State transition and intercellular communication of synovial fibroblasts in response to chronic and acute shoulder injuries unveiled by single-cell transcriptomic analyses.

PURPOSE: We aimed to investigate the heterogeneity of synovial fibroblasts and their potential to undergo cell state transitions at the resolution of single cells. MATERIALS AND METHODS: We employed the single-cell RNA sequencing (scRNA-seq) approach to comprehensively map the cellular landscape of the shoulder synovium in individuals with chronic rotator cuff tears (RCTs) and acute proximal humerus fractures (PHFs). Utilizing unbiased clustering analysis, we successfully identified distinct subpopulations of fibroblasts within the synovial environment. We utilized Monocle 3 to delineate the trajectory of synovial fibroblast state transition. And we used CellPhone DB v2.1.0 to predict cell-cell communication patterns within the synovial microenvironment. RESULTS: We identified eight main cell clusters in the shoulder synovium. Unbiased clustering analysis identified four synovial fibroblast subpopulations, with diverse biological functions associated with protein secretion, ECM remodeling, inflammation regulation and cell division. Lining, mesenchymal, pro-inflammatory and proliferative fibroblasts subsets were identified. Combining the results from StemID and characteristic gene features, mesenchymal fibroblasts exhibited characteristics of fibroblast progenitor cells. The trajectory of synovial fibroblast state transition showed a transition from mesenchymal to pro-inflammatory and lining phenotypes. In addition, the cross talk between fibroblast subclusters increased in degenerative shoulder diseases compared to acute trauma. CONCLUSION: We successfully generated the scRNA-seq transcriptomic atlas of the shoulder synovium, which provides a comprehensive understanding of the heterogeneity of synovial fibroblasts, their potential to undergo state transitions, and their intercellular communication in the context of chronic degenerative and acute traumatic shoulder diseases.

Biomechanical Properties of Bionic Collum Femoris Preserving Hip Prosthesis: A Finite Element Analysis.

OBJECTIVE: Compared with total hip replacement, conventional collum femoris preserving prosthesis has a better bone retention effect. However, damage to the trabecular bone of the proximal femur leads to inevitable abnormal stress distribution, which leads to increased risks of femoral neck bone absorption, periprosthetic fracture, prosthesis loosening, rotation, and sinking. Thus, we compare the biomechanical properties of collum femoris preserving (CFP) and bionic collum femoris preserving (BCFP) hip prostheses. METHODS: The Sawbone digital model (#3503, left, medium) was selected as the research object. We used the Mimics 21.0 software to reconstruct the digital model of the femur and the SolidWorks 2019 software to build and assemble the three-dimensional models of CFP and BCFP prostheses. With the ANSYS Workbench 2021R1 software, the models were meshed and assigned values to simulate the load of a single foot under slow walking. We measured the mechanical distribution of the whole model and obtained the stress nephogram. RESULTS: For CFP prosthesis, the peak stresses of the medial interface of the stem neck, the lateral interface of the stem neck, and the end of the stem were 64.894, 32.199, and 8.578 MPa, respectively; the peak stresses of the medial surface of the femoral shaft, the lateral surface of femoral shaft, the medial femoral neck bone-prosthesis interface (osteotomy interface), the lateral femoral neck bone-prosthesis interface (basal area), the lateral femoral neck bone-prosthesis interface (osteotomy interface), and the greater trochanter area were 28.093, 24.790, 14.388, 5.118, 4.179, and 8.245 MPa, respectively; the valley stress of the greater trochanter area was 1.134 MPa. For BCFP prosthesis, the peak stresses of the medial interface of the stem neck, the lateral interface of the stem neck, and the end of the stem were 47.015, 26.771, and 47.593 MPa, respectively; the peak stress of tension screw was 15.739 MPa; the peak stresses of the medial surface of the femoral shaft, the lateral surface of femoral shaft, the medial femoral neck bone-prosthesis interface (osteotomy interface), the lateral femoral neck bone-prosthesis interface (basal area), the lateral femoral neck bone-prosthesis interface (osteotomy interface) and the greater trochanter area were 28.581, 25.364, 15.624, 6.434, 4.986, and 8.796 MPa, respectively; the valley stress of the greater trochanter area was 1.419 MPa; the peak stress of bone-metal interface between the tension screw and the lateral surface of the femur was 5.858 MPa. CONCLUSION: Compared with the CFP prosthesis, the design of the BCFP prosthesis is based on the lever balance theory. With the bionic reconstruction of tension trabeculae, BCFP prosthesis makes up for the defects of CFP prosthesis design, optimizes the stress distribution, and reduces the stress shelter effect of the proximal femur, which has better biomechanical properties.

