Transdermal buprenorphine patch as an adjunct to multimodal analgesia after total joint arthroplasty: a retrospective cohort study.

Background: Total hip arthroplasty or total knee arthroplasty (THA/TKA) is often associated with varying degrees of pain. In recent years, transdermal buprenorphine (TDB) patch has shown encouraging results for acute postoperative pain control in orthopedic surgery. The aim of our study was to investigate the efficacy and safety of the combination of TDB patch and nonsteroidal anti-inflammatory drugs (NSAIDs) as a multimodal analgesic regimen after THA/TKA. Methods: Patients who underwent THA and TKA between January 2022 and January 2023 were reviewed. Three postoperative analgesic regimens were selected: Group A (flurbiprofen 50 mg and tramadol 37.5 mg/acetaminophen 325 mg), Group B (flurbiprofen 50 mg and TDB 5 mg), and Group C (Parecoxib 40 mg and TDB 5 mg). The primary outcomes were the Wong-Baker face pain scale revision (FPS-R) scores and the rate of sleep disturbances. Secondary outcomes of the study included the proportion of patients with postoperative pain relief rates categorized as 0%, <50%, ≥50%, and 100%. Results: The dynamic FPS-R pain scores on day 3 after surgery in Group B were significantly lower than those in Group A for THA (P < 0.017). The dynamic FPS-R pain scores were lowest in Group C on day 2 and 3 after THA and TKA (P < 0.017). Rate of sleep disturbances was significantly lower in Group B for THA and in Group C for TKA, respectively, compared with that in Group A (P < 0.017). The proportion of dynamic pain relief rate ≥50% in Group C was statistically higher than that in Group A for THA (P < 0.017). Rate of adverse reactions among three groups for THA and TKA was not statistically different (P > 0.05). Conclusion: This study suggests that the combination of TDB patch and NSAIDs is safe and effective for postoperative analgesia after THA/TKA.

[Transverse small incision intrathecal "loop" minimally invasive suture for treatment of acute Achilles tendon rupture].

Objective: To evaluate the effectiveness and feasibility of a transverse small incision intrathecal "loop" minimally invasive suture for acute Achilles tendon rupture. Methods: The clinical data of 30 patients with acute Achilles tendon rupture treated with transverse small incision intrathecal "loop" minimally invasive suture between January 2022 and October 2023 was retrospectively analyzed. The patients were all male, aged from 29 to 51 years, with an average of 39.8 years. The cause of injury was acute sports injury, and the time from injury to operation was 1-14 days, with an average of 3.4 days. The operation time, incision length, intraoperative blood loss, intraoperative complications, wound healing, and hospital stay were recorded. Postoperative appearance and function of ankle were evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Vancouver Scar Scale (VSS) score, and Arner-Lindholm score. Results: The operation time ranged from 30 to 90 minutes, with an average of 54.2 minutes; the incision length ranged from 1.3 to 3.5 cm, with an average of 2.2 cm; the intraoperative blood loss ranged from 5 to 70 mL, with an average of 22.3 mL; and the hospital stay ranged from 2 to 6 days, with an average of 3.7 days. All incisions healed by first intention, and there was no incision infection, poor healing, and deep venous thrombosis. All patients were followed up 5.3-22.0 months (mean, 14.7 months). During the follow-up, all the 30 patients had returned to exercise, and there was no complication such as Achilles tendon re-rupture, postoperative infection, and gastrocnemius muscle injury. At last follow-up, the AOFAS ankle-hindfoot score was 82-100, with an average of 95.1; the VSS score was 1-4, with an average of 2.1; according to the Arner-Lindholm score, 24 cases were rated as excellent and 6 cases as good. Conclusion: Transverse small incision intrathecal "loop" minimally invasive suture for the treatment of acute Achilles tendon rupture has the advantages of simple instrument, convenient operation, small trauma, quick recovery, and satisfactory effectiveness.

Simple "Door-Locking" Technique Using One Single-Row Anchor for Repairing Large Bony Bankart Lesions.

Large bony Bankart injuries are typically stabilized using screws or plates or multiple anchors. Here, the "door-locking" technique, using a single-row anchor, can provide effective fixation for massive bony Bankart injuries. This technique offers several advantages over open fixation surgery or other techniques that use more than 2 suture anchors, including simpler surgical procedures, lower medical costs, and satisfactory clinical outcomes.

The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Osteocyte-derived sclerostin impairs cognitive function during ageing and Alzheimer's disease progression.

Ageing increases susceptibility to neurodegenerative disorders, such as Alzheimer's disease (AD). Serum levels of sclerostin, an osteocyte-derived Wnt-ß-catenin signalling antagonist, increase with age and inhibit osteoblastogenesis. As Wnt-ß-catenin signalling acts as a protective mechanism for memory, we hypothesize that osteocyte-derived sclerostin can impact cognitive function under pathological conditions. Here we show that osteocyte-derived sclerostin can cross the blood-brain barrier of old mice, where it can dysregulate Wnt-ß-catenin signalling. Gain-of-function and loss-of-function experiments show that abnormally elevated osteocyte-derived sclerostin impairs synaptic plasticity and memory in old mice of both sexes. Mechanistically, sclerostin increases amyloid ß (Aß) production through ß-catenin-ß-secretase 1 (BACE1) signalling, indicating a functional role for sclerostin in AD. Accordingly, high sclerostin levels in patients with AD of both sexes are associated with severe cognitive impairment, which is in line with the acceleration of Αß production in an AD mouse model with bone-specific overexpression of sclerostin. Thus, we demonstrate osteocyte-derived sclerostin-mediated bone-brain crosstalk, which could serve as a target for developing therapeutic interventions against AD.

Elimination of Senescent Osteocytes by Bone-Targeting Delivery of ß-Galactose-Modified Maytansinoid Prevents Age-Related Bone Loss.

The accumulation of senescent cells in bone during aging contributes to senile osteoporosis, and clearance of senescent cells by senolytics could effectively alleviate bone loss. However, the applications of senolytics are limited due to their potential toxicities. Herein, small extracellular vesicles (sEVs) have been modified by incorporating bone-targeting peptide, specifically (AspSerSer)6, to encapsulate galactose-modified Maytansinoids (DM1). These modified vesicles are referred to as (AspSerSer)6-sEVs/DM1-Gal, and they have been designed to specifically clear the senescent osteocytes in bone tissue. In addition, the elevated activity of lysosomal ß-galactosidase in senescent osteocytes, but not normal cells in bone tissue, could break down DM1-Gal to release free DM1 for selective elimination of senescent osteocytes. Mechanically, DM1 could disrupt tubulin polymerization, subsequently inducing senescent osteocytes apoptosis. Further, administration of bone-targeting senolytics to aged mice could alleviate aged-related bone loss without non-obvious toxicity. Overall, this bone-targeting senolytics could act as a novel candidate for specific clearance of senescent osteocytes, ameliorating age-related bone loss, with a promising therapeutic potential for senile osteoporosis.

[Effectiveness analysis of "tail compression fixation+suture bridge" technology under shoulder arthroscopy for treating primary tear in medial enthesis of rotator cuff].

Objective: To investigate the feasibility and effectiveness of "tail compression fixation+suture bridge" technology under shoulder arthroscopy for treating primary tear in medial enthesis of rotator cuff. Methods: The clinical data of 11 patients with primary tear in medial enthesis of rotator cuff who met the selection criteria between October 2020 and October 2022 were retrospectively analyzed, including 3 males and 8 females, aged 39-79 years, with an average of 61.0 years. Rotator cuff injury was caused by traumatic fall in 8 cases, and the time from injury to admission was 1-4 months, with an average of 2.0 months; the remaining 3 cases had no obvious inducement. The active range of motion of the affected shoulder was limited, with an active forward flexion range of motion of (64.1±10.9)°, abduction of (78.1±6.4)°, internal rotation of (48.2±6.6)°, and external rotation of (41.8±10.5)°; 5 cases had shoulder stiffness. The preoperative visual analogue scale (VAS) score was 7.8±0.8 and the American Society of Shoulder and Elbow Surgeons (ASES) score was 23.9±6.4. The patients were treated with "tail compression fixation+suture bridge" technology under shoulder arthroscopy, and the pain and functional recovery were evaluated by VAS score, ASES score, and active range of motion of shoulder joint at last follow-up; MRI was performed after operation, and the integrity of rotator cuff was evaluated by Sugaya classification system. Results: All the 11 patients were followed up 2-22 months, with an average of 13.5 months. All incisions healed by first intention, and there was no complication such as infection, rotator cuff re-tear, and anchor falling off. At last follow-up, the VAS score was 0.8±0.7 and the ASES score was 93.5±4.2, which significantly improved when compared with those before operation ( P<0.05). All 11 patients had no significant swelling in the shoulders, and the active range of motion was (165.1±8.8)° in flexion, (75.3±8.4)° in abduction, (56.6±5.5)° in internal rotation, and (51.8±4.0)° in external rotation, which significantly improved when compared with those before operation ( P<0.05). Shoulder MRI showed adequate tendon thickness and good continuity in 9 cases, including 4 cases with partial high signal area; and 2 cases with inadequate tendon thickness but high continuity and partial high signal area. According to Sugaya classification system, there were 4 cases of type 1 (36.4%), 5 cases of type 2 (45.5%), and 2 cases of type 3 (18.1%). Conclusion: For the patients with primary tear in medial enthesis of rotator cuff, the "tail compression fixation+suture bridge" technology under shoulder arthroscopy is simple and effective.

