Electroacupuncture versus exercise in patients with knee osteoarthritis: Study protocol for a randomized controlled trial.

PURPOSE: Knee osteoarthritis (KOA) is a common disorder among middle and older individuals. Electroacupuncture and exercise are present as two popular physical therapies for the management of KOA, and both were demonstrated to produce considerable results. However, the clinical decision-making process between these therapeutic interventions remains challenging due to the limited evidence of distinctions in their respective effects. This study aims to evaluate the clinical effect and cost effectiveness of electroacupuncture versus exercise in patients with KOA. STUDY DESIGN AND METHODS: This is a randomized controlled trial in which 196 symptomatic KOA patients will be randomly assigned 1:1 either to the electroacupuncture group (n = 98) and the exercise group (n = 98). Patients in the electroacupuncture group will receive acupuncture with electric stimulation 3 times a week for 8 weeks, whereas patients in the exercise group will receive neuromuscular training twice a week for 8 weeks. Education concerning KOA management will be provided in both therapies. Co-primary outcomes include changes in numerical rating scale (NRS) and Knee injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) subscale from baseline at week 8. Secondary outcomes include KOOS Pain subscale, KOOS knee-related Quality of Life (QOL) subscale, Short Form 6 Dimensions (SF-6D), five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), Credibility/ Expectancy Questionnaire, Patient's global assessment (PGA), 30-second Chair Stand Test (30s-CST), 40m (4*10m) Fast Paced Walk Test (40m FPWT), and Daily Physical Activity level (DPA). DISCUSSION: The results of this study will provide evidence regarding differences between these 2 physical therapies in multiple aspects and will provide specific guidance for the development of treatments based on the needs of individual patients. TRIAL REGISTRATION: ChiCTR2300070376.

Prevalence of T-2 Toxin in the Food and Beverages of Residents Living in a Kashin-Beck-Disease Area of Qamdo, Tibet.

It has been strongly suggested that selenium deficiency and T-2 toxin contamination have a strong relationship with the occurrence and development of Kashin-Beck disease (KBD). In order to provide information for understanding the high prevalence of KBD in Tibet, this study collected the responses to a cubital venous blood and dietary questionnaire of 125 subjects including 75 KBD patients and 50 healthy controls in a KBD-prevalent county (Luolong County) in Tibet, China. A total of 10 household local families were randomly selected in this area, and local diet samples of brick tea, Zanba powder, milk residue, and hulless Barley were collected from these residents. Selenium content in blood was detected by inductively coupled plasma mass spectrometry (ICP-MS). The T-2 toxin contamination level in food sample was assayed using an ELISA kit. The selenium levels of patients and controls were 42.0 ± 19.8 and 56.06 ± 22.4 µg/L, respectively. The serum selenium level in controls was higher than that in patients, but there was no significant difference, and the serum selenium level both in patients and controls in Tibet was lower than the normal range. The results of the dietary survey showed that the number of respondents who consumed butter tea was large; 46.67% of patients indicated that they drank buttered tea every day, which was significantly higher than in controls. The contents of T-2 toxin in Zanba powder, milk residue, hulless barley and drinking water samples were below the detection limit (0.05 µg/kg); this result was labeled Tr. Unexpectedly, the contents of T-2 toxin in brick tea were higher, with average levels of 424 ± 56 µg/kg in Detong village and 396 ± 24 µg/kg in Langcuo village. For the first time, we report the presence of an extremely high concentration of T-2 toxin in brick tea of Tibet.

Identification of a cinnamoyl-CoA reductase from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis.

