The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study.

BACKGROUND: There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety. METHODS: A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery. RESULTS: There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE. CONCLUSION: This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.

Changes in clinical outcomes and alignment of the ipsilateral knee and ankle after supramalleolar osteotomy in patients with varus osteoarthritis of the ankle: a short-term follow-up study.

PURPOSE: The purpose of this study was to investigate the changes in clinical outcomes and alignment of the ipsilateral knee and ankle in patients with varus ankle osteoarthritis after supramalleolar osteotomy (SMO). METHODS: We retrospectively reviewed 23 patients (24 ankles) with Takakura II, IIIa and IIIb ankle osteoarthritis treated with SMO between May 2017 and March 2022. The radiologic parameters of ankles contained medial distal tibial angle (TAS), tibiotalar angle (TT), tibial lateral surface (TLS), tibial plafond inclination (TPI) and talar inclination (TI). The radiologic parameters of knees contained medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), the knee joint line orientation relative to ground (G-KJLO) and WBL. Hip-knee-ankle angle (HKA) was also collected. The Takakura system was used for evaluating the ankle osteoarthritis and the Kellgren-Lawrence (KL) system was used for evaluating the knee osteoarthritis. Clinical evaluation of the ankle joints contained American Orthopedic Foot and Ankle Society (AOFAS), range of motion (ROM) and visual analogue scale (VAS). Clinical evaluation of the knee joints contained Japanese Orthopaedic Association Scores (JOA), ROM, VAS. RESULTS: The mean follow-up times were 20.3 ± 7.3 months (range 12-38). According to the radiologic evaluation, the TAS increased from preoperative 84.7° ± 2.0° to 91.2° ± 1.8° at the last follow-up (P < 0.001). The TPI and TI decreased from 4.4° ± 4.2° and 11.0° ± 5.2° to 0.1° ± 4.7° and 4.1° ± 4.8° (P < 0.001 for both). The TT angel improved from 9.5° ± 4.1° to 4.9° ± 3.3° (P < 0.001). No significant differences were found regarding MPTA, JLCA, G-KJLO, knee WBL and HKA (P > 0.05 for all). The Takakura stage improved after SMO (P < 0.001) whilst the KL stage maintains the similar lever (P > 0.05). According to the clinical evaluation, the AOFAS significantly increased from 67.5 ± 10.6 to 88.5 ± 9.3 and the VAS of the ankle decreased from 4.7 ± 1.6 to 1.2 ± 1.1, whilst there were no changes on VAS and even the JOA and knee ROM after SMO (P > 0.05 for all). CONCLUSIONS: SMO can alleviate the symptoms of varus ankle osteoarthritis and delay the time for ankle replacement or arthrodesis by redistributing the abnormal stress of the ankle and restoring the congruence of the tibiotalar joint. In addition, it did not induce the clinical symptoms of knee without compromising lower limb alignment or knee joint line orientation in the short term. LEVEL OF EVIDENCE: Level IV case series.

Advancing treatment strategies for posterior malleolar malunion: The ankle dislocation method.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.

Talonavicular-cuneiform arthrodesis for the treatment of Müller-Weiss: mid-term results of 15 cases after 5 years.

BACKGROUND: There is no gold standard for the operative treatment of patients with Müller-Weiss disease (MWD). This study reports the mid-term follow-up results for at least 5 years following talonavicular-cuneiform (TNC) arthrodesis for Müller-Weiss disease. METHODS: A total of 15 patients undergoing TNC arthrodesis for MWD were retrospectively reviewed between January 2015 and August 2017. Two senior doctors assessed the radiographic results twice at each visit (preoperative, three months after the operation, and final follow-up). The clinical results and complications from preoperative and final follow-up were recorded. RESULTS: The mean follow up period was 74.0 (range 64 to 90) months. The calcaneal pitch angle, lateral Meary's angle, anteroposterior (AP) Meary's angle, AP talocalcaneal angle, and talonavicular coverage were significantly different before and three months after the operation (p < 0.05). There was no significant difference between the radiographic results of three months after the operation and the final follow-up (p > 0.05). The radiological measurements of the two senior doctors were calculated and found to be moderate to strong (ICC:0.899-0.995). The AOFAS, VAS, and SF-12 scores significantly improved at the last follow-up compared to those before the operation (p < 0.05). Two patients experienced early complications, four had late complications, and one underwent a second operation of midfoot fusion with calcaneal osteotomy. CONCLUSION: This research confirms that using TNC arthrodesis for the treatment of MWD can substantially improve the clinical and radiographic results. These results were maintained until mid-term follow-up.