Glucose-Responsive Antioxidant Hydrogel Accelerates Diabetic Wound Healing.

Diabetic complications can be ameliorated by inhibiting excessive oxidative stress with antioxidants. To enhance therapeutic intervention, it is crucial to develop intelligent scaffolds for efficient delivery of antioxidants to diabetic wounds. This study introduces reversible boronic bonds to create an intelligent antioxidant hydrogel scaffold. This study modifies gelatin methacryloyl (GelMA) with 4-carboxyphenyboronic acid (CPBA) to synthesize a derivative of GelMA (GelMA-CPBA), and then photo cross-links GelMA-CPBA with (-)-epigallocatechin-3-gallate (EGCG) to form GelMA-CPBA/EGCG (GMPE) hydrogel. The GMPE hydrogel responds to changes in glucose levels, and more EGCG is released as glucose level increases due to the dissociation of boronic ester bonds. The GMPE hydrogel shows good biocompatibility and biodegradability, and its mechanical property is similar to that of the skin tissue. Both in vitro and in vivo results demonstrate that the GMPE hydrogel scaffolds effectively eliminate reactive oxygen species (ROS), reduce the inflammation, and promote angiogenesis, thereby improve collagen deposition and tissue remodeling during diabetic wound healing. This strategy offers new insight into glucose-responsive scaffolds, and this responsive antioxidan hydrogel scaffold holds great potential for the treatment of chronic diabetic wounds.

Atrophic skeletal muscle fibre-derived small extracellular vesicle miR-690 inhibits satellite cell differentiation during ageing.

BACKGROUND: Sarcopenia is a common and progressive skeletal muscle disorder characterized by atrophic muscle fibres and contractile dysfunction. Accumulating evidence shows that the number and function of satellite cells (SCs) decline and become impaired during ageing, which may contribute to impaired regenerative capacity. A series of myokines/small extracellular vesicles (sEVs) released from muscle fibres regulate metabolism in muscle and extramuscular tissues in an autocrine/paracrine/endocrine manner during muscle atrophy. It is still unclear whether myokines/sEVs derived from muscle fibres can affect satellite cell function during ageing. METHODS: Aged mice were used to investigate changes in the myogenic capacity of SCs during ageing-induced muscle atrophy. The effects of atrophic myotube-derived sEVs on satellite cell differentiation were investigated by biochemical methods and immunofluorescence staining. Small RNA sequencing was performed to identify differentially expressed sEV microRNAs (miRNAs) between the control myotubes and atrophic myotubes. The target genes of the miRNA were predicted by bioinformatics analysis and verified by luciferase activity assays. The effects of identified miRNA on the myogenic capacity of SCs in vivo were investigated by intramuscular injection of adeno-associated virus (AAV) to overexpress or silence miRNA in skeletal muscle. RESULTS: Our study showed that the myogenic capacity of SCs was significantly decreased (50%, n = 6, P < 0.001) in the tibialis anterior muscle of aged mice. We showed that atrophic myotube-derived sEVs inhibited satellite cell differentiation in vitro (n = 3, P < 0.001) and in vivo (35%, n = 6, P < 0.05). We also found that miR-690 was the most highly enriched miRNA among all the screened sEV miRNAs in atrophic myotubes [Log2 (Fold Change) = 7, P < 0.001], which was verified in the atrophic muscle of aged mice (threefold, n = 6, P < 0.001) and aged men with mean age of 71 ± 5.27 years (2.8-fold, n = 10, P < 0.001). MiR-690 can inhibit myogenic capacity of SCs by targeting myocyte enhancer factor 2, including Mef2a, Mef2c and Mef2d, in vitro (n = 3, P < 0.05) and in vivo (n = 6, P < 0.05). Specific silencing of miR-690 in the muscle can promote satellite cell differentiation (n = 6, P < 0.001) and alleviate muscle atrophy in aged mice (n = 6, P < 0.001). CONCLUSIONS: Our study demonstrated that atrophic muscle fibre-derived sEV miR-690 may inhibit satellite cell differentiation by targeting myocyte enhancer factor 2 during ageing.