MAIN CONCLUSION: The identification of a functional cinnamoyl-CoA reductase enzyme from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis offers the potential for enhancing trans-cinnamaldehyde production through genetic engineering. A significant accumulation of trans-cinnamaldehyde has been found in the bark tissues of C. cassia, used in traditional Chinese medicine. trans-Cinnamaldehyde exhibits various pharmacological properties such as anti-inflammatory, analgesic, and protection of the stomach and the digestive tract. However, further elucidation and characterization of the biosynthetic pathway for trans-cinnamaldehyde is required. In this study, we conducted an integrated analysis of trans-cinnamaldehyde accumulation profiles and transcriptomic data from five different C. cassia tissues to identify the genes involved in its biosynthesis. The transcriptome data we obtained included nearly all genes associated with the trans-cinnamaldehyde pathway, with the majority demonstrating high abundance in branch barks and trunk barks. We successfully cloned four C. cassia cinnamoyl-CoA reductases (CcCCRs), a key gene in trans-cinnamaldehyde biosynthesis. We found that the recombinant CcCCR1 protein was the only one that more efficiently converted cinnamoyl-CoA into trans-cinnamaldehyde. CcCCR1 exhibited approximately 14.7-fold higher catalytic efficiency (kcat/Km) compared to the Arabidopsis thaliana cinnamoyl-CoA reductase 1 (AtCCR1); therefore, it can be utilized for engineering higher trans-cinnamaldehyde production as previously reported. Molecular docking studies and mutagenesis experiments also validated the superior catalytic activity of CcCCR1 compared to AtCCR1. These findings provide valuable insights for the functional characterization of enzyme-coding genes and hold potential for future engineering of trans-cinnamaldehyde biosynthetic pathways.

Evaluation of genetic response of mesenchymal stem cells to nanosecond pulsed electric fields by whole transcriptome sequencing.

BACKGROUND: Mesenchymal stem cells (MSCs) modulated by various exogenous signals have been applied extensively in regenerative medicine research. Notably, nanosecond pulsed electric fields (nsPEFs), characterized by short duration and high strength, significantly influence cell phenotypes and regulate MSCs differentiation via multiple pathways. Consequently, we used transcriptomics to study changes in messenger RNA (mRNA), long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA expression during nsPEFs application. AIM: To explore gene expression profiles and potential transcriptional regulatory mechanisms in MSCs pretreated with nsPEFs. METHODS: The impact of nsPEFs on the MSCs transcriptome was investigated through whole transcriptome sequencing. MSCs were pretreated with 5-pulse nsPEFs (100 ns at 10 kV/cm, 1 Hz), followed by total RNA isolation. Each transcript was normalized by fragments per kilobase per million. Fold change and difference significance were applied to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate gene functions, complemented by quantitative polymerase chain reaction verification. RESULTS: In total, 263 DEGs were discovered, with 92 upregulated and 171 downregulated. DEGs were predominantly enriched in epithelial cell proliferation, osteoblast differentiation, mesenchymal cell differentiation, nuclear division, and wound healing. Regarding cellular components, DEGs are primarily involved in condensed chromosome, chromosomal region, actin cytoskeleton, and kinetochore. From aspect of molecular functions, DEGs are mainly involved in glycosaminoglycan binding, integrin binding, nuclear steroid receptor activity, cytoskeletal motor activity, and steroid binding. Quantitative real-time polymerase chain reaction confirmed targeted transcript regulation. CONCLUSION: Our systematic investigation of the wide-ranging transcriptional pattern modulated by nsPEFs revealed the differential expression of 263 mRNAs, 2 miRNAs, and 65 lncRNAs. Our study demonstrates that nsPEFs may affect stem cells through several signaling pathways, which are involved in vesicular transport, calcium ion transport, cytoskeleton, and cell differentiation.

Enhanced bone regeneration via endochondral ossification using Exendin-4-modified mesenchymal stem cells.

Nonunions and delayed unions pose significant challenges in orthopedic treatment, with current therapies often proving inadequate. Bone tissue engineering (BTE), particularly through endochondral ossification (ECO), emerges as a promising strategy for addressing critical bone defects. This study introduces mesenchymal stem cells overexpressing Exendin-4 (MSC-E4), designed to modulate bone remodeling via their autocrine and paracrine functions. We established a type I collagen (Col-I) sponge-based in vitro model that effectively recapitulates the ECO pathway. MSC-E4 demonstrated superior chondrogenic and hypertrophic differentiation and enhanced the ECO cell fate in single-cell sequencing analysis. Furthermore, MSC-E4 encapsulated in microscaffold, effectively facilitated bone regeneration in a rat calvarial defect model, underscoring its potential as a therapeutic agent for bone regeneration. Our findings advocate for MSC-E4 within a BTE framework as a novel and potent approach for treating significant bone defects, leveraging the intrinsic ECO process.

Multidimensional characteristics of musculoskeletal pain and risk of hip fractures among elderly adults: the first longitudinal evidence from CHARLS.