Medial malleolar window approach for varus-type tibial pilon fractures: a retrospective study.

PURPOSE: Choosing a suitable surgical approach is crucial and challenging for type C pilon fractures. This article aims to explore the clinical efficacy of the medial malleolar window approach for varus-type tibial pilon fractures. METHODS: A retrospective analysis was conducted on 38 patients with type C varus-type pilon fractures treated between May 2018 and June 2021. In total, 16 cases underwent surgical treatment through the medial malleolar window approach and 22 cases were treated with the traditional anteromedial approach combined with a posterior approach. The operation time, hospitalization time, fracture healing time, the American Orthopedic Foot and Ankle score, Visual Analogue Scale, and complications were recorded to comprehensively evaluate the clinical efficacy of the technique. Fracture reduction quality was evaluated using the criteria proposed by Burwell and Charnley. RESULTS: All patients were followed up. No patients presented delayed union or nonunion. Compared with the conventional approach, the medial malleolar window approach had the advantage of better clinical effect recovery and better fracture reduction (P < 0.05). Meanwhile, the medial malleolar window approach had a shorter operation time, although the statistics suggest no significant difference with the control group. No implant exposure or infection occurred. There was good wound healing at two weeks after surgery in all but two cases. Local wound edge necrosis developed in one case in the medial malleolar window approach group, and the wound could not be closed at one stage in another case in the conventional group because of excessive tension, requiring secondary closure. CONCLUSION: The medial malleolar window approach provides excellent exposure to type C pilon fractures, allowing for satisfactory fracture reduction and functional rehabilitation. The medial window approach is recommended for varus-type pilon fractures, which can effectively avoid a posterior incision and reduce the operation time.

A novel distractor-assisted reduction combined with the sinus tarsi approach for joint depression-type calcaneal fractures.

PURPOSE: A novel percutaneous distractor with the advantage of axial and direct distraction was designed for the minimally invasive treatment of calcaneal fractures. The purpose of this study was to investigate the clinical results and complications of a novel distractor combined with sinus tarsi approach (STA) in treatment of the joint depression-type of calcaneal fractures. METHODS: Fifty-four patients with the depression-type of calcaneal fractures (30 Sanders type II, 22 Sanders type III, 2 Sanders type IV) who were subjected to the novel distractor combined with STA were retrospectively assessed. Calcaneal height, width, and length; Bohler's angle; and the Gissane angle were evaluated pre-operatively and post-operatively. Clinical outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) and visual analog scale (VAS) pain scores from the last follow-up. Complications were also recorded. RESULTS: Fifty-two patients achieved an average follow-up of 24.3 months (range 18 to 34 months), and two patients were lost to follow-up six months post-operatively. There was significant difference between pre-operative and post-operative calcaneal height, width, and length; Bohler's angle; and Gissane angle (p < 0.01), but no significant difference was detected between the post-operative and normal side Bohler's angle (p > 0.05). The AOFAS ankle and hind foot score was 88.4 ± 6.6, and the VAS score was 1.9 ± 0.7 at the last follow-up. Nine (17.3%) patients developed complications: One experienced skin necrosis and two had screws loosening; three patients developed early degenerative changes of the subtalar joint; two had no symptoms; one had light pain around the subtalar joint without medical treatment; complex regional pain syndrome (CRPS) developed in one patient after seven months post-operatively; and two developed transient ankle stiffness. CONCLUSION: The novel distractor combined with the STA effectively reconstructs the facet depression-type of calcaneal fractures (sanders type II and III) with minimal complications.

Absorbable suture anchor and knotless anchor techniques produced similar outcomes in arthroscopic anterior talofibular ligament repair.