The changes of the calf-vein deformation and femoral vein peak velocity during ankle pump exercise with or without graduated compression stockings.

OBJECTIVES: To analyze the changes of lower limb hemodynamics parameters before and after wearing graduated compression stockings (GCS) during ankle pump exercise in patients preparing for arthroplastic surgery. METHOD: The leg veins of 16 patients awaiting arthroplasty were analyzed using a Sonosite M-Turbo ultrasound system during ankle pump exercise with or without GCS. The age of them was 70 ± 7 years (mean ± SD) (range 56-82 years) and body mass index was 25.8 ± 3.0 kg/m2 (range 18.0-30.5 kg/m2). Measured data including the cross-sectional area (CSA), anteroposterior (AP) diameter and lateromedial (LM) diameter of the soleus vein (SV), posterior tibial vein (PTV) and great saphenous vein (GSV). Additionally, the peak velocities of femoral vein (FV) were also measured. RESULTS: GCS could significantly decrease the cross-sectional area of SV, PTV and GSV in supine position at rest and maximum ankle plantar flexion. But the compression effect of GCS to SV and GSV was not observed during maximum ankle dorsiflexion. It was found that GCS application reduced the peak flow velocity of the femoral vein from 61.85 cm/s (95% CI = 50.94-72.75 cm/s) to 38.01 cm/s (95% CI = 28.42-47.59 cm/s) (P < 0.001) during ankle plantar flexion and decreased the femoral vein in these patients from 80.65 cm/s (95% CI = 70.37-90.92 cm/s) to 51.15 cm/s (95% CI = 42.58-59.73 cm/s) (P < 0.001) during ankle dorsiflexion. But this effect was not significant in supine position at rest. CONCLUSIONS: GCS could significantly reduce the peak flow velocity of the femoral vein during ankle pump exercise in the patients preparing for arthroplastic surgery.

Recent Advances in Bioengineered Scaffolds for Cutaneous Wound Healing.

Wound healing is an evolved dynamic biological process. Though many research and clinical approaches have been explored to restore damaged or diseased skin, the current treatment for deep cutaneous injuries is far from being perfect, and the ideal regenerative therapy remains a significant challenge. Of all treatments, bioengineered scaffolds play a key role and represent great progress in wound repair and skin regeneration. In this review, we focus on the latest advancement in biomaterial scaffolds for wound healing. We discuss the emerging philosophy of designing biomaterial scaffolds, followed by precursor development. We pay particular attention to the therapeutic interventions of bioengineered scaffolds for cutaneous wound healing, and their dual effects while conjugating with bioactive molecules, stem cells, and even immunomodulation. As we review the advancement and the challenges of the current strategies, we also discuss the prospects of scaffold development for wound healing.

Insight into the mechanism and formation process of bioinspired poly(amino acid)/polyphenol capsules engineered with fast pH switchable permeability.

Capsules have hollow cores and closed wall structures, and they have attracted considerable interest due to their wide applications and significance in life science. The engineering process of bioinspired capsules and related applications have earned heavy concerns. However, the mechanism of capsule formation is often ignored. Herein, based on polyornithine (POR) and tannic acid (TA), two facile strategies to engineer bioinspired capsules were proposed, and the formation mechanisms were deeply explored. We found that the oxidized state of TA had a profound influence not on the thickness or permeability of the formed capsule but on the mechanism and generation process. Compared to TA/POR capsules produced from TA without oxidization (TA/POR), capsules produced from TA with preoxidization (oTA/POR) had thicker shells with higher impermeability. The dominant construction mode in the shells of TA/POR capsules was electrostatic interactions but became Schiff base bonds in oTA/POR capsules. The permeability of oTA/POR displayed pH reversibility and strong pH dependence, with 100% permeability at lower pH and 100% impermeability at pH 7, completing loading/releasing kinetics in minutes at pH 4. We believe these findings contribute to knowledge of bioinspired capsules from engineering processes and formation mechanisms, extending their applications in various fields, such as in drug delivery, artificial cells, and sensors.