BACKGROUND: Hip fractures are a major public health concern among middle-aged and older adults. It is important to understand the associated risk factors to inform health policies and develop better prevention strategies. Musculoskeletal pain is a possible implicating factor, being associated with physical inactivity and risk of falls. However, the association between musculoskeletal pain and hip fractures has not been clearly investigated. METHODS: A nationally representative sample of the Chinese population was obtained from the China Health and Retirement Longitudinal Study (CHARLS). The study collected patient information on their demographic characteristics, socioeconomic status, other health-related behavior, and history of musculoskeletal pain and hip fractures. Univariate and multivariate analyses were conducted to investigate the factors influencing the risk of hip fracture, including factors related to the individual and to musculoskeletal pain. P for trend test was performed to assess the trend of each continuous variable. The robustness and bias were assessed using the bootstrap method. Restricted cubic spline regression was utilized to identify linear or non-linear relationships. RESULTS: Among the 18,813 respondents, a total of 215 individuals reported that they have experienced a hip fracture. An increased risk of hip fracture was associated with the presence of waist pain and leg pain (P < 0.05), as well as with an increased number of musculoskeletal pain sites (P < 0.05). For individuals aged 65 and above, a significant association was found between age and the risk of hip fracture (P < 0.05). Furthermore, respondents with lower education level had a higher risk of hip fracture compared to those with higher education levels (P < 0.05). CONCLUSION: In the Chinese population, the risk of hip fracture was found to be associated with both the location and extent of musculoskeletal pain, as well as with other factors such as age and demographic characteristics. The findings of this study may be useful for informing policy development and treatment strategies, and provide evidence for comparison with data from other demographic populations.

[Analysis of diet structure of Kashin-beck disease area in Chamdo-Lhorong of Tibet in 2021].

OBJECTIVE: To investigate and compare the dietary structure between healthy people and patients in KBD area of Chamdo-Lhorong of Tibet. METHODS: A case-control study design was used, retrospectively select patients who had completed screening and registered in the national Kashin-Beck Disease surveillance system in 2021 in Luolong County, Qamdo, Tibet as the source population of the case group, and randomly selected people who had not been screened for Kashin-Beck disease in the same county as the control group. The self-made diet questionnaire was used to record the types of food consumption, frequency of food intake, basic information of the respondents, family size and other basic information in the past year by one-on-one interview. RESULTS: The staple food with the highest response among the patients(97.33%) was rice(rice/rice noodle), and the highest response among the healthy people(90%) was non-wheat products, non-fried pasta(bread/steamed bun/noodles/dumplings), except instant noodles.78.7% of patients chose not to eat local wheat(Tibetan noodles), and the number of non-patients who chose to eat non-local wheat(Tibetan noodles) 3-4 times a week was significantly higher than that of patients. The meat and meat products with the highest response in both patients(93.33%) and healthy people(90%) was yak meat(local). The control group also chose to consume beef(non-local/lamb/mutton/other non-processed meat), poultry and livestock offal, fish(all seawater and freshwater fish), shrimp and crabs or other seafood, and their consumption rate and intake frequency were significantly higher than those of the case group. The consumption rate and frequency of tomato, onion and garlic(garlic shoots/leek/onion/onion) and fresh eggs(egg/duck egg/quail egg/goose egg) in control group were significantly higher than those in case group. There was no significant difference in consumption rate and frequency of fruits, milk and dairy products between the two groups. CONCLUSION: In addition to the local highland barley(zanba), most people also chose to purchase rice and flour, which changed the situation of single staple food in the past. However, compared with the healthy population in the disease area, the consumption rate and intake frequency of fish, shrimp and crabs, poultry and livestock viscera, eggs(fresh eggs) and vegetables(tomatoes, scallions, ginger and garlic) in KBD patients were significantly lower, the selection of meat varieties is single, mainly local yak meat, and the overall dietary structure still presents the risk of single type and unbalanced diet.

Competitive Redox Chemistries in Vanadium Niobium Oxide for Ultrafast and Durable Lithium Storage.