Bionic reconstruction of tension trabeculae in short-stem hip arthroplasty: a finite element analysis.

BACKGROUND: Short-stem hip arthroplasty (SHA) is characterized by metaphyseal load transfer that effectively preserves the bone stock, but still suffers from stress shielding in the proximal femur. We designed a tension screw to mimic tension trabeculae in the new bionic collum femoris preserving (BCFP) short stem for bionic reconstruction, aiming to restore the biomechanics of hip joint. METHODS: Native femur finite element model was constructed to investigate the biomechanics of hip joint based on computed tomography (CT) data. The maximum absolute principal stress/strain cloud chart allowed the direction of stress/strain to be assessed. Six BCFP models with different screw angles (5°, 10°, 15°, 20°, 25°, and 30°) and the Corail model were created. The stress/strain distribution and overall stiffness were compared between each of the BCFP and Corail implanted models. RESULTS: The native model visualized the transfer pathways of tensile and compressive stress. The BCFP stems showed significantly higher stress and strain distribution in the greater trochanteric region compared to conventional total hip arthroplasty (THA). In particular, the BCFP-5° stem demonstrated the highest average strain in both medial and lateral regions and the overall stiffness was closest to the intact femur. CONCLUSIONS: Stress transfer pathways of trabecular architecture provide biomechanical insight that serves as the basis for bionic reconstruction. The tension screw improves load transfer pattern in the proximal femur and prevents stress reduction in the greater trochanteric region. The BCFP-5° stem minimizes the stress shielding effect and presents a more bionic mechanical performance.

A Transosseous Suture as an Alternative to Suture Anchor on Anterior-Avulsion Greater Tuberosity Fragment Fixation in Neer Three-Part Proximal Humeral Fracture: A Biomechanical Study.

OBJECTIVE: Greater tuberosity (GT) fragments were communicated, and additional techniques to increase the GT fragment stability after the locking plate fixation was necessary. This study aimed to analyze the reinforcement effects on the anterior-avulsion GT fragment in Neer three-part proximal humeral fractures (PHFs) using transosseous suture and suture anchor techniques. METHODS: Eighteen fresh-frozen human cadaveric shoulder specimens were used in the study. Standardized fracture of the GT and surgical neck was created in 18 human cadaveric proximal humerus. The GT fragments were reinforced with transosseous suture (TS), suture anchor (SA), and suture in addition to the PHILOS plate fixation. The fixed humerus was tested by applying static loading to the supraspinatus tendon. Load forces and fragment displacement were evaluated by a biomechanical testing machine, and the load to 3- and 5-mm displacements, load to failure, and mode of failure were recorded for all specimens. Nonparametric variables were examined by the Kruskal-Wallis test, and the Bonferroni post hoc test was used to analyze the mean loads to create 3- and 5-mm displacements as well as the failure load. RESULTS: The age, female proportion, and bone mineral density showed no statistically significant differences between the three groups. The mean loading force to create 3-mm and 5-mm displacement in the TS group (254.9 ± 77.4, 309.6 ± 152.7) were significantly higher than those in the suture group (136.1 ± 16.7, 193.4 ± 14.5) (P = 0.024, P = 0.005). For the SA group, the force to create 3- and 5-mm displacement (204.3 ± 60.9, 307.8 ± 73.5) were comparable to those in the TS group (P = 0.236, P = 0.983). Moreover, the loading force to failure in the TS group (508.6 ± 217.7) and SA group (406.6 ± 114.9) was significantly higher than that in the suture group (265.9 ± 52.1) (P = 0.021, P = 0.024). In the TS group, three failed due to tendon-bone junction rupture; bone tunnel broken occurred in two specimens; suture rupture could also be seen in one specimen. All specimens in the suture group failed because of suture rupture. In the SA group, three specimens failed due to suture rupture; two failed secondary to tendon-bone junction rupture; and one failed because of shaft fracture. CONCLUSIONS: Transosseous suture is a new type of reinforcement for GT fragment in Neer-three part PHFs. The transosseous suture was superior to the suture only in the reinforcement of the anterior-avulsion GT fragment of Neer three-part PHFs, and it had comparable biomechanical strength to the suture anchor.