METTL3-mediated m6A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression.

OBJECTIVE: The aim of the study was to investigate the role and regulatory mechanisms of fibroblast-like synoviocytes (FLSs) and their senescence in the progression of osteoarthritis (OA). METHODS: Synovial tissues from normal patients and patients with OA were collected. Synovium FLS senescence was analysed by immunofluorescence and western blotting. The role of methyltransferase-like 3 (METTL3) in autophagy regulation was explored using N6-methyladenosine (m6A)-methylated RNA and RNA immunoprecipitation assays. Mice subjected to destabilisation of the medial meniscus (DMM) surgery were intra-articularly injected with or without pAAV9 loaded with small interfering RNA (siRNA) targeting METTL3. Histological analysis was performed to determine cartilage damage. RESULTS: Senescent FLSs were markedly increased with the progression of OA in patients and mouse models. We determined that impaired autophagy occurred in OA-FLS, resulting in the upregulation of senescence-associated secretory phenotype (SASP). Re-establishment of autophagy reversed the senescent phenotype by suppressing GATA4. Further, we observed for the first time that excessive m6A modification negatively regulated autophagy in OA-FLS. Mechanistically, METTL3-mediated m6A modification decreased the expression of autophagy-related 7, an E-1 enzyme crucial for the formation of autophagosomes, by attenuating its RNA stability. Silencing METTL3 enhanced autophagic flux and inhibited SASP expression in OA-FLS. Intra-articular injection of synovium-targeted METTL3 siRNA suppressed cellular senescence propagation in joints and ameliorated DMM-induced cartilage destruction. CONCLUSIONS: Our study revealed the important role of FLS senescence in OA progression. Targeted METTL3 inhibition could alleviate the senescence of FLS and limit OA development in experimental animal models, providing a potential strategy for OA therapy.

Effect of the stiffness of one-layer protein-based microcapsules on dendritic cell uptake and endocytic mechanism.

Microcapsules are one of the most promising microscale drug carriers due to their facile fabrication, excellent deformability, and high efficacy in drug storage and delivery. Understanding the effects of their physicochemical properties (size, shape, rigidity, charge, surface chemistry, etc.) on both in vitro and in vivo performance is not only highly significant and interesting but also very challenging. Stiffness, an important design parameter, has been extensively explored in recent years, but how the rigidity of particles influences cellular internalization and uptake mechanisms remains controversial. Here, one-layered lysozyme-based microcapsules with well-controlled stiffness (modulus ranging from 3.49 ± 0.18 MPa to 26.14 ± 1.09 MPa) were prepared and used to investigate the effect of stiffness on the uptake process in dendritic cells and the underlying mechanism. The cellular uptake process and endocytic mechanism were investigated with laser scanning confocal microscopy, mechanism inhibitors, and pathway-specific antibody staining. Our data demonstrated that the stiffness of protein-based microcapsules could be a strong regulator of intracellular uptake and endocytic kinetics but had no obvious effect on the endocytic mechanism. We believe our results will provide a basic understanding of the intracellular uptake process of microcapsules and the endocytic mechanism and inspire strategies for the further design of potential drug delivery microcarriers.

Network Pharmacology-Based Strategy for the Investigation of the Anti-Osteoporosis Effects and Underlying Mechanism of Zhuangguguanjie Formulation.

As the society is aging, the increasing prevalence of osteoporosis has generated huge social and economic impact, while the drug therapy for osteoporosis is limited due to multiple targets involved in this disease. Zhuangguguanjie formulation (ZG) is extensively used in the clinical treatment of bone and joint diseases, but the underlying mechanism has not been fully described. This study aimed to examine the therapeutic effect and potential mechanism of ZG on postmenopausal osteoporosis. The ovariectomized (OVX) mice were treated with normal saline or ZG for 4 weeks after ovariectomy following a series of analyses. The bone mass density (BMD) and trabecular parameters were examined by micro-CT. Bone remodeling was evaluated by the bone histomorphometry analysis and ELISA assay of bone turnover biomarkers in serum. The possible drug-disease common targets were analyzed by network pharmacology. To predict the potential biological processes and related pathways, GO/KEGG enrichment analysis was performed. The effects of ZG on the differentiation phenotype of osteoclasts and osteoblasts and the predicted pathway were verified in vitro. The results showed that ZG significantly improved the bone mass and micro-trabecular architecture in OVX mice compared with untreated OVX mice. ZG could promote bone formation and inhibit bone resorption to ameliorate ovariectomy-induced osteoporosis as evidenced by increased number of osteoblast (N.Ob/Tb.Pm) and decreased number of osteoclast (N.Oc/Tb.Pm) in treated group compared with untreated OVX mice. After identifying potential drug-disease common targets by network pharmacology, GO enrichment analysis predicted that ZG might affect various biological processes including osteoblastic differentiation and osteoclast differentiation. The KEGG enrichment analysis suggested that PI3K/Akt and mTOR signaling pathways could be the possible pathways. Furthermore, the experiments in vitro validated our findings. ZG significantly down-regulated the expression of osteoclast differentiation markers, reduced osteoclastic resorption, and inhibited the phosphorylation of PI3K/Akt, while ZG obviously up-regulated the expression of osteogenic biomarkers, promoted the formation of calcium nodules, and hampered the phosphorylation of 70S6K1/mTOR, which can be reversed by the corresponding pathway activator. Thus, our study suggested that ZG could inhibit the PI3K/Akt signaling pathway to reduce osteoclastic bone resorption as well as hamper the mTORC1/S6K1 signaling pathway to promote osteoblastic bone formation.

Preparing printable bacterial cellulose based gelatin gel to promote in vivo bone regeneration.

The naturally tight entanglement of fibers in bacterial cellulose (BC) results in low printability when BC is used as a bioink for printing scaffolds. In this study, neat BC was treated by TEMPO-mediated oxidation (TO-BC) and maleic acid (MA-BC) to prepare homogeneous BC dispersions to fabricate scaffolds for bone regeneration. Results showed that the treatments released individual fibrils in the corresponding uniform dispersions without impairing inherent crystalline properties. Compared with TO-BC, MA-BC hybridized with gelatin could endow the gel with improved rheological properties and compression modulus for 3D printing. Both TO-BC and MA-BC dispersions showed good osteoblast viability. However, MA-BC possessed more pronounced ability to express osteogenic marker genes and formation of mineralized nodules in vitro. Compared with TO-BC-based gelatin scaffolds, MA-BC-based gelatin scaffolds showed a better ability to stimulate the regeneration of rat calvaria, demonstrating a higher bone mineral density of newly formed bone and trabecular thickness in vivo.

Prognostic factors related to ambulation deterioration after 1-year of geriatric hip fracture in a Chinese population.

The objective of this study was to investigate the prognostic factors predicting the ambulation recovery of fragility hip fracture patients. 2286 fragility hip fracture patients were collected from the Fragility Fracture Registry in Hong Kong. Predictive factors of ambulation deterioration including age, gender, pre-operation American Society of Anesthesiologists grade, pre-fracture mobility, delay to surgery, length of stay, fracture type, type of surgery, discharge destination and complications were identified. Patients with outdoor unassisted and outdoor with aids ambulatory function before fracture had 3- and 1.5-times increased risk of mobility deterioration, respectively (Odds Ratio (OR) = 2.556 and 1.480, 95% Confidence Interval (CI) 2.101-3.111 and 1.246-1.757, both p < 0.001). Patients living in old age homes had almost 1.4 times increased risk of deterioration when compared to those that lived in their homes (OR = 1.363, 95% CI 1.147-1.619, p < 0.001). The risk also increased for every 10 years of age (OR = 1.831, 95% CI 1.607-2.086, p < 0.001). Patients in the higher risk ASA group shows a decreased risk of ambulation deterioration compared to those in lower risk ASA group (OR = 0.831, 95% CI 0.698-0.988, p = 0.038). Patients who suffered from complications after surgery did not increased risk of mobility decline at 1-year post-surgery. Delayed surgery over 48 h, delayed discharge (> 14 days), early discharge (less than 6 days), and length of stay also did not increased risk of mobility decline. Male patients performed worse in terms of their mobility function after surgery compared to female patients (OR = 1.195, 95% CI 1.070-1.335, p = 0.002). This study identified that better premorbid good function, discharge to old age homes especially newly institutionalized patients, increased age, lower ASA score, and male patients, correlate with mobility deterioration at 1-year post-surgery. With the aging population and development of FLS, prompt identification of at-risk patients should be performed for prevention of deterioration.

