Diffusion-based deep learning method for augmenting ultrastructural imaging and volume electron microscopy.

Electron microscopy (EM) revolutionized the way to visualize cellular ultrastructure. Volume EM (vEM) has further broadened its three-dimensional nanoscale imaging capacity. However, intrinsic trade-offs between imaging speed and quality of EM restrict the attainable imaging area and volume. Isotropic imaging with vEM for large biological volumes remains unachievable. Here, we developed EMDiffuse, a suite of algorithms designed to enhance EM and vEM capabilities, leveraging the cutting-edge image generation diffusion model. EMDiffuse generates realistic predictions with high resolution ultrastructural details and exhibits robust transferability by taking only one pair of images of 3 megapixels to fine-tune in denoising and super-resolution tasks. EMDiffuse also demonstrated proficiency in the isotropic vEM reconstruction task, generating isotropic volume even in the absence of isotropic training data. We demonstrated the robustness of EMDiffuse by generating isotropic volumes from seven public datasets obtained from different vEM techniques and instruments. The generated isotropic volume enables accurate three-dimensional nanoscale ultrastructure analysis. EMDiffuse also features self-assessment functionalities on predictions' reliability. We envision EMDiffuse to pave the way for investigations of the intricate subcellular nanoscale ultrastructure within large volumes of biological systems.

A systematic review and meta-analysis of acupuncture for De Quervain's tenosynovitis treatment.

BACKGROUND: De Quervain's tenosynovitis (DQt) is a prevalent chronic inflammatory musculoskeletal disorder predominantly affecting the radial aspect of the wrist. This study conducted a comprehensive review of the efficacy of acupuncture in treating De Quervain's tenosynovitis (DQt). Although there is evidence suggesting that acupuncture can alleviate symptoms of DQt-characterized by pain, swelling, and functional impairment-higher-level evidence is still required to further substantiate its efficacy and safety. This study conducted a comprehensive review of the efficacy of acupuncture in treating De Quervain's tenosynovitis (DQt). METHODS: By systematically searching databases such as PubMed, Science Direct, Web of Science, Google Scholar, EMbase, PEDro, China National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Chongqing VIP China Science, Technology Journal Database (VIP), we retrieved randomized controlled trial (RCT) literature on acupuncture for DQt, with the search period extending to November 1, 2023. After extracting and assessing data from the included literature, we performed Meta-analysis using RevMan 5.4.1 software. RESULTS: The results encompassed 14 RCT papers, involving 851 patients. The Meta-analysis findings indicated that, when compared to topical analgesics, acupuncture demonstrated a significant increase in treatment effectiveness (RR = 1.24; 95% CI = 1.11, 1.39, P = 0.0002) and a notable reduction in VAS pain scores (MD = -1.06; 95% CI = -1.51, -0.61, P < 0.00001). However, no statistically significant difference was observed in conney wrist joint scores. Furthermore, acupuncture was found to reduce VAS pain scores compared to the waiting list group. In comparison to corticosteroid injections (CSI), acupuncture did not show statistical significance in VAS, effectiveness rate, and conney wrist scores. CONCLUSION: Acupuncture exhibited a promising trend in alleviating pain associated with DQt and enhancing treatment effectiveness. Nonetheless, due to limitations in the quantity and quality of the included studies, these findings warrant further validation through additional research.

Modic Changes Increase the Cage Subsidence Rate in Spinal Interbody Fusion Surgery: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To compare the effect of different Modic changes (MC) grades on the cage subsidence rate after spinal interbody fusion surgery. METHODS: We comprehensively searched the PubMed, Embase, and Web of Science databases from inception to August 13, 2023, for relevant randomized controlled trials and prospective and retrospective cohort studies. Review Manager 5.3 and STATA13.0 were used to conduct this meta-analysis. The subsidence rate was assessed using relative risk and 95% confidence intervals. RESULTS: Six studies with a total of 716 segments were allocated to four groups according to the type of MC. The subsidence rate in the non-Modic changes (NMC) was significantly lower than that in the MC. The subsidence rate in the NMC was significantly lower than that in the MC in the subgroup of cages with extra instrumentation. No significant difference was identified between the 2 groups in the oblique lumbar interbody fusion subgroup. The subsidence rate in the NMC was significantly lower than that in the MC in the transforaminal lumbar interbody fusion subgroup. The subsidence rate in the NMC was significantly lower than that in the MC1 and MC2. We found no significant difference between NMC and MC3, MC1 and MC2, MC1 and MC3, or MC2 and MC3. CONCLUSIONS: MC may be associated with a higher cage subsidence rate. With the increase in MC grades, the incidence of subsidence decreased gradually, but it was always higher than that in the NMC. Oblique lumbar interbody fusion may be a better choice for the treatment of lumbar degenerative disease with MC.