Fracture Line Morphology of Greater Tuberosity Fragments of Neer Three- and Four-Part Proximal Humerus Fractures.

OBJECTIVE: In complicated Neer three- and four-part proximal humerus fracture (PHF), greater tuberosity (GT) fragments are often comminuted, and the currently widely used locking plate may not fix GT fragments effectively. A further understanding of morphological characteristics of the GT fragments may help explore new fixation devices. This study aimed to determine the fracture line morphology of the GT fragment of Neer three- or four-part PHF and analyze the location relationship between the locking plate and the GT fragment. METHODS: Seventy-one three-dimensional computed tomography scans of Neer three- and four-part PHF were retrospectively reviewed between January 2014 and June 2019. Fracture fragments were reconstructed and virtually reduced in the Mimics software, and fracture lines of GT fragments were depicted on a humerus template in the 3-matic software and then were superimposed altogether. The common sites of the GT fracture were identified, and the location relationship between the locking plate and GT fragments was analyzed in a computer-simulated scenario. RESULTS: The fracture line morphology of GT fragments was similar between Neer three- and four-part PHF. The overall morphology of GT fragments was in a fan shape, which could be summarized as anterior, superior, posterior, and middle lines. Of these, we identified 51 split and 29 avulsion type GT fragments based on the Mutch classification, and they could occur simultaneously in a PHF. The overall morphology of split type fragments was in a fan shape, and avulsion type fragments showed a quite distinguishable distribution pattern. A GT fragment could be classified as anterior-split, posterior-split, complete-split, anterior -avulsion, and posterior-avulsion type based on its morphology and location. The median percentage of fragment area covered by the plate was 32.3% in all of the fragments, and it was 69.4%, 23.0%, 37.2%, 21.8%, 0.0% in anterior-split, posterior-split, complete-split, anterior-avulsion, and posterior-avulsion type GT fragments. We defined the posterior-split, anterior-avulsion, and posterior-avulsion type GT fragments as the risky GT fragments, and they occurred in 43 (60.6%) Neer three- and four-part PHFs. CONCLUSION: The fracture line morphology of GT fragments of Neer three- and four-part PHF was in a fan shape. GT fragments could be classified based on their location and morphology. The extent of GT fragment coverage provided by the locking plate differed in various fragment types, and we identified the anterior-avulsion, posterior-avulsion, and posterior-split type fragments as the risky GT fragments with a high incidence rate in Neer three- and four-part PHFs.

Tuberosity reconstruction baseplate for shoulder hemiarthroplasty: Morphological design and biomaterial application.