Niobium pentoxide (Nb2O5) anodes have gained increasing attentions for high-power lithium-ion batteries owing to the outstanding rate capability and high safety. However, Nb2O5 anode suffers poor cycle stability even after modified and the unrevealed mechanisms have restricted the practical applications. Herein, the over-reduction of Nb5+ has been demonstrated to be the critical reason for the capacity loss for the first time. Besides, an effective competitive redox strategy has been developed to solve the rapid capacity decay of Nb2O5, which can be achieved by the incorporation of vanadium to form a new rutile VNbO4 anode. The highly reversible V3+/V2+ redox couple in VNbO4 can effectively inhibit the over-reduction of Nb5+. Besides, the electron migration from V3+ to Nb5+ can greatly increase the intrinsic electronic conductivity for VNbO4. As a result, VNbO4 anode delivers a high capacity of 206.1 mAh g-1 at 0.1 A g-1, as well as remarkable cycle performance with a retention of 93.4% after 2000 cycles at 1.0 A g-1. In addition, the assembled lithium-ion capacitor demonstrates a high energy density of 44 Wh kg-1 at 5.8 kW kg-1. In summary, our work provides a new insight into the design of ultra-fast and durable anodes.

Visualization and bibliometric analysis of 3D printing in cartilage regeneration.

The self-repair ability of cartilage defects is limited, and 3D printing technology provides hope for the repair and regeneration of cartilage defects. Although 3D printing technology and cartilage repair and regeneration have been studied for decades, there are still few articles specifically describing the relationship between 3D printing and cartilage defect repair and regeneration, and a bibliometric analysis has not been completed. To supplement, sort out and summarize the content in related fields, we analyzed the research status of 3D printing technology and cartilage repair and regeneration from 2002 to 2022. According to the set search strategy, the Web of Science Core Collection was used as the data source, and the literature search was completed on December 6, 2022. CiteSpace V and VOSviewer were used as bibliometric tools to complete the analysis of the research focus and direction of the published literature. Based on the analysis results, we focus on the occurrence and development of this field of combined medical and engineering research. Moreover, the current advantages and limitations of this field as well as future development prospects are discussed in depth. It will help to shape researchers' understanding of 3D printing and cartilage repair and regeneration, inspire researchers' research ideas, guide research directions, and promote related research results to clinical application.

Preference of musculoskeletal pain treatment in middle-aged and elderly chinese people: a machine learning analysis of the China health and retirement longitudinal study.

BACKGROUND: Musculoskeletal pain is a major cause of physical disability, associated with huge socioeconomic burden. Patient preference for treatment is an important factor contributing to the choice of treatment strategies. However, effective measurements for evaluating the ongoing management of musculoskeletal pain are lacking. To help improve clinical decision making, it's important to estimate the current state of musculoskeletal pain management and analyze the contribution of patient treatment preference. METHODS: A nationally representative sample for the Chinese population was derived from the China Health and Retirement Longitudinal Study (CHARLS). Information on the patients' demographic characteristics, socioeconomic status, other health-related behavior, as well as history on musculoskeletal pain and treatment data were obtained. The data was used to estimate the status of musculoskeletal pain treatment in China in the year 2018. Univariate analysis and multivariate analysis were used to find the effect factors of treatment preference. XGBoost model and Shapley Additive exPlanations (SHAP) method were performed to analyze the contribution of each variable to different treatment preferences. RESULTS: Among 18,814 respondents, 10,346 respondents suffered from musculoskeletal pain. Approximately 50% of musculoskeletal pain patients preferred modern medicine, while about 20% chose traditional Chinese medicine and another 15% chose acupuncture or massage therapy. Differing preferences for musculoskeletal pain treatment was related to the respondents' gender, age, place of residence, education level, insurance status, and health-related behavior such as smoking and drinking. Compared with upper or lower limb pain, neck pain and lower back pain were more likely to make respondents choose massage therapy (P < 0.05). A greater number of pain sites was associated with an increasing preference for respondents to seek medical care for musculoskeletal pain (P < 0.05), while different pain sites did not affect treatment preference. CONCLUSION: Factors including gender, age, socioeconomic status, and health-related behavior may have potential effects on people' s choice of treatment for musculoskeletal pain. The information derived from this study may be useful for helping to inform clinical decisions for orthopedic surgeons when devising treatment strategies for musculoskeletal pain.

Research landscape of 3D printing in bone regeneration and bone repair: A bibliometric and visualized analysis from 2012 to 2022.