Synthesis of Tröger's base-based [3]arenes for efficient iodine adsorption.

Enantiomers of Tröger's base-based [3]arenes R6N-E[3] and S6N-E[3] were synthesized successfully as two optically pure Tröger's base-based macrocycles in which three Tröger's base subunits were incorporated. Among these Tröger's base-based[3]arenes, M[3] showed high absorption of iodine up to 4.02 g g-1 in vapor.

ADR3, a next generation i-body to human RANKL, inhibits osteoclast formation and bone resorption.

Osteoporosis is a chronic skeletal condition characterized by low bone mass and deteriorated microarchitecture of bone tissue and puts tens of millions of people at high risk of fractures. New therapeutic agents like i-bodies, a class of next-generation single-domain antibodies, are needed to overcome some limitations of conventional treatments. An i-body is a human immunoglobulin scaffold with two long binding loops that mimic the shape and position of those found in shark antibodies, the variable new antigen receptors of sharks. Its small size (∼12 kDa) and long binding loops provide access to drug targets, which are considered undruggable by traditional monoclonal antibodies. Here, we have successfully identified a human receptor activator of nuclear factor-κB ligand (RANKL) i-body, ADR3, which demonstrates a high binding affinity to human RANKL (hRANKL) with no adverse effect on the survival or proliferation of bone marrow-derived macrophages. Differential scanning fluorimetry suggested that ADR3 is stable and able to tolerate a wide range of physical environments (including both temperature and pH). In addition, in vitro studies showed a dose-dependent inhibitory effect of ADR3 on osteoclast differentiation, podosome belt formation, and bone resorption activity. Further investigation on the mechanism of action of ADR3 revealed that it can inhibit hRANKL-mediated signaling pathways, supporting the in vitro functional observations. These clues collectively indicate that hRANKL antagonist ADR3 attenuates osteoclast differentiation and bone resorption, with the potential to serve as a novel therapeutic to protect against bone loss.

Transcriptome analysis reveals potential key immune genes of Hong Kong oyster (Crassostrea hongkongensis) against Vibrio parahaemolyticus infection.

Hong Kong oyster (Crassostrea hongkongensis) is one of the main species of economic shellfish cultivated in the coastal areas of southern China. The cultivation of this shellfish may be adversely impacted by Vibrio parahaemolyticus, a harmful pathogenic bacterium for many mariculture species, as it usually exists on the surface of Hong Kong oysters. Although previous studies have discovered that oysters rely on non-specific immune system to fight pathogen invasion, the genes corresponding to the complex immune system against Vibrio is still not fully elucidated. Therefore, we conducted a transcriptome analysis on the gill from Hong Kong oysters at two time points (i.e., 12 h and 24 h after V. parahaemolyticus or PBS challenge) to identify potential immune genes against V. parahaemolyticus infection. A total of 61779 unigenes with the average length of 1221 bp were obtained, and the annotation information of 39917 unigenes were obtained from Nr, SwissProt, KEGG and COG/KOG. After a pairwise comparison between V. parahaemolyticus or PBS challenge at the two time points, three groups of differentially expressed genes induced by V. parahaemolyticus were captured and analyzed. GO and KEGG analyses showed that multiple immune-related genes played an important role in pathogen infection, including HSP70, PCDP3 and TLR4. Furthermore, genes annotation indicated that LITAF, TNFSF10, Duox2 and big defensin family are also involved in immune regulation. Our study provides a reference for further exploration the molecular mechanism that defenses the pathogen infection regarding the identified immune-related genes in Hong Kong oysters.

Expressions of melanopsins in telencephalon imply their function in synchronizing semilunar spawning rhythm in the mudskipper Boleophthalmus pectinirostris.

The mudskipper Boleophthalmus pectinirostris inhabits intertidal mudflats, exhibiting semilunar reproductive rhythms. To investigate whether melanopsin is possibly involved in the synchronization of the semilunar spawning rhythm in the female mudskipper, we first cloned all four melanopsin subtypes (opn4m1, opn4m3, opn4x1, opn4x2) in B. pectinirostris. Results from RTq-PCR showed that significantly higher transcription levels of all four melanopsin subtypes were observed in the eyes rather than other tissues. In brain, all four melanopsin subtypes were also detectable in different regions, including the telencephalon, in which the expression of melanopsin has not been reported in other teleosts. The transcription levels of opn4m3 and opn4x1 in the telencephalon exhibited a daily fluctuation pattern. When females entered the spawning season, opn4m1 and opn4x1 transcript levels increased significantly in the telencephalon. During the spawning season, the transcript levels of opn4m3 and opn4x1 in the telencephalon appeared to have a cyclic pattern associated with semilunar periodicity, exhibiting two cycles with a peak around the first or the last lunar quarters. Results from ISH showed that, opn4x1 mRNA was localized in the medial of dorsal telencephalic area, dorsal nucleus of ventral telencephalic area (Vd), ventral nucleus of ventral telencephalic area (Vv), anterior part of parvocellular preoptic nucleus, magnocellular part of the magnocellular preoptic nucleus (PMmc), habenular and ventral zone of hypothalamus. Intriguingly, gnrh3 mRNA was also located in Vd, Vv and PMmc. Taken together, our results suggested that melanopsins, e.g. opn4x1, expressed in the telencephalon might mediate semilunar spawning activity in the female mudskipper.

Reliability and validity of the Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) in Chinese people.

OBJECTIVE: To investigate the reliability and validity of Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) for different population cohorts in the city of Guangzhou, Guangdong, China and to provide evidence and tools for further evaluation of healthy fitness of Chinese population and related factors. DESIGN: Cross-sectional study. SETTING: Urban neighbourhood and Medical University. PARTICIPANTS: Elderly people (n=393; mean age 68.27±6.38 years; 53.18% male), university students (n=390; mean age 19.29±1.29 years; 38.21% male) and urban residents (n=393; mean age 32.23±9.41 years; 44.78% male). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were evaluated the reliability and validity of HFMS V1.0 by internal consistency evaluation, split-half reliability, test-retest reliability, convergent and discriminant construct validity, and factor analysis. RESULTS: The Cronbach's α coefficients for HFMS V1.0 were all greater than 0.85 for overall scale of total samples and three individual groups, and the split-half reliability and intragroup correlation coefficients were both greater than 0.70 (p<0.01). The correlation of each item, dimension and subscales ranged from 0.52 to 0.91 (p < 0.01). A total of 10 factors were screened by exploratory factor analysis with the cumulative contribution rate of 61.40%, basically consistent with the theoretical structure of scale. The confirmatory factor analysis indicated good fit: CMIN/DF=3.45, root mean square error of approximation=0.05, GFI=0.91, AGFI=0.90, IFI=0.90, comparative fit index=0.90. CONCLUSION: HFMS V1.0 showed acceptable reliability and validity in the test of healthy fitness of general population in Guangzhou. This scale could be a reliable measurement tool for evaluation of healthy fitness and potential risk factors.

Reliability and validity of Healthy Fitness Measurement Scale Version1.0 (HFMS V1.0) in Chinese elderly people.

PURPOSE: We examined the reliability and validity of the Healthy Fitness Measurement Scale Version 1.0 (HFMS V1.0) specifically on elderly people in China. METHODS: We carried out a cross-sectional study in December 2020 and enrolled 800 elderly people through stratified sampling technique, including 777 valid samples (with a mean age of 71.81 ± 8.36 years), of which 382 cases (49.2%) were women. The level of healthy fitness was measured using the HFMS V1.0. The Cronbach's alpha coefficient, split-half reliability, test-retest reliability, convergent and discriminant validity, exploratory factor and confirmatory factor were calculated for assessing the reliability and validity of HFMS V1.0. RESULTS: HFMS V1.0 consists of 8 dimensions and 38 items. The scale had acceptable reliability (Cronbach's alpha = 0.920, split-half = 0.946, test-retest = 0.878). Exploratory factor analysis showed KMO value =0.927, and uncovered 10 factors with the cumulative contribution rate of 65.71% and all factor loads over 0.40. The item distribution was consistent with the initial expectation of the scale. The confirmatory factor analysis indicated good fit: CMIN/DF = 2.796, RMSEA = 0.048, IFI =0.914, TLI = 0.902, CFI = 0.913. CONCLUSION: HFMS V1.0 was shown to have acceptable reliability and validity indices for this sample. Collectively, HFMS V1.0 is reliable and efficient to measure the healthy fitness of elderly people. It is recommended to use it among the elderly in other Chinese cities in the future to ensure uniformity and objectivity. This scale can be carried out to evaluate of the effectiveness of public health measures in improving the healthy fitness level of the elderly and optimizing public health policies.

The effect of Chinese herbal medicine on digestive system and liver functions should not be neglected in COVID-19: An updated systematic review and meta-analysis.

Gastrointestinal symptoms and liver injury are common in patients with coronavirus disease 2019 (COVID-19). However, profiles of different pharmaceutical interventions used are relatively underexplored. Chinese herbal medicine (CHM) has been increasingly used for patients with COVID-19, but the efficacy of CHM used in COVID-19 on gastrointestinal symptoms and liver functions has not been well studied with definitive results based on the updated studies. The present study aimed at testing the efficacy of CHM on digestive symptoms and liver function (primary outcomes), the aggravation of COVID-19, and the time to viral assay conversion (secondary outcomes), among patients with COVID-19, compared with standard pharmacotherapy. The literature search was undertaken in 11 electronic databases from December 1, 2019 up to November 8, 2020. Appraisal of the evidence was conducted with Cochrane risk of bias tool or Newcastle Ottawa Scale. A random-effects model or subgroup analysis was conducted when significant heterogeneity was identified in the meta-analysis. The certainty of the evidence was assessed with the grading of recommendations assessment, development, and evaluation approach. Forty-eight included trials involving 4,704 participants were included. Meta-analyses favored CHM plus standard pharmacotherapy for COVID-19 on reducing the aggravation of COVID-19 and the time to viral assay conversion compared with standard pharmacotherapy. However, the present CHM as a complementary therapy for treating COVID-19 may not be beneficial for improving most gastrointestinal symptoms and liver function based on the current evidence. More well-conducted trials are warranted to confirm the potential efficacy of CHM furtherly.

[Reliability and validity of Healthy Fitness Measurement Scale (V1.0) for evaluating healthy fitness of college students in Guangzhou].

OBJECTIVE: To evaluate the reliability and validity of Healthy Fitness Measurement Scale V1.0 (HFMS V1.0) for assessing healthy fitness status of college students in Guangzhou. METHODS: A total of 584 college students were evaluated with HFMS V1.0. The reliability and validity of HFMS V1.0 scale were assessed for its discrimination degree, Cronbach α coefficient, split-half reliability, test-retest reliability, content validity, structural validity, calibration validity and responsiveness. RESULTS: The Cronbach α of HFMS V1.0 scale was 0.893, the split-half coefficient was 0.909, and the test-retest coefficient was 0.923. The correlation coefficients of each dimension with its subscales ranged from 0.687 to 0.931. The correlation coefficient between each item and its dimension ranged from 0.558 to 0.863(P < 0.05). Exploratory factor analysis showed that the variance interpretation of 8 factors was 55.105%, and the factor structure was basically identical with the theoretical concept of the scale. Confirmatory factor analysis showed excellent goodness-of-fit indices of the model (χ2/DF= 1.952; RMSEA=0.400; GFI=0.906; TLI=0.905; IFI=0.914; and CFI=0.913; P < 0.05). The correlation coefficients between the 4 general items and their corresponding scales ranged from 0.585 to 0.670. The proportions of the highest and lowest scores of the scale were very low, suggesting a high responsiveness of the scale. CONCLUSIONS: HFMS V1.0 has high reliability and validity for evaluating healthy fitness status of college students.

A missense mutation sheds light on a novel structure-function relationship of RANKL.

The tumor necrosis factor (TNF)-like core domain of receptor activator of nuclear factor-κB ligand (RANKL) is a functional domain critical for osteoclast differentiation. One of the missense mutations identified in patients with osteoclast-poor autosomal recessive osteopetrosis (ARO) is located in residue methionine 199 that is replaced with lysine (M199K) amid the TNF-like core domain. However, the structure-function relationship of this mutation is not clear. Sequence-based alignment revealed that the fragment containing human M199 is highly conserved and equivalent to M200 in rat. Using site-directed mutagenesis, we generated three recombinant RANKL mutants M200K/A/E (M200s) by replacing the methionine 200 with lysine (M200K), alanine (M200A), and glutamic acid (M200E), representative of distinct physical properties. TRAcP staining and bone pit assay showed that M200s failed to support osteoclast formation and bone resorption, accompanied by impaired osteoclast-related signal transduction. However, no antagonistic effect was found in M200s against wild-type rat RANKL. Analysis of the crystal structure of RANKL predicted that this methionine residue is located within the hydrophobic core of the protein, thus, likely to be crucial for protein folding and stability. Consistently, differential scanning fluorimetry analysis suggested that M200s were less stable. Western blot analysis analyses further revealed impaired RANKL trimerization by M200s. Furthermore, receptor-ligand binding assay displayed interrupted interaction of M200s to its intrinsic receptors. Collectively, our studies revealed the molecular basis of human M199-induced ARO and elucidated the indispensable role of rodent residue M200 (equivalent to human M199) for the RANKL function.

Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis.

Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has anti-inflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-κB and Ca2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.

Cycloastragenol Attenuates Osteoclastogenesis and Bone Loss by Targeting RANKL-Induced Nrf2/Keap1/ARE, NF-κB, Calcium, and NFATc1 Pathways.

Osteoporosis, which typically affects postmenopausal women, is an osteolytic disease due to over-activation of osteoclasts. However, current drugs targeting osteoclast inhibition face various side effects, making natural compounds with great interest as alternative treatment options. Cycloastragenol (CAG) is a triterpenoid with multiple biological activities. Previously, CAG's activity against aging-related osteoporosis was reported, but the mechanisms of actions for the activities were not understood. This study demonstrated that CAG dose-dependently inhibited osteoclast formation in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated bone marrow macrophage (BMMs). Mechanism studies showed that CAG inhibited NF-κB, calcium, and nuclear factor of activated T cells 1 (NFATc1) pathways. Additionally, CAG also promoted the nuclear factor-erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/anti-oxidative response element (ARE) pathway that scavenges reactive oxygen species (ROS). Furthermore, CAG was also found to prevent bone loss of postmenopausal osteoporosis (PMO) in a preclinical model of ovariectomized (OVX) mice. Collectively, our research confirms that CAG inhibits the formation and function of osteoclasts by regulating RANKL-induced intracellular signaling pathways, which may represent a promising alternative for the therapy of osteoclast-related disease.

The molecular structure and function of sorting nexin 10 in skeletal disorders, cancers, and other pathological conditions.

SNX10 is a member of the phox homology domain-containing family of phosphoinositide-binding proteins. Intracellularly, SNX10 localizes to endosomes where it mediates intracellular trafficking, endosome organization, and protein localization to the centrosome and cilium. It is highly expressed in bone and the gut where it participates in bone mineral and calcium homeostasis through the regulation of osteoclastic bone resorption and gastric acid secretion, respectively. Not surprisingly, patients harboring mutations in SNX10 mutation manifest a phenotype of autosomal recessive osteopetrosis or malignant infantile osteopetrosis, which is clinically characterized by dense bones with increased cortical bone into the medullary space with bone marrow occlusion or depletion, bone marrow failure, and anemia. Accordingly, SNX10 mutant osteoclasts exhibit impaired bone resorptive capacity. Beyond the skeleton, there is emerging evidence implicating SNX10 in cancer development, metabolic disorders, inflammation, and chaperone-mediated autophagy. Understanding the structural basis through which SNX10 exerts its diverse biological functions in both cell and tissue-specific manners may therefore inform new therapeutic opportunities toward the treatment and management of SNX10-related diseases.

PKC-δ deficiency in B cells displays osteopenia accompanied with upregulation of RANKL expression and osteoclast-osteoblast uncoupling.

PKC-δ is an important molecule for B-cell proliferation and tolerance. B cells have long been recognized to play a part in osteoimmunology and pathological bone loss. However, the role of B cells with PKC-δ deficiency in bone homeostasis and the underlying mechanisms are unknown. We generated mice with PKC-δ deletion selectively in B cells by crossing PKC-δ-loxP mice with CD19-Cre mice. We studied their bone phenotype using micro-CT and histology. Next, immune organs were obtained and analyzed. Western blotting was used to determine the RANKL/OPG ratio in vitro in B-cell cultures, ELISA assay and immunohistochemistry were used to analyze in vivo RANKL/OPG balance in serum and bone sections respectively. Finally, we utilized osteoclastogenesis to study osteoclast function via hydroxyapatite resorption assay, and isolated primary calvaria osteoblasts to investigate osteoblast proliferation and differentiation. We also investigated osteoclast and osteoblast biology in co-culture with B-cell supernatants. We found that mice with PKC-δ deficiency in B cells displayed an osteopenia phenotype in the trabecular and cortical compartment of long bones. In addition, PKC-δ deletion resulted in changes of trabecular bone structure in association with activation of osteoclast bone resorption and decrease in osteoblast parameters. As expected, inactivation of PKC-δ in B cells resulted in changes in spleen B-cell number, function, and distribution. Consistently, the RANKL/OPG ratio was elevated remarkably in B-cell culture, in the serum and in bone specimens after loss of PKC-δ in B cells. Finally, in vitro analysis revealed that PKC-δ ablation suppressed osteoclast differentiation and function but co-culture with B-cell supernatant reversed the suppression effect, as well as impaired osteoblast proliferation and function, indicative of osteoclast-osteoblast uncoupling. In conclusion, PKC-δ plays an important role in the interplay between B cells in the immune system and bone cells in the pathogenesis of bone lytic diseases.

Comparison of arthroscopic single-row and double-row repair in the treatment of rotator cuff tears: A protocol of cohort analysis.

BACKGROUND: Single-row (SR) and double-row (DR) techniques are 2 kinds of widely used approaches for the arthroscopic repair of rotator cuff. This retrospective clinical trial was performed to address the question of whether a DR rotator cuff anchor repair gives results superior to a SR anchor repair in clinical outcome scores and complication rates. METHODS: This study was performed and reported in accordance with the Strengthening the Reporting of Observational studies in Epidemiology checklist. We retrospectively reviewed our database, which was collected prospectively. From 2014 to 2017, 264 patients underwent arthroscopic rotator cuff repair by an experienced single shoulder surgeon with the SR and DR techniques. This study was approved by the institutional review board in our hospital and was registered in the Research Registry. Outcome measures included Constant-Murley score, muscle strength, patient satisfaction, passive range of motion, and retear rates. RESULTS: The hypothesis was that the DR technique would achieve better functional scores and fewer complications as compared to the SR technique in treatment of rotator cuff tears.

All-inside versus inside-out suture techniques in arthroscopic meniscus repair: A prospective randomized study protocol.

BACKGROUND: With advancements in our understanding of meniscal function, treatment options for meniscal injuries have evolved considerably over the past few decades. The aim of the current study was to compare the all-inside and inside-out techniques with regard to retear rate, functional outcomes, and perioperative complications in patients who had undergone arthroscopic meniscus repair. We hypothesized that there was no significant difference between the 2 groups in terms of postoperative outcomes after arthroscopic meniscus repair. METHODS: This study was a prospective randomized blinded study, with a parallel design and an allocation ratio of 1:1 for the treatment groups. This study was approved by the Institutional Review Board in our hospital and written informed consent was obtained from all subjects participating in the trial. It was carried out in accordance with the principles of the Helsinki Declaration. A total of 70 patients who meet inclusion criteria are randomized to either all-inside or inside-out group. The primary outcome measure was retear rate. Retear was determined by repeat arthroscopic evaluation of patients with follow-up for symptoms of persistent or new pain, catching, or locking that was possibly related to the meniscal repair. Secondary outcomes included disease-specific quality of life measurement with the Western Ontario Meniscal Evaluation Tool, range of motion, operative time, and adverse events at surgery or throughout the follow-up period. RESULTS: This study has limited inclusion and exclusion criteria and a well-controlled intervention. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5589).

Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation.

Osteoporosis, characterized by disrupted bone resorption and formation, is viewed as a global health challenge. Arctiin (ARC) is a main component of Arctium lappa L, which exerts chemopreventive effects against various tumor cells. However, the role of ARC in bone remodeling is still unclear. Here, we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-κB ligand (RANKL) in a dose- and time-dependent manner without exerting cytotoxic effects. Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways, but also enhances the expression of cytoprotective enzymes that are involved in scavenging reactive oxygen species (ROS). Further, ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclast formation. Preclinical studies showed that ARC protects bone loss in an ovariectomy (OVX) mouse model. Conclusively, our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway, thereby2 preventing OVX-induced bone loss. Thus, ARC may serve as a novel therapeutic agent for the treatment of osteoporosis.