PURPOSE: The purpose of this study is to compare absorbable suture anchor with knotless anchor techniques for arthroscopic anterior talofibular ligament (ATFL) repair. METHOD: A multicenter retrospective study was performed with 185 patients, who had undergone an arthroscopic ATFL repair procedure using absorbable suture anchor or knotless anchor between May 2017 and October 2019. The follow-up time was a minimum of 18 months. Karlsson-Peterson score, visual analogue scale (VAS), and Cumberland ankle instability tool (CAIT) were evaluated. The complications were also recorded. RESULTS: One hundred and seven patients underwent one absorbable suture anchor repair procedure (Group A [A]), and the other seventy-eight patients underwent one knotless anchor repair procedure (Group B [B]). At the final follow-up, both Karlsson-Peterson score (A, pre 61.0 ± 8.0 vs post 93.5 ± 5.3, P < 0.001; B, pre 59.5 ± 8.2 vs post 92.4 ± 6.3, P < 0.001), VAS score (A, pre 5.0 ± 1.3 vs post 0.5 ± 0.7, P < 0.001; B, pre 5.5 ± 1.2 vs post 0.9 ± 1.0, P < 0.001), and CAIT score (A, pre 53.1 ± 12.0 vs post 93.1 ± 6.6, P < 0.001; B, pre 51.6 ± 12.0 vs post 93.1 ± 6.5, P < 0.001) improved significantly in both groups. There was no significant difference between the two groups regarding the Karlsson-Peterson score (A, pre 61.0 ± 8.0 vs B, pre 59.5 ± 8.2, n.s; A, post 93.5 ± 5.3 vs B, post 92.4 ± 6.3, n.s), CAIT score (A, pre 53.1 ± 12.0 vs B, pre 51.6 ± 12.0, n.s; A, post 93.1 ± 6.6 vs B, post 93.1 ± 6.5, n.s) and the change ranges of VAS (A, 4.5 ± 1.0 vs B, 4.6 ± 1.2, n.s). Anchor complications were easier to occur in Group B (0/107 vs 6/78, P = 0.007). Knot irritation slightly increased in Group A (10/107 vs 0/78, P = 0.006). No significant difference was found regarding total complication rates (A, 10/107 vs B, 6/78, n.s). CONCLUSION: Absorbable suture anchor and knotless anchor for arthroscopic ATFL repair produced similar clinical outcomes. The ankle stability scores increased significantly in both groups. However, the knotless anchor has a higher risk to loosen, deviated direction or break, while the absorbable suture anchor still has a slim chance of knot irritation. LEVEL OF EVIDENCE: III.

[Comparison of talonavicular-cuneiform joint fusion with bone grafting and without bone grafting in treatment of Müller-Weiss disease].

Objective: To compare the effectiveness of talonavicular-cuneiform joint fusion with iliac bone grafting and without bone grafting in the treatment of Müller-Weiss diseases (MWD). Methods: The clinical data of 44 patients (44 feet) with MWD who received talonavicular-cuneiform joint fusion between January 2017 and November 2022 and met the selection criteria was retrospectively analyzed. Among them, 25 patients were treated with structural iliac bone grafting (bone grafting group) and 19 patients without bone grafting (non-bone grafting group). There was no significant difference ( P>0.05) in age, gender composition, body mass index, disease duration, affected side, Maceira stage, and preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) score, anteroposterior/lateral Meary angle, and Pitch angle between the two groups. Operation time, operation cost, and postoperative complications were recorded in the two groups. AOFAS and VAS scores were used to evaluate the function and pain degree of the affected foot. Meary angle and Pitch angle were measured on the X-ray film, and the joint fusion was observed after operation. The difference (change value) of the above indexes before and after operation was calculated for comparison between groups to evaluate the difference in effectiveness. Results: The operation was successfully completed in both groups, and the incisions in the two groups healed by first intention. The operation time and cost in the bone grafting group were significantly more than those in the non-bone grafting group ( P<0.05). All patients were followed up. The median follow-up time was 41.0 months (range, 16-77 months) in the non-bone grafting group and 40.0 months (range, 16-80 months) in the bone grafting group. There was skin numbness of the medial dorsalis of the foot in 1 case, internal fixation stimulation in 2 cases, and pain at the iliac bone harvesting area in 1 case of the bone grafting group. There was skin numbness of the medial dorsalis of the foot in 1 case and muscle atrophy of the lower limb in 1 case of the non-bone grafting group. There was no significant difference in the incidence of complications between the two groups ( P>0.05). At last follow-up, the AOFAS scores of the two groups significantly improved when compared with those before operation, while the VAS scores significantly decreased, the anteroposterior/lateral Meary angle and Pitch angle significantly improved, and the differences were significant ( P<0.05). There was no significant difference in the change values of outcome indicators between the two groups ( P>0.05). There was no delayed bone union or bone nonunion in both groups, and joint fusion was achieved at last follow-up. Conclusion: In the treatment of MWD, there is no significant difference in effectiveness and imaging improvement of talonavicular-cuneiform joint fusion combined with or without bone grafting. However, non-bone grafting can shorten the operation time, reduce the cost, and may avoid the complications of bone donor site.

Glucose microenvironment sensitive degradation of arginine modified calcium sulfate reinforced poly(lactide-co-glycolide) composite scaffolds.

Poly(lactide-co-glycolide) (PLGA) and calcium sulfate composites are promising biodegradable biomaterials but are still challenging to use in people with high levels of blood glucose or diabetes. To date, the influence of glucose on their degradation has not yet been elucidated and thus calls for more research attention. Herein, a novel calcium sulfate whisker with L-arginine was used to effectively tune its crystal morphology and was employed as a reinforced phase to construct the PLGA-based composite scaffolds (ArgCSH/PLGA) with a sleeve porous structure. ArgCSH/PLGA showed excellent elastic modulus and strength in the compression and bending models. Moreover, an in vitro immersion test showed that ArgCSH/PLGA possessed degradation and redeposition behaviors sensitive to glucose concentration, and the adsorbed Arg played a crucial role in the degradation process. The subsequent cell functional evaluation showed that ArgCSH could effectively protect cells from damage caused by AGEs and promote osteogenic differentiation. The corresponding degradation products of ArgCSH/PLGA displayed the ability to regulate osteoblast bone differentiation and accelerate matrix mineralization. These findings provide new insights into the interaction between biomaterials and the physiological environment, which may be useful in expanding the targeted choice of efficient bone graft biodegradable materials for diabetic osteoporosis.

Müller-Weiss Disease: Midfoot Arthrodesis in Reduction vs Malreduction.

BACKGROUND: Midfoot arthrodesis is regarded as the main surgical approach for treating Müller-Weiss disease (MWD). This study aimed to investigate the incidence of postoperative pain during MWD treatment through midfoot reduction or malreduction during arthrodesis and to explore the factors influencing postoperative pain in patients with MWD. METHODS: A total of 67 patients with MWD were recruited and divided into two groups according to whether midfoot alignment was reduced: reduction group (n = 38) and malreduction group (n = 29). Demographic characteristics before the operation and at the last follow-up, as well as clinical and radiographic parameters, were compared between the two groups. Clinical parameters included the American Orthopaedic Foot & Ankle Society score and visual analog scale score, whereas radiographic parameters included the calcaneal pitch angle, lateral Meary's angle, talometatarsal-1 angle dorsoplantar (TMT1dp), talocalcaneal angle dorsoplantar (Kite angle), talonavicular coverage angle, and medial navicular pole extrusion. Postoperative complications and incidence of midfoot pain were evaluated at the last follow-up visit. RESULTS: The reduction group exhibited better clinical and radiological parameters, including the TMT1dp and medial navicular pole extrusion, than the malreduction group at the last follow-up (all P < .05). However, the calcaneal pitch angle, lateral Meary's angle, Kite angle, and talonavicular coverage angle did not significantly differ between the two groups (all P > .05). The overall incidence of midfoot pain was 26.4%. The reduction group showed a lower incidence of medial pain than the malreduction group (15.7% vs. 40.0%, P < .05). Regression analysis revealed that midfoot abduction, represented by the TMT1dp, was a critical factor for midfoot arthrodesis failure and that medial navicular pole extrusion was not correlated with postoperative midfoot pain. CONCLUSION: Midfoot reduction arthrodesis yields better clinical outcomes than malreduction arthrodesis. The TMT1dp, representing midfoot abduction, is a key factor for midfoot arthrodesis failure. The extruded medial navicular bone may not affect postoperative medial midfoot pain. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

[Influence and risk factors of lateral hinge fracture on early effectiveness of supramalleolar osteotomy].

Objective: To evaluate the influence of lateral hinge fracture (LHF) on the early effectiveness of supramalleolar osteotomy (SMO) and to explore the related risk factors for LHF. Methods: A total of 39 patients (39 feet) with varus-type ankle osteoarthritis treated with SMO between January 2016 and December 2022 were analyzed retrospectively. There were 10 males and 29 females, aged from 41 to 71 years (mean, 57.7 years). According to Takakura stage, there were 6 feet in stage Ⅱ, 19 feet in stage Ⅲa, and 14 feet in stage Ⅲb. The LHF was recognized by the immediate postoperative X-ray film. The osteotomy healing time and the changes of pain visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, tibial anterior surface angle (TAS), tibial lateral surface angle (TLS), and tibiotalar angle (TT) before and after operation were compared between patients with and without LHF. The age, gender, affected side, body mass index, Takakura stage, preoperative VAS score, preoperative AOFAS score, preoperative TAS, preoperative TLS, preoperative TT, SMO correction angle, osteotomy distraction, distance from medial osteotomy to ankle joint line (MD), and distance from lateral osteotomy to ankle joint line (LD) were compared between with and without LHF patients, and further logistic regression analysis was used to screen the risk factors of LHF during SMO. Results: All patients were followed up 12-54 months (mean, 27.1 months). During operation, 13 feet developed LHF (group A) and 26 feet did not develop LHF (group B). X-ray film reexamination showed that 1 patient in group A complicated with tibial articular surface cleft fracture had delayed osteotomy and healed successfully after plaster fixation; the osteotomy of other patients healed, and there was no significant difference in healing time between the two groups ( P>0.05). At last follow-up, there were significant differences in VAS score, AOFAS score, TAS, TLS, and TT of the two groups when compared with preoperative ones ( P<0.05), but there was no significant difference in the changes of above indicators before and after operation between the two groups ( P>0.05). The differences in SMO correction angle, osteotomy distraction, and LD between with and without LHF patients were significant ( P<0.05), and further logistic regression analysis showed that excessive LD was the risk factor of LHF during SMO ( P<0.05). Conclusion: Too high or too low lateral hinge position during SMO may lead to LHF, but as long as appropriate treatment and rehabilitation measurements are taken, the early effectiveness is similar to that of patients without LHF.

Magnetic nanocomposites for magneto-promoted osteogenesis: from simulation auxiliary design to experimental validation.

Magnetically actuated mechanical stimulation, as a novel form of intelligent responsive force stimulation, has a great potential for remote spatiotemporal regulation of a variety of life processes. Hence, the optimal design of magnetic nanomaterials for generating magneto-mechanical stimuli becomes an important driving force in the development of magneto-controlled biotherapy. This study aims to clarify the general rule that the surface modification amount of magnetic nanoparticles (NPs) affects the biological behavior (e.g., cell adhesion, proliferation and differentiation) of pre-osteoblast cells. First of all, course-grained molecular dynamics simulations predict that 23.3% graft modification of the NPs can maximize the heterogeneity of the dynamics of the polymer matrix, which may generate enhanced mechanical stimuli. Then, experimentally, iron oxide (IO) NPs grafted with different amounts of poly(γ-benzyl-L-glutamate) (PBLG) were prepared to obtain homogeneous magnetic nanocomposites with improved mechanical properties. Further in vitro cell experiments demonstrate that the grafting amounts of 21.46% and 32.34% of PBLG on IO NPs are the most beneficial for the adhesion and osteogenic differentiation of cells. Simultaneously, the maximized upregulation of the Piezo1 gene indicates that the cells receive the strongest magneto-mechanical stimuli. The consistent conclusion of the experiments and simulations indicates that 20-30% PBLG grafted on the IO surface could maximize the ability of magnetic stimuli to regulate the biological behavior of the cells, which validates the feasibility of simulation auxiliary material design and is of great importance for promoting the application of magneto-controlled biotherapy in bioengineering and biomedicine.

Multi-omics approach identifies PI3 as a biomarker for disease severity and hyper-keratinization in psoriasis.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disease. Psoriasis severity evaluation is important for clinicians in the assessment of disease severity and subsequent clinical decision making. However, no objective biomarker is available for accurately evaluating disease severity in psoriasis. OBJECTIVE: To define and compare biomarkers of disease severity and progression in psoriatic skin. METHODS: We performed proteome profiling to study the proteins circulating in the serum from patients with psoriasis, psoriatic arthritis and ankylosing spondylitis, and transcriptome sequencing to investigate the gene expression in skin from the same cohort. We then used machine learning approaches to evaluate different biomarker candidates across several independent cohorts. In order to reveal the cell-type specificity of different biