Cryo-EM structures of human GPR34 enable the identification of selective antagonists.

GPR34 is a functional G-protein-coupled receptor of Lysophosphatidylserine (LysoPS), and has pathogenic roles in numerous diseases, yet remains poorly targeted. We herein report a cryo-electron microscopy (cryo-EM) structure of GPR34 bound with LysoPS (18:1) and Gi protein, revealing a unique ligand recognition mode with the negatively charged head group of LysoPS occupying a polar cavity formed by TM3, 6 and 7, and the hydrophobic tail of LysoPS residing in a lateral open hydrophobic groove formed by TM3-5. Virtual screening and subsequent structural optimization led to the identification of a highly potent and selective antagonist (YL-365). Design of fusion proteins allowed successful determination of the challenging cryo-EM structure of the inactive GPR34 complexed with YL-365, which revealed the competitive binding of YL-365 in a portion of the orthosteric binding pocket of GPR34 and the antagonist-binding-induced allostery in the receptor, implicating the inhibition mechanism of YL-365. Moreover, YL-365 displayed excellent activity in a neuropathic pain model without obvious toxicity. Collectively, this study offers mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, and provides proof of concept that targeting GPR34 represents a promising strategy for disease treatment.

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.

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.

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.

A comprehensive review on novel synthetic foods: Potential risk factors, detection strategies, and processing technologies.

Nowadays, the food industry is facing challenges due to the simultaneous rise in global warming, population, and food consumption. As the integration of synthetic biology and food science, novel synthetic foods have obtained high attention to address these issues. However, these novel foods may cause potential risks related to human health. Four types of novel synthetic foods, including plant-based foods, cultured meat, fermented foods, and microalgae-based foods, were reviewed in the study. The original food sources, consumer acceptance, advantages and disadvantages of these foods were discussed. Furthermore, potential risk factors, such as nutritional, biological, and chemical risk factors, associated with these foods were described and analyzed. Additionally, the current detection methods (e.g., enzyme-linked immunosorbent assay, biosensors, chromatography, polymerase chain reaction, isothermal amplification, and microfluidic technology) and processing technologies (e.g., microwave treatment, ohmic heating, steam explosion, high hydrostatic pressure, ultrasound, cold plasma, and supercritical carbon dioxide) were reviewed and discussed critically. Nonetheless, it is crucial to continue innovating and developing new detection and processing technologies to effectively evaluate these novel synthetic foods and ensure their safety. Finally, approaches to enhance the quality of these foods were briefly presented. It will provide insights into the development and management of novel synthetic foods for food industry.

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.

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.

Pharmacological Interventions for Glucocorticoid-Induced Osteoporosis: An Umbrella Review.

There is still a lack of high-quality evidence-based studies on the efficacy of drug treatment for glucocorticoid-induced osteoporosis (GIOP). The purpose of this umbrella review is to comprehensively evaluate the existing evidence to determine the efficacy and safety of pharmacological interventions for GIOP. We searched PubMed, Embase, and the Cochrane Library for systematic reviews and/or meta-analyses (SRs) of randomized controlled trials (RCTs) aimed at evaluating drug therapy for GIOP. Both the methodological quality and the strength of recommendation of the endpoints included in the SRs were evaluated by using the AMSTAR-2 tool and GRADE system, respectively. Six SRs involving 7225 GIOP patients in 59 RCTs were included in this umbrella review. The results of the methodological quality evaluation showed that 2 high-quality, 2 low-quality and 2 critically low-quality SRs were included. The GRADE evaluation results showed that the quality of evidence and the strength of recommendation of 46 outcome indicators were evaluated in the umbrella review; there were 3 with high-level evidence, 20 with moderate-level evidence, 15 with low-level evidence, and 8 with very low-level evidence. Moderate- to high-level evidence suggests that teriparatide, bisphosphonates, and denosumab can improve the bone mineral density in patients with GIOP. The findings of this umbrella review can enable patients and clinical healthcare professionals to choose the best drug prescription.

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.

Identification of miR-1-3p, miR-143-3p and miR-145-5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation.

Gleason Score (GS) 3 + 4 prostate cancer (PCa) is heterogeneous in clinical course and molecular features. Risk stratification of indolent and aggressive PCa with GS 3 + 4 is critical, especially those with bone metastasis (BM) potential. Microarray-based microRNA(miRNA) profiling with eight PCa cases with or without BM was used to screen the candidate miRNAs associated with BM. Transwell and MTS assays were used to characterize the function of miRNAs and target gene LASP1. RT-qPCR and immunohistochemistry assays were utilized to illustrate the clinical significance of miRNAs and target gene in a cohort of 309 Chinese PCa cases. In the current study, we identified that miR-1-3p, miR-143-3p and miR-145-5p are associated with BM of GS 3 + 4 PCa. Through functional experiments, we show that miR-1-3p/143-3p/145-5p promotes proliferation and migration of PCa in vitro. LASP1 was predicted as the common target of these three miRNAs which was further confirmed by a luciferase assay. Overexpression of LASP1 was correlated with higher GS, higher pathological stage, and the presence of metastasis by immunohistochemistry. siRNA knockdown of LASP1 significantly suppressed proliferation and migration, whereas overexpression of LASP1 promoted it. Bioinformatics analysis revealed the involvement of Wnt signaling pathway in LASP1 mediated function. LASP1 may activate Wnt signaling by interacting with ß-catenin. In all, we suggest that miR-1-3p/143-3p/145-5p are associated with BM of Gleason 3 + 4 PCa. LASP1 is the common target of these miRNAs and may active Wnt signaling by interacting with ß-catenin.

Preparation of Conotoxin-Encapsulated Chitosan Nanoparticles and Evaluation of Their Skin Permeability.

µ-Conotoxin CnIIIC (conotoxin, CTX)-loaded chitosan nanoparticles (CTX-NPs) were prepared using the ionic cross-linking method. The CTX-NPs were spherical and well with a polydispersity index of 0.292 ± 0.039, drug loading efficiency of 25.9 ± 1.2%, and encapsulation efficiency of 95.6 ± 1.3%. In vitro release studies showed that the release behavior of CTX-NPs in a pH 5.0 acetate buffer followed zero-order kinetics. In vitro transdermal experiments using Franz diffusion cells mounted with mouse abdominal skin demonstrated that the cumulative intradermal deposition amount of CTX per unit area in 8 h (D8) and permeability coefficient (Pf) of CTX loaded on CTX-NPs were 2.30- and 7.71-times that of the CTX solution. In vivo transdermal experiments in mice showed that the amount of CTX deposited in the skin after 8 h of CTX saline administration was significantly lower than that of CTX deposited in the skin after administration of CTX-NPs. In vitro fluorescence labeling transdermal studies through Franz diffusion cells mounted with mouse abdominal skin indicated that CTX-NPs aggregated at hair follicles. Skin irritation tests in mice indicated that the irritation due to CTX-NPs was negligible. The cytotoxicity experiment showed that the viability of Balb/c 3T3 cells with CTX-NPs containing 230 µg/mL (0.08 µM) CTX was greater than 75%. CTX-NPs increase intradermal deposition of CTX by accumulating in hair follicles, which has positive implications for transdermal penetration of CTX.

Single-cell transcriptomic analysis reveals differential cell subpopulations and distinct phenotype transition in normal and dissected ascending aorta.

BACKGROUND: Acute thoracic aortic dissection (ATAD) is a fatal condition characterized by tear of intima, formation of false lumen and rupture of aorta. However, the subpopulations of normal and dissected aorta remain less studied. METHODS: Single-cell RNA sequencing was performed including 5 patients with ATAD and 4 healthy controls. Immunohistochemistry and immunofluorescence were used to verify the findings. RESULTS: We got 8 cell types from human ascending aorta and identified 50 subpopulations including vascular smooth muscle cells (VSMCs), endothelial cells, fibroblasts, neutrophils, monocytes and macrophages. Six transmembrane epithelial antigen of prostate 4 metalloreductase (STEAP4) was identified as a new marker of synthetic VSMCs. CytoTRACE identified subpopulations with higher differentiation potential in specified cell types including synthetic VSMCs, enolase 1+ fibroblasts and myeloid-derived neutrophils. Synthetic VSMCs-derived C-X-C motif chemokine ligand 12 (CXCL12) might interact with neutrophils and fibroblasts via C-X-C motif chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), respectively, which might recruit neutrophils and induce transdifferentitation of fibroblasts into synthetic VSMCs. CONCLUSION: We characterized signatures of different cell types in normal and dissected human ascending aorta and identified a new marker for isolation of synthetic VSMCs. Moreover, we proposed a potential mechanism that synthetic VSMCs might interact with neutrophils and fibroblasts via CXCL12-CXCR4/ACKR3 axis whereby deteriorating the progression of ATAD, which might provide new insights to better understand the development and progression of ATAD.

Frailty in individuals with depression, bipolar disorder and anxiety disorders: longitudinal analyses of all-cause mortality.

BACKGROUND: Frailty is a medical syndrome that is strongly associated with mortality risk and an emerging global health burden. Mental disorders are associated with reduced life expectancy and elevated levels of frailty. In this study, we examined the mortality risk associated with frailty in individuals with a lifetime history of mental disorders compared to individuals without a history of mental disorders. METHODS: The UK Biobank study recruited > 500,000 adults, aged 37-73, between 2006 and 2010. We derived the two most common albeit distinctive measures of frailty, the frailty phenotype and the frailty index. Individuals with lifetime depression, bipolar disorder or anxiety disorders were identified from multiple data sources. The primary outcome was all-cause mortality. We have also examined differences in frailty, separately by sex and age. RESULTS: Analyses included up to 297,380 middle-aged and older adults with a median follow-up of 12.19 (interquartile range = 1.31) years, yielding 3,516,706 person-years of follow-up. We observed higher levels of frailty in individuals with mental disorders for both frailty measures. Standardised mean differences in the frailty index ranged from 0.66 (95% confidence interval [CI] 0.65-0.67) in individuals with anxiety disorders to 0.94 (95% CI 0.90-0.97) in individuals with bipolar disorder, compared to people without mental disorders. For key comparisons, individuals with a mental disorder had greater all-cause mortality hazards than the comparison group without mental disorders. The highest hazard ratio (3.65, 95% CI 2.40-5.54) was observed among individuals with bipolar disorder and frailty, relative to non-frail individuals without mental disorders. CONCLUSIONS: Our findings highlight elevated levels of frailty across three common mental disorders. Frailty and mental disorders represent potentially modifiable targets for prevention and treatment to improve population health and life expectancy, especially where both conditions coexist.

The mouse resource at National Resource Center for Mutant Mice.

Mouse models are essential for dissecting disease mechanisms and defining potential drug targets. There are more than 18,500 mouse strains available for research communities in National Resource Center for Mutant Mice (NRCMM) of China, affiliated with Model Animal Research Center of Nanjing University and Gempharmatech Company. In 2019, Gempharmatech launched the Knockout All Project (KOAP) aiming to generate null mutants and gene floxed strains for all protein-coding genes in mouse genome within 5 years. So far, KOAP has generated 8,004 floxed strains and 9,769 KO (knockout) strains (updated to Oct, 2021). NRCMM also created hundreds of Cre transgenic lines, mutant knock-in models, immuno-deficient models, and humanized mouse models. As a member of the international mouse phenotyping consortium (IMPC), NRCMM provides comprehensive phenotyping services for mouse models. In summary, NRCMM will continue to support biomedical community with new mouse models as well as related services.

Development of a sandwich enzyme-linked immunosorbent kit for reliable detection of milk allergens in processed food.

The inclusion of undeclared cow's milk proteins may cause health complications to milk-allergic consumers and is one of the leading cause of food recall in many countries all over the world. Therefore, to keep control on such incidences in processed products, we established a milk sandwich ELISA test kit by incorporating two polyclonal antibodies against milk proteins obtained from different species. Its analytical effectiveness in terms of sensitivity, specificity, accuracy, trueness, and precision were all analyzed. The limit of detection (LOD) of the test kit was 0.011 ppm, with high specificity for milk protein residues. The test kit was highly specific, apart from considerable cross-reactivity with goat milk and minor cross-reactivity with donkey and horse milk. The coefficient of variation of the test kit for intra-assay ranged from 4.02% to 14.62% and inter-assay ranged from 6.05% to 15.08% respectively. The sandwich ELISA was highly specific in detecting commercial food products. In a limited retail survey, 5/6 of the milk proteins declared on the ingredient labels tested positive for milk proteins. The study offers effective technical support for the sensitive detection of milk products both for food manufacturers and regulatory authorities.

Crustacean shellfish allergens: influence of food processing and their detection strategies.

Despite the increasing popularity of crustacean shellfish among consumers due to their rich nutrients, they can induce a serious allergic response, sometimes even life-threatening. In the past decades, a variety of crustacean allergens have been identified to facilitate the diagnosis and management of crustacean allergies. Although food processing techniques can ease the risk of crustacean shellfish allergy, no available processing methods to tackle crustacean allergies thoroughly. Strict dietary avoidance of crustacean shellfish and its component is the best option for the protection of sensitized individuals, which should rely on the compliance of food labeling and, as such, on their verification by sensitive, reliable, and accurate detection techniques. In this present review, the physiochemical properties, structure aspects, and immunological characteristics of the major crustacean allergens have been described and discussed. Subsequently, the current research progresses on how various processing techniques cause the alterations and modifications in crustacean allergens to produce hypoallergenic crustacean food products were summarized and discussed. Particularly, various analytical methodologies employed in crustacean shellfish allergen detection, and the effect of food processing and matrix on these techniques, are also herein emphasized for the appropriate selection of analytical detection tools to safeguard consumers safety.

What Factors Are Associated with Symptomatic Rotator Cuff Tears: A Meta-analysis.

BACKGROUND: Rotator cuff tears are common. A previous systematic review reported on factors associated with rotator cuff tears; however, it included relatively few studies and few variables, and in addition, it had considerable heterogeneity. To identify the factors associated with symptomatic rotator cuff tears and to help guide clinicians to potentially modifiable factors, we felt a broader and more inclusive meta-analysis would be useful. QUESTIONS/PURPOSES: In this systematic review and meta-analysis, we asked what (1) demographic, (2) disease, and (3) imaging factors are associated with symptomatic rotator cuff tears? METHODS: PubMed, Embase, and Web of Science were searched, and the search period were from the inception of each database through February 2021. The keywords included "risk factor," "rotator cuff injury," "rotator cuff tears," and "rotator cuff tendinitis." All comparative studies on symptomatic rotator cuff tears were included. We considered that the diagnosis of rotator cuff tear could be made by any imaging tool (MRI or ultrasound). We considered either partial- or full-thickness tears to be a rotator cuff tear. No language restrictions were applied. Twenty-six articles from 14 countries involving 9809 individuals, consisting of 3164 patients and 6645 controls, were included. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the risk of bias of the included studies, and the highest scores were 9 and 11, respectively. The Newcastle-Ottawa Scale was used for retrospective comparative studies, and the AHRQ was used to evaluate prospective comparative studies. The eight retrospective comparative studies we included were scored from 4 to 9. The quality score of the 18 prospective comparative studies ranged from 6 to 9. Publication bias was explored using the Egger test. Heterogeneity was estimated using the I2 value. If there was no heterogeneity (I2 ≤ 50%), a fixed-effects model was used to determine the overall effect size; if there was heterogeneity (I2 > 50%), a random-effects model was used to merge the effect values. A meta-analysis was performed with RevMan 5.3, and the risk ratio (RR) and weighted mean difference of related factors were calculated. RESULTS: Our meta-analysis identified the following demographic factors associated with an increased risk of rotator cuff tears: older age (mean difference 3.1 [95% CI 1.4 to 4.8]; p < 0.001), greater BMI (mean difference 0.77 [95% CI 0.37 to 1.17]; p < 0.001), smoking (RR 1.32 [95% CI 1.17 to 1.49]; p < 0.001), dominant arm (RR 1.15 [95% CI 1.06 to 1.24]; p < 0.001), greater height (mean difference 0.9 [95% CI 0.4 to 1.4]; p < 0.001), and heavier weight (mean difference 2.24 [95% CI 0.82 to 3.66]; p = 0.002). Regarding disease factors, we found that traumatic events (RR 1.91 [95% CI 1.40 to 2.54]; p < 0.001) and hypertension (RR 1.50 [95% CI 1.32 to 1.70]; p < 0.001) were associated with symptomatic rotator cuff tears. Regarding imaging factors, we found that the following three factors were associated with symptomatic rotator cuff tears: greater acromion index (mean difference 0.11 [95% CI 0.06 to 0.16]; p < 0.001), greater critical shoulder angle (mean difference 1.9 [95% CI 1.5 to 2.3]; p < 0.001), and smaller glenoid version angle (mean difference -1.3 [95% CI -1.9 to -0.8]; p < 0.001). We found no association between the patient's sex or the presence or absence of thyroid disease and the likelihood of a rotator cuff tear being present. CONCLUSION: This study identified several factors associated with symptomatic rotator cuff tears, including blood glucose, blood pressure, weight, and smoking. Clinicians may seek to modify these factors, possibly in patients with symptomatic rotator cuff tears, but also in symptomatic patients who have not yet been diagnosed with rotator cuff tears because there would be no harm or risk associated with modifying any of the factors we identified. Future research should further study whether addressing these factors can delay the progression and size of rotator cuff tears.Level of Evidence Level III, prognostic study.