Three-dimensional printing (3DP) is a popular manufacturing technique with versatile potential for materials processing in tissue engineering and regenerative medicine. In particular, the repair and regeneration of significant bone defects remain as substantial clinical challenges that require biomaterial implants to maintain mechanical strength and porosity, which may be realized using 3DP. The rapid progress in 3DP development in the past decade warrants a bibliometric analysis to gain insights into its applications in bone tissue engineering (BTE). Here, we performed a comparative study using bibliometric methods for 3DP in bone repair and regeneration. A total of 2,025 articles were included, and the results showed an increase in the number of publications and relative research interest on 3DP annually worldwide. China was the leader in international cooperation in this field and also the largest contributor to the number of citations. The majority of articles in this field were published in the journal Biofabrication. Chen Y was the author who made the highest contribution to the included studies. The keywords included in the publications were mainly related to BTE and regenerative medicine (including "3DP techniques," "3DP materials," "bone regeneration strategies," and "bone disease therapeutics") for bone regeneration and repair. This bibliometric and visualized analysis provides significant insights into the historical development of 3DP in BTE from 2012 to 2022, which will be beneficial for scientists to conduct further investigations into this dynamic field.

A method for Kashin-Beck disease auxiliary diagnosis based on the features in regions of the potential lesion.

BACKGROUND: Kashin-Beck disease (KBD) is a severe arthropathy that causes deformity. Patients with advanced stages of KBD often show symptoms, such as short stature. Early-stage diagnosis and treatment can effectively prevent the disease from worsening. Diagnosis of early-stage patients is usually made by X-ray examination. However, the time-consuming image recognition and the lack of professional doctors may delay the patient's condition. Therefore, a method that can efficiently complete the auxiliary diagnosis is necessary. PURPOSE: This study presents a KBD auxiliary diagnosis method based on radiographs, which uses deep learning to locate potential lesion regions and extract features for accurate diagnosis. METHODS: This work presents a method that relies on hand radiographs to locate eight regions of the potential lesion (RoPL) and finally make the KBD auxiliary diagnosis. The localization of RoPL is achieved through a two-step model, with the first step predicting a rough location and a deep convolutional neural network (DCNN) with attention mechanism used to generate precise center coordinates based on the previous step's results. Based on the localization result, regional features are extracted, which provides information about the joints and textures of RoPL from a finer granularity. Another DCNN is utilized to obtain general features from hand radiographs, which provide morphological and structural information about the entire hand bone These features offer a concatenated feature for categorization to raise accuracy. A doctor-like approach is adopted to diagnose based on regional features to enhance performance, and a final decision is made using a vote that considers diagnostic outcomes from all aspects. The dataset used in our study was collected by our research team in KBD-endemic areas of Tibet since 2017, containing 373 diseased and 764 normal images. RESULT: Our model guarantees that over 95% of the predicted coordinates are within five pixels of the real coordinates according to Euclidean distance. The accuracy of the diagnostic network achieved 91.3%, with precision and recall achieving 83% and 87%, respectively. Compared to the approach without exact localization of the illness region on the same test set, our method achieved a roughly 6% increase in accuracy and nearly 30% increase in recall rate. CONCLUSIONS: Based on hand radiographs, this study suggests a novel method for KBD diagnosis. The high-precision localization network guarantees precise extraction of lesion-prone regional features, and the multi-scale features and innovative classification method further enhance model performance compared to related approaches.

In situ self-assembled organoid for osteochondral tissue regeneration with dual functional units.

The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial, directional and controllable differentiation of mesenchymal stem cells (MSCs) into cartilage and bone compartments. Emerging organoid technology offers new opportunities for osteochondral regeneration. In this study, we developed gelatin-based microcryogels customized using hyaluronic acid (HA) and hydroxyapatite (HYP), respectively for inducing cartilage and bone regeneration (denoted as CH-Microcryogels and OS-Microcryogels) through in vivo self-assembly into osteochondral organoids. The customized microcryogels showed good cytocompatibility and induced chondrogenic and osteogenic differentiation of MSCs, while also demonstrating the ability to self-assemble into osteochondral organoids with no delamination in the biphasic cartilage-bone structure. Analysis by mRNA-seq showed that CH-Microcryogels promoted chondrogenic differentiation and inhibited inflammation, while OS-Microcryogels facilitated osteogenic differentiation and suppressed the immune response, by regulating specific signaling pathways. Finally, the in vivo engraftment of pre-differentiated customized microcryogels into canine osteochondral defects resulted in the spontaneous assembly of an osteochondral unit, inducing simultaneous regeneration of both articular cartilage and subchondral bone. In conclusion, this novel approach for generating self-assembling osteochondral organoids utilizing tailor-made microcryogels presents a highly promising avenue for advancing the field of tissue engineering.

