Harmful algal blooms, particularly those of Microcystis aeruginosa, present significant ecological and health risks. To address this issue, this study utilized a custom static algal growth assessment apparatus to investigate the anti-algal performance of a copper-alloyed 316L stainless steel (SS), named 316L-Cu SS. This material was compared with traditional 316L SS, which is widely utilized in freshwater systems for its corrosion resistance. Algal growth dynamics were monitored through optical density (OD) and chlorophyll A concentration measurements. Notably, 316L-Cu SS exhibited superior inhibitory effects on Microcystis aeruginosa growth compared to 316L SS and control groups. Inductively coupled plasma mass spectrometry (ICP-MS) confirmed that the copper ion release from 316L-Cu SS played a critical role in this algal suppression, which interfered with photosynthesis, induced oxidative stress, and damaged algal cell membranes. In contrast, other metal ions (Ni, Cr, Fe) had a negligible impact on algal growth. The study highlights 316L-Cu SS as a promising material for mitigating harmful algal blooms, thereby offering potential benefits for both aquatic ecosystem conservation and public health protection.

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.

Discovery of (S)-3-(4-(benzyloxy)phenyl)-2-(2-phenoxyacetamido)propanoic acid derivatives as a new class of GPR34 antagonists.

GPR34 is a rhodopsin-like class G protein-coupled receptor (GPCR) that is involved in the development and progression of several diseases. Despite its importance, effective targeting strategies are lacking. We herein report a series of (S)-3-(4-(benzyloxy)phenyl)-2-(2-phenoxyacetamido)propanoic acid derivatives as a new class of GPR34 antagonists. Structure-activity relationship (SAR) studies led to the identification of the most potent compound, 5e, which displayed an IC50 value of 0.680 µM in the GloSensor cAMP assay and 0.059 µM in the Tango assay. 5e demonstrated low cytotoxicity and high selectivity in vitro, and it was able to dose-dependently inhibit Lysophosphatidylserine-induced ERK1/2 phosphorylation in CHO cells expressing GPR34. Furthermore, 5e displayed excellent efficacy in a mouse model of neuropathic pain without any apparent signs of toxicity. Collectively, this study has identified a promising compound, which shows great potential in the development of potent antagonists with a new chemical scaffold targeting GPR34.

Development of a fluorescent multiplexed lateral flow immunoassay for the simultaneous detection of crustacean allergen tropomyosin, sarcoplasmic calcium binding protein and egg allergen ovalbumin in different matrices and commercial foods.

A quantum dot (QD) based multiplexed lateral flow immunoassay (xLFIA) for the simultaneous detection of egg allergen ovalbumin, crustacean allergen tropomyosin (TM) and sarcoplasmic calcium binding protein (SCP) was developed in this study. QD-labeled rabbit anti-ovalbumin, SCP and TM antibodies were applied as fluorescent detection probes. The chromatography system was optimized to reduce the mutual interference of different test lines. Visual and instrumental detection limits of the xLFIA were 0.1 and 0.05 µg/mL for SCP, both 0.05 µg/mL for ovalbumin and both 0.5 µg/mL for TM. As low as 0.10 % crab powder, 0.01 % egg white powder and 0.05 % shrimp powder could be detected in all three model foods using xLFIA. Besides, the xLFIA detection results of 23 of 28 commercial foods were consistent with ingredient labels. These findings indicate that the developed xLFIA is a practical tool for point-of-care detection of egg and crustacean allergens in processed and commercial foods.

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.

Effectiveness of Chinese Herbal Medicine in Postoperative Fatigue Syndrome Following Total Joint Arthroplasty or Hip Fracture Surgery: Evidence from Randomized Controlled Trials.

BACKGROUND: There is no high-quality, evidence-based protocol for the treatment of postoperative fatigue syndrome (POFS) after total joint arthroplasty (TJA) or fracture surgery with Chinese herbal medicine (CHM). PURPOSE: The purpose of this study was to explore the efficacy of CHM in the treatment of POFS after TJA or hip fracture surgery (HFS). METHODS: We searched six databases to obtain randomized controlled trials (RCTs) of CHM for the treatment of POFS after TJA or HFS. The retrieval time limit was from the establishment of each database to August, 2022. According to the Cochrane Handbook for Systematic Reviews version 5.1, we used RevMan 5.3 to evaluate the quality of the studies. Stata 14.0 software was used to merge and analyze the data. The weighted mean difference (WMD) was the effect estimate for statistical analysis. We also performed subgroup analyses according to different types of surgeries. RESULTS: A total of 11 RCTs were included in this study, comprising 430 cases in the CHM group and 432 cases in the control group (CG). The meta-analysis results showed that there was no significant difference in the Brief Profile of Mood States (BPOMS) score (WMD=0.08, 95% confidence interval (CI): -0.29 to 0.45, P=0.688), Christensen Fatigue scale (CHFS) score (WMD = 0.15, 95% CI: -0.09 to 0.39, P=0.214) or Identity-Consequence Fatigue Scale (ICFS) score (WMD=-0.40, 95% CI: -1.84 to 1.05, P=0.589) between the CHM group and the CG on the first postoperative day. The use of CHM significantly reduced the BPOMS score (WMD=-0.85 and WMD=-3.01, respectively), CHFS score (WMD=-1.01 and WMD= -1.45, respectively), and ICFS score (WMD=-3.51 and WMD=-5.26) on postoperative days 3 and 7. Compared with the CG, the CHM group had significantly increased serum transferrin and IgG levels on postoperative days 3 and 7. The subgroup analysis results suggested that the application of CHM in HFS patients improved fatigue symptoms on postoperative days 3 and 7, while the application of CHM to treat POFS in TJA patients had great inconsistency in the evaluation of different indicators. CONCLUSION: The application of CHM improved the fatigue status of POFS patients after TJA or HFS and increased the levels of transferrin and IgG in serum, which is conducive to promoting the postoperative rehabilitation process of patients. The subgroup analysis results showed that the application of CHM to intervene in POFS in HFS patients had obvious benefits.

A Stable Irinotecan Liposome with Enhanced Antitumor Activity in a Range of Tumor Models.

PURPOSE: This study aimed to prepare a stable irinotecan liposome (CPT-11 liposome) and evaluate its antitumor efficacy in a range of tumor models. METHODS: CPT-11 liposome was prepared with a Z-average particle size of 110 ~ 120 nm and high entrapment efficiency (> 95%) and had a good stability within 18 months. Then the antitumor efficacy was studied in human colon (Ls-174t), gastric (NCI-N87), pancreatic (BxPC-3) and small cell lung (NCI-H526) cancer xenograft models. The toxicity of high-dose CPT-11 liposome was also evaluated in Beagle dogs. RESULTS: The results showed that the anti-tumor effects of CPT-11 liposome were markedly superior (at least 10 times higher) to those of the CPT-11 injection group in all four xenograft models. The tissue distribution test in the Ls-174t model further demonstrated that the CPT-11 liposome could alter the plasma and tissue distribution of CPT-11, increase the exposure level of its active metabolite SN-38 in tumor, and ultimately improve antitumor efficiency. Meanwhile, CPT-11 liposome showed a much less toxicity than CPT-11 injection in beagle dogs. CONCLUSIONS: Overall, the CPT-11 liposome may be developed as a new clinical alternative for the cancer patients.