Development of a sensitive sandwich-ELISA assay for reliable detection of fish residues in foods.

A new sandwich-type Enzyme-Linked Immunosorbent Assay (ELISA) method was developed based on goat IgG as capturing antibody and rabbit IgG as detecting antibody targeting soluble antigenic fish proteins in foods as detection targets. The assay has provided a relatively lower limit of quantitation (LoQ) for fish proteins with LoQ 0.5 ng/ml and appears highly sensitive. The analysis of 24 different substances, both raw and boiled, revealed no cross-reactivity above the cut-off point of the limit of quantitation. Recoveries of the SB spiked food matrixes were in the range of 83-131%. Assay precision testing proved that repeatability (<5%) and reproducibility (<11%) had an acceptable level of variation. The sandwich ELISA was capable of detecting all tested commercially important fish. As a potential analytical tool, the newly developed immunoenzymatic method is suitable for detecting undeclared fish residues in real food samples available in the market, thereby will help to reduce the incidents of fish allergies.

Meta-analysis Comparing Celecoxib with Diclofenac Sodium in Patients with Knee Osteoarthritis.

OBJECTIVE: To compare the efficacy and safety of celecoxib and diclofenac sodium in patients with knee osteoarthritis (KOA). METHODS: Clinical controlled trials (CCTs) and randomized controlled trials (RCTs) from online databases comparing the efficacy of celecoxib and diclofenac sodium in the treatment of KOA were retrieved. The main outcomes included the treatment effect, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), visual analog scale (VAS) score, and complication rate. The Cochrane risk of bias (ROB) tool in Review Manager 5.3.5 was used to assess methodological quality. RESULTS: Twelve studies (N = 2,350) were included in this meta-analysis. The meta-analysis indicated that celecoxib reduced pain more effectively than diclofenac sodium in patients with KOA, as evaluated by the VAS score. In addition, celecoxib has certain advantages in terms of better treatment effects and greater reductions in the ESR, CRP level, and complication rate. CONCLUSIONS: Celecoxib is superior to diclofenac sodium in the treatment of KOA. However, well-designed and high-quality RCTs are still needed.

Risk factors affecting rotator cuff retear after arthroscopic repair: a meta-analysis and systematic review.

BACKGROUND: Retear after arthroscopic rotator cuff repair (ARCR) consistently challenges medical staff and patients, and the incidence of retear after surgery is 10%-94%. The purpose of this study was to identify the risk factors that cause retear after ARCR and provide theoretical guidance for clinical intervention to reduce the occurrence of postoperative rotator cuff retear. METHODS: The protocol for this meta-analysis was registered with PROSPERO (CRD42021225088). PubMed, Web of Science, and Embase were searched for observational studies on risk factors for rotator cuff retear after arthroscopic repair. Meta-analytical methods were used to determine the odds ratio or weighted mean difference of potential risk factors related to postoperative rotator cuff retear. Stata 15.1 was used to quantitatively evaluate the publication bias of the statistical results. RESULTS: Fourteen studies from 6 countries with a total of 5693 patients were included. The meta-analysis revealed that the risk factors for retear after rotator cuff repair were age, body mass index, diabetes, subscapularis and infraspinatus fatty infiltration, symptom duration, bone mineral density, tear length, tear width, tear size area, amount of retraction, critical shoulder angle, acromiohumeral interval, distance from the musculotendinous junction to the glenoid, operative duration, biceps procedure, and postoperative University of California Los Angeles shoulder score. CONCLUSION: These findings can help clinical medical staff identify patients who are prone to retear early after arthroscopic repair and develop targeted prevention and treatment strategies for modifiable risk factors, which are of great significance for reducing the occurrence of rotator cuff retear after ARCR.