Background: Shoulder hemiarthroplasty is prone to tuberosity malposition and migration, reducing the rate of tuberosity healing. We proposed to design a tuberosity reconstruction baseplate to assist in tuberosity integration and to evaluate the mechanical properties of baseplate made from the novel biomaterial carbon fiber reinforced polymer (CFRP) composites. Methods: The three-dimensional model of native proximal humerus was constructed by computed tomography (CT) data. The morphological design of baseplate was based on the tuberosity contour and rotator cuff footprint. Finite element models were created for different thicknesses of CFRP composites, poly (ether-ether-ketone) (PEEK) and titanium-nickel (TiNi) alloy. The permissible load and suture hole displacements were applied to evaluate the mechanical properties. Results: The structurally optimized model made of CFRP composites provided superior strength and deformability, compared to the PEEK material and TiNi alloy. Its permissible load was above 200 N and the suture hole displacement was between 0.9 and 1.4 mm. Conclusion: This study proposed a method for designing tuberosity reconstruction baseplate based on morphological data and extended the application of biomaterial CFRP composites in orthopedics field. The optimized model made of CFRP composites allowed a certain extent of elastic deformation and showed the possibility for dynamic compression of tuberosity bone blocks.

Application of Hybrid Electrically Conductive Hydrogels Promotes Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) occurs frequently, and the prognosis is unsatisfactory. As the gold standard of treatment, autologous nerve grafting has several disadvantages, such as lack of donors and complications. The use of functional biomaterials to simulate the natural microenvironment of the nervous system and the combination of different biomaterials are considered to be encouraging alternative methods for effective tissue regeneration and functional restoration of injured nerves. Considering the inherent presence of an electric field in the nervous system, electrically conductive biomaterials have been used to promote nerve regeneration. Due to their singular physical properties, hydrogels can provide a three-dimensional hydrated network that can be integrated into diverse sizes and shapes and stimulate the natural functions of nerve tissue. Therefore, conductive hydrogels have become the most effective biological material to simulate human nervous tissue's biological and electrical characteristics. The principal merits of conductive hydrogels include their physical properties and their electrical peculiarities sufficient to effectively transmit electrical signals to cells. This review summarizes the recent applications of conductive hydrogels to enhance peripheral nerve regeneration.

Short-term effect of ambient air pollutant change on the risk of tuberculosis outpatient visits: a time-series study in Fuyang, China.

There is growing evidence that air pollution plays a role in TB, and most studies have been conducted in the core countries with inconsistent results. Few studies have comprehensively included the six common air pollutants, so they cannot consider whether various pollutants interact with each other. Our objectives were to investigate the association between short-term exposure to six common air pollutants and the risk of tuberculosis outpatient visits in Fuyang, China, 2015-2020. We combined the two models to explore the effects of exposure to six air pollutants on the risk of tuberculosis outpatient visits, including the Poisson generalized linear regression model and distributed lag non-linear model (DLNM). We performed stratified analyses for the season, type of cases, gender, and age. We used the lag-specific relative risks and cumulative relative risk obtained by increasing pollutant concentration by per 10 units to evaluate the connection between six air pollutants and TB; PM2.5 (RR = 1.0018, 95% CI: 1.0004-1.0032, delay of 12 days) and SO2 (RR = 1.0169, 95% CI: 1.0007-1.0333, lag 0-16 days) were 0.9549 (95% CI: 0.9389-0.9712, lag 0 day) and 0.8212 (95% CI: 0.7351-0.9173, 0-20-day lag). Stratified analyses showed that seasonal differences had a greater impact on TB, males were more likely to develop TB than females, older people were more likely to develop TB than younger people, and air pollution had a great impact on new cases. Exposure to O3, CO, PM10, PM2.5, and NO2 increases the risk of TB outpatient visits, except SO2 which reduces the risk. The incidence of TB has seasonal fluctuations. It is necessary for the government to establish a sound environmental monitoring and early warning system to strengthen the monitoring and emission management of pollutants in the atmosphere. Management, prevention, and treatment measures should be developed for high-risk groups (males and older people), reducing the risk of TB by reducing their specific behaviors and changing their lifestyle. We need to pay more attention to the impact of seasonal effects on TB to protect TB patients and avoid a shortage of medical resources, and it is necessary for the government to develop some seasonal preventive measures in the future.

Chitin Nerve Conduits with Three-Dimensional Spheroids of Mesenchymal Stem Cells from SD Rats Promote Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) is an unresolved medical problem with limited therapeutic effects. Epineurium neurorrhaphy is an important method for treating PNI in clinical application, but it is accompanied by inevitable complications such as the misconnection of nerve fibers and neuroma formation. Conduits small gap tubulization has been proved to be an effective suture method to replace the epineurium neurorrhaphy. In this study, we demonstrated a method for constructing peripheral nerve conduits based on the principle of chitosan acetylation. In addition, the micromorphology, mechanical properties and biocompatibility of the chitin nerve conduits formed by chitosan acetylation were further tested. The results showed chitin was a high-quality biological material for constructing nerve conduits. Previous reports have demonstrated that mesenchymal stem cells culture as spheroids can improve the therapeutic potential. In the present study, we used a hanging drop protocol to prepare bone marrow mesenchymal stem cell (BMSCs) spheroids. Meanwhile, spherical stem cells could express higher stemness-related genes. In the PNI rat model with small gap tubulization, BMSCs spheres exhibited a higher ability to improve sciatic nerve regeneration than BMSCs suspension. Chitin nerve conduits with BMSCs spheroids provide a promising therapy option for peripheral nerve regeneration.

XT-type DNA hydrogels loaded with VEGF and NGF promote peripheral nerve regeneration via a biphasic release profile.

Peripheral nerve injury (PNI) remains an unresolved challenge in the medicine area. With the development of biomaterial science and tissue engineering, a variety of nerve conduits were widely applied for repairing long defect PNI. DNA materials are developing rapidly due to their multiple advantages. In the present study, we aim to combine a DNA hydrogel, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) to construct a new type of delivery system, which could achieve a biphasic release profile of VEGF and NGF by taking advantage of the different degradation rates between X- and T-type DNA. In vitro results showed that the DNA gel + VEGF/NGF system could promote proliferation, migration and myelination of Rat Schwann cells (RSC) while maintaining cell viability. In vivo results indicated a better effect of DNA gel + VEGF/NGF on promoting repair of long defect PNI than the hollow chitin conduits (CT), DNA gel or VEGF/NGF group. The new technology invention holds promising clinical application prospects for repairing PNI and may be used broadly after step-by-step improvement.

Emergence of a young case infected with avian influenza A (H5N6) in Anhui Province, East China during the COVID-19 pandemic.

In the context of the coronavirus disease 2019 pandemic, we investigated the epidemiological and clinical characteristics of a young patient infected by avian influenza A (H5N6) virus in Anhui Province, East China, and analyzed genomic features of the pathogen in 2020. Through the cross-sectional investigation of external environment monitoring (December 29-31, 2020), 1909 samples were collected from Fuyang City. It was found that the positive rate of H5N6 was higher than other areas obviously in Tianma poultry market, where the case appeared. In addition, dual coinfections were detected with a 0.057% polymerase chain reaction positive rate the surveillance years. The virus was the clade 2.3.4.4, which was most likely formed by genetic reassortment between H5N6 and H9N2 viruses. This study found that the evolution rates of the hemagglutinin and neuraminidase genes of the virus were higher than those of common seasonal influenza viruses. The virus was still highly pathogenic to poultry and had a preference for avian receptor binding.

Lessons from an active surveillance pilot to assess the pneumonia of unknown etiology surveillance system in China, 2016: the need to increase clinician participation in the detection and reporting of emerging respiratory infectious diseases.

BACKGROUND: We sought to assess reporting in China's Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system's detection of respiratory infections of public health significance. METHODS: From February 29-May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. RESULTS: Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive. < 10% PUE case medical records documented whether or not there were exposures to animals or others with respiratory illness. Most commonly cited reasons for not reporting cases were no awareness of the PUE system (76%) and not understanding the case definition (53%). CONCLUSIONS: Most clinicians have limited awareness of and are not reporting to the PUE system. Exposures related to respiratory infections are rarely documented in medical records. Increasing clinicians' awareness of the PUE system and including relevant exposure items in standard medical records may increase reporting.

Circ_0136474 and MMP-13 suppressed cell proliferation by competitive binding to miR-127-5p in osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative joint disease whose pathogenesis remains unclear. The research aims to investigate the roles of Circ_0136474/miR-127-5p/MMP-13 axis in OA. Differentially expressed circRNAs and miRNAs in OA cartilage tissue were screened out and visualized by R project based on RNA-seq data and microarray data respectively. qRT-PCR was carried out for detection of relative expression levels of Circ_0136474, miR-127-5p, MMP-13 and other inflammatory factors and Western blot analysis was conducted to detect the protein expression level of MMP-13. CCK-8 assay and flow cytometry were conducted to determine cell proliferation and cell apoptotic ability respectively. RNA-fluorescence in situ hybridization (RNA-FISH) experiments were conducted to confirm the immune-localization of the Circ_0136474 and MMP-13 in human tissues. Targeted relationships were predicted by bioinformatic analysis and verified by dual-luciferase reporter assay. Our findings revealed that the expression levels of both Circ_0136474 and MMP-13 in OA cartilage tissue were significantly higher than that in normal cartilage tissue. Circ_0136474 could suppress cell proliferation by facilitating MMP-13 expression and suppressing miR-127-5p expression in OA. Overexpression of miR-127-5p negatively regulated MMP-13 expression to enhance cell proliferation. Our study demonstrated that Circ_0136474 and MMP-13 suppressed cell proliferation, while enhanced cell apoptosis by competitive binding to miR-127-5p in OA, which may well provide us with a new therapeutic strategy for osteoarthritis.

Glucocorticoid and pyrazolone treatment of acute fever is a risk factor for critical and life-threatening human enterovirus 71 infection during an outbreak in China, 2008.

BACKGROUND: Human enterovirus 71 (HEV71) causes outbreaks of life-threatening diseases throughout the world. The genesis of these severe diseases is unknown. METHODS: During an outbreak of HEV71 infection, we investigated risk factors for critical illness. We developed a modified pediatric index of mortality (mPIM) incorporating heart rate, temperature, white blood cell count, respiratory rate, chest infiltrates, skin color, reflexes, responsiveness, and mobility. We calculated the mPIM for 103 patients (22 deaths) using complete scoring criteria in the medical record. In a case-control study, we compared cases (mPIM > or =10 or death) with controls (mPIM = 0-9) by drugs received within 96 hours after onset of fever, initial temperature, age, and nutritional anthropometry. RESULTS: About 66% (68/103) of the patients with an mPIM score (28 cases and 40 controls) had data on initial exposures. About 50% of the 28 cases and 18% of the 40 controls received an injection to treat fever during the first 96 hours after onset (Odds ratio [OR] = 7.0, 95% confidence interval [CI]: 1.8-28). Injections containing exclusively glucocorticoids (OR = 4.8, 95% CI: 1.2-21) or pyrazolones (OR = 4.1, 95% CI: 0.91-19, P = 0.047) were risk factors for severe HEV71 infection. About 25% of cases and 5% of controls received both drugs parenterally while 7% of cases and 30% of controls received neither (OR = 21, 95% CI: 1.8-305). Conversely, cases and controls had identical average initial temperature, and did not differ significantly by age, sex, nutritional measurements, use of other drugs, or timeliness of medical care received. CONCLUSION: Fever treatment with glucocorticoids and/or pyrazolones is a risk factor for life-threatening HEV71 infection.