Constrained Condylar Prostheses for the Treatment of Charcot Arthropathy: A Case Report and Literature Review.

BACKGROUND: Neuroarthropathy of the knee or Charcot knee, leading to chronic joint destruction, is a rare disease that is difficult to diagnose. The treatment of this condition is difficult and controversial. CASE PRESENTATION: A 74-year-old Asian woman has had bilateral knee pain for 22 years and deformity for 10 years, which has been aggravating for 2 months. Physical examination showed bilateral knee varus deformity greater than 15°, and -20 to 90° range of motion. X-ray revealed bilateral varus deformity with massive free body hyperplasia. Combined with medical history as syringomyelia, the patient was diagnosed with bilateral Charcot knees and bilateral joint replacements were performed using Legacy Constrained Condylar Knee prostheses (LCCK; Zimmer, USA). The patient reported satisfactory treatment outcomes, pain relief, and improved range of motion in both knees, without postoperative complications or prosthesis loosening at 2 year after operation. CONCLUSIONS: Total knee arthroplasty (TKA) may be considered a viable option for treating the Charcot knee. The use of constrained condylar prostheses can produce satisfactory results. Attention should be given to survival risks, complications, and other potential determining factors associated with TKA when devising a treatment strategy for the Charcot knee.

Bibliometric and visualization analysis of stem cell therapy for meniscal regeneration from 2012 to 2022.

Background: Meniscus injuries, a common joint disease caused by long-term wear, trauma and inflammation, usually cause chronic dysfunction and pain in the joint. Current clinical surgeries mainly aim to remove the diseased tissue to alleviate patient suffering instead of helping with meniscus regeneration. As an emerging treatment, stem cell therapy has been verified to facilitate meniscus regeneration effectively. The purpose of this study is to investigate the publication conditions of stem cell therapy for meniscal regeneration and to visualize the research trends and frontiers. Methods: Relevant publications relevant to stem cells for meniscal regeneration was retrieved SCI-Expanded of the Web of Science database from 2012 to 2022. Research trends in the field were analysed and visualized by CiteSpace and VOSviewer. Results: A total of 354 publications were collected and analysed. The United States contributed the largest number of publications (118, 34.104%). Tokyo Medical Dental University has contributed the largest number of publications (34) among all full-time institutions. Stem cell research therapy has published the largest number of researches on stem cells for meniscal regeneration (17). SEKIYA. I contributed the majority of publications in this field (31), while Horie, M was the most frequently cited authors (166). #1 tissue engineering, #2 articular cartilage, #3 anterior cruciate ligament, #4 regenerative medicine, #5 scaffold are the chief keywords. This indicates that the current research hotspot has been transformed from basic surgical research to tissue engineering. Conclusion: Stem cell therapy is a promising therapeutic method for meniscus regeneration. This is the first visualized and bibliometric study to thoroughly construct the development trends and knowledge structure in the research field of stem cell therapy for meniscal regeneration in the past 10 years. The results thoroughly summarize and visualize the research frontiers, which will shed light on the research direction of stem cell therapy for meniscal regeneration.

Identification of the joint line in revision total knee arthroplasty using a multiple linear regression model: a cadaveric study.