Sheltering proteins from protease-mediated degradation and a de novo strategy for preventing acute liver injury.

Restoring protein functions or supplying proteins is considered one of the most powerful therapeutic strategies for many diseases, but it is mainly limited by the denaturation of proteins during encapsulation and degradation by proteases during in vivo delivery, and limits its delivery. Herein, by encapsulating a protein (catalase, an enzyme) in a hexahistidine-metal assembly (HmA) via a de novo strategy under mild conditions, we demonstrated that HmA could maintain the bioactivity of the enzyme, protect the enzyme from proteinase degradation, and deliver the encapsulated protein for the prevention of disease in an acute liver injury model.

Citrate-Stabilized Gold Nanorods-Directed Osteogenic Differentiation of Multiple Cells.

OBJECTIVE: Gold nanorods (AuNRs) show great potential for versatile biomedical applications, such as stem cell therapy and bone tissue engineering. However, as an indispensable shape-directing agent for the growth of AuNRs, cetyltrimethylammonium bromide (CTAB) is not optimal for biological studies because it forms a cytotoxic bilayer on the AuNR surface, which interferes with the interactions with biological cells. METHODS: Citrate-stabilized AuNRs with various aspect-ratios (Cit-NRI, Cit-NRII, and Cit-NRIII) were prepared by the combination of end-selective etching and poly(sodium 4-styrenesulfonate)-assisted ligand exchange method. Their effects on osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1), rat bone marrow mesenchymal stem cells (rBMSCs), and human periodontal ligament progenitor cells (PDLPs) have been investigated. Potential signaling pathway of citrate-stabilized AuNRs-induced osteogenic effects was also investigated. RESULTS: The experimental results showed that citrate-stabilized AuNRs have superior biocompatibility and undergo aspect-ratio-dependent osteogenic differentiation via expression of osteogenic marker genes, alkaline phosphatase (ALP) activity and formation of mineralized nodule. Furthermore, Wnt/ß-catenin signaling pathway might provide a potential explanation for the citrate-stabilized AuNRs-mediated osteogenic differentiation. CONCLUSION: These findings revealed that citrate-stabilized AuNRs with great biocompatibility could regulate the osteogenic differentiation of multiple cell types through Wnt/ß-catenin signaling pathway, which promote innovative AuNRs in the field of tissue engineering and other biomedical applications.

Prevalence and Risk Factors of Preoperative Deep Vein Thrombosis in Patients with End-Stage Knee Osteoarthritis.

BACKGROUND: The purpose of this study is to determine the prevalence and the risk factors of DVT in end-stage OA patients. METHODS: From March 2015 to June 2017, 521 patients with knee degenerative osteoarthritis undergoing knee arthroplasty were enrolled; 458 patients (87.9%) were admitted for primary total knee arthroplasty and 63 patients (12.1%) were admitted for unicompartmental knee arthroplasty. Parameters were compared using χ2 or t-test for both the groups. Binary logistic regression analysis was used to determine risk factors. RESULTS: The incidence of preoperative DVT was 6.7% (n = 35). Age in preoperative DVT group was significantly more than the non-DVT group (72.54 ± 6.53 vs. 68.65 ± 7.35, P = 0.002). Preoperative D-dimer >0.5 µg/mL (P < 0.001) was also associated with preoperative DVT in knee osteoarthritis patients. The incidence increased with age significantly (2.17% in <65 years, 6.86% in ≥65 <75 years, and 12.26% in ≥75 years) (P = 0.008). Thus, age (P = 0.041, OR 1.075, 95% CI [1.002-1.110]) and D-dimer >0.5 µg/mL (P < 0.001, OR 4.441, 95% CI [1.942-10.153]) were the independent risk factors for preoperative DVT in knee osteoarthritis patients. CONCLUSIONS: The incidence of DVT in end-stage osteoarthritis was 6.7%. The results suggest that older people aged over 75 and D-dimer > 0.5 µg/mL were risk factors for DVT among patients admitted to the hospital for total knee arthroplasty. Instrumental screening should be encouraged, especially in subgroups at higher risk for preoperative DVT.