INTRODUCTION: The results of revision total knee arthroplasty (rTKA) may be compromised by excessive joint line (JL) elevation. It is critical but challenging in reestablishing the JL in rTKA. Previous studies have confirmed that, biomechanically and clinically, JL elevation should not exceed 4 mm. Image-based studies described several approaches to locate the JL intraoperatively, however magnification errors could occur. In this cadaveric study, we aim to define an accurate and reliable method to determine the JL. MATERIALS AND METHODS: Thirteen male and eleven female cadavers were used, with an average age of death being 48.3 years. The transepicondylar width (TEW), the distance from the medial (MEJL) and lateral (LEJL) epicondyle, adductor tubercle (ATJL), fibular head (FHJL) and tibial tubercle (TTJL) to the JL were measured in 48 knees. Intra- and interobserver reliability and validity were tested prior to any additional analysis. Pearson correlation and linear regression analysis were used to examine the correlations between landmark-JL distances (LEJL, MEJL, ATJL, FHJL and TTJL) and the TEW, and to further derive models for intraoperative JL determination. The accuracy of different models, quantified by errors between estimated and measured landmark-JL distances, was compared using the Friedman and post hoc Dunn tests. RESULTS: The intra- and inter-observer measurements for TEW, MEJL, LEJL, ATJL, TTJL and FHJL did not differ significantly (p > 0.05). Between genders, significant differences were found on TEW, MEJL, LEJL, ATJL, FHJL and TTJL (p < 0.05). There was no association between TEW and either FHJL or TTJL (p > 0.05), while ATJL, MEJL, and LEJL were found to be correlated with TEW (p < 0.05). Six models were derived: (1) MEJL = 0.37*TEW (r = 0.384), (2) LEJL = 0.28*TEW (r = 0.380), (3) ATJL = 0.47*TEW (r = 0.608), (4) MEJL = 0.413*TEW - 4.197 (R2 = 0.473), (5) LEJL = 0.236*TEW + 3.373 (R2 = 0.326), (6) ATJL = 0.455*TEW + 1.440 (R2 = 0.556). Errors were defined as deviations between estimated and actual landmark-JL distances. The mean absolute value of the errors, created by Model 1-6 was 3.18 ± 2.25, 2.53 ± 2.15, 2.64 ± 2.2, 1.85 ± 1.61, 1.60 ± 1.59 and 1.71 ± 1.5, respectively. The error could be limited to 4 mm in 72.9%, 83.3%, 72.9%, 87.5%, 87.5%, and 93.8% of the cases by referencing Model 1-6, respectively. CONCLUSION: Compared to previous image-based measurements, the current cadaveric study most closely resembles a realistic view of intraoperative settings and could circumvents magnification errors. We recommend using Model 6, the JL can be best estimated by referencing the AT and the ATJL can be calculated as ATJL (mm) = 0.455*TEW (mm) + 1.440 (mm).

Exploring the Mechanism of Microfracture in the Treatment of Porcine Full-Thickness Cartilage Defect.

BACKGROUND: Microfracture has the most extensive clinical application because of its advantages of a single operation, unified process, and low operation cost. Because research on the repair mechanism of microfractures in the treatment of cartilage defects is not in-depth, this study aimed to elucidate the mechanism. PURPOSE: To identify the characteristic cell subsets at different repair stages after microfracture, systematically analyze the repair process of the defect area after microfracture, and investigate the mechanism of fibrocartilage repair. STUDY DESIGN: Descriptive laboratory study. METHODS: Full-thickness articular cartilage defects and microfractures was established in the right knee of Bama miniature pigs. Single-cell transcriptional assays were used to identify the characteristics of cells isolated from healthy articular cartilage and regenerated tissues. RESULTS: Microfractures induced mature fibrous repair in the full-thickness cartilage defect six months after surgery, while early stages of repair occurred within six weeks. Based on single-cell sequencing results, eight subsets and specific marker genes were identified. Two processes may occur after microfracture: normal hyaline cartilage regeneration and abnormal fibrocartilage repair. Regulatory chondrocytes, proliferative chondrocytes and cartilage progenitor cells (CPCs) may play important roles in the normal regeneration process. During abnormal repair, CPCs and skeletal stem cells may have different functions, and macrophages and endothelial cells may play important regulatory roles in the formation of fibrochondrocytes. CONCLUSIONS: Using single-cell transcriptome sequencing, this study investigated the tissue regeneration process and identified key cell subsets after microfracture. CLINICAL RELEVANCE: These results provide future targets for optimizing the repair effect of microfracture.

Multidisciplinary Guidelines for the Rational Use of Topical Non-Steroidal Anti-Inflammatory Drugs for Musculoskeletal Pain (2022).

(1) Background: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are one of the primary drugs for treating musculoskeletal pain. However, there are currently no evidence-based recommendations about drug selection, drug administration, drug interactions, and use in special populations or other pharmacology-related content of such medications. To this end, the Chinese Pharmaceutical Association Hospital Pharmacy Professional Committee developed multidisciplinary guidelines on using topical NSAIDs to treat musculoskeletal pain. (2) Methods: The guidelines development process followed the World Health Organization guideline development handbook, the GRADE methodology, and the statement of Reporting Items for Practice Guidelines in Healthcare. The guideline panel used the Delphi method to identify six clinical questions to be addressed in the guidelines. An independent systematic review team conducted a systematic search and integration of evidence. (3) Results: Based on the balance between the benefits and harms of an intervention, the quality of the evidence, patient preferences and values, and resource utilization, the guideline panel developed 11 recommendations and nine expert consensuses on using topical NSAIDs to treat acute and chronic musculoskeletal pain. (4) Conclusions: Based on the effectiveness and overall safety of topical NSAIDs, we recommend patients with musculoskeletal pain use topical NSAIDs and suggest high-risk patients use topical NSAIDs, such as those with other diseases or receiving other concurrent treatments. The evidenced-based guidelines on topical NSAIDs for musculoskeletal pain incorporated a pharmacist perspective. The guidelines have the potential to facilitate the rational use of topical NSAIDs. The guideline panel will monitor the relevant evidence and update the recommendations accordingly.

Influencing factors of weak grip strength and fall: a study based on the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: Fall is a major cause of mortality and cause a significant burden on the healthcare system and economic system. Weak grip strength signifies impaired function. Older people with weak grip strength are at a higher risk of death. China has the largest ageing population in the world today. This study aims to analyze the factors contributing to weak grip strength and fall among Chinese. METHODS: This study analyzed data from the 2011 baseline and 2015 follow-up survey of the China Health and Retirement Longitudinal Study (CHARLS). To identify the risk factors of fall and weak grip strength, we used a stepwise multivariable logistic regression model and a least absolute shrinkage and selection operator (LASSO) regression model. RESULTS: In the LASSO regression model, all the risk factors were not shrunken. In the stepwise logistic regression model, adjusted for gender, age, grip strength, depression, and chronic disease, we found that female (aOR = 1.376, 95% CI = 1.243-1.523; P < 0.001), history of ischemic stroke (aOR = 1.786, 95% CI = 1.263-2.524; P = 0.001), depression (aOR = 1.559, 95% CI = 1.396-1.742; P < 0.001), weak grip strength (aOR = 1.285, 95% CI = 1.105-1.494; P = 0.001), older age (aOR = 1.227, 95% CI = 1.163-1.294; P < 0.001), rheumatoid arthritis (aOR = 1.410, 95% CI = 1.270-1.560; P < 0.001), history of kidney disease (aOR = 1.383, 95% CI = 1.136-1.682; P = 0.001) were factors associated with fall significantly. After further adjusting, we found the risk factors of weak grip strength included symptomatic knee osteoarthritis (aOR = 1.755, 95% CI 1.158-2.661; P = 0.008), living in rural area (aOR = 2.056, 95% CI 1.290-3.277; P = 0.002), depression (aOR = 1.523, 95% CI 1.116-2.078; P = 0.008), older age (aOR = 2.116, 95% CI 1.801-2.486; P < 0.001). CONCLUSION: From the study, we found that older age and depression were risk factors of weak grip strength and fall. Weak grip strength was a risk factor of fall. Female, ischemic stroke, kidney disease, rheumatoid arthritis were risk factors of fall; living in rural area and symptomatic knee osteoarthritis were risk factors of weak grip strength.

Self-assembled microtissues loaded with osteogenic MSCs for in vivo bone regeneration.

Bone regeneration strategies based on mesenchymal stem cell (MSC) therapy have received widespread attention. Although MSC incorporation into bone scaffolds can help with the repair process, a large number of studies demonstrate variable effects of MSCs with some noting that the inclusion of MSCs does not provide better outcomes compared to unseeded scaffolds. This may in part be related to low cell survival following implantation and/or limited ability to continue with osteogenic differentiation for pre-differentiated cells. In this study, we incorporated MSCs into gelatin microcryogels to form microtissues, and subjected these microtissues to osteogenic induction. We then mixed as-formed microtissues with those subjected to 6 days of osteogenic induction in different ratios, and investigated their ability to induce in vitro and in vivo osteogenesis during self-assembly. Using a full-thickness rat calvarial defect model, we found that undifferentiated and osteogenically induced microtissues mixed in a ratio of 2:1 produced the best outcomes of bone regeneration. This provides a new, customizable cell-based therapeutic strategy for in vivo repair of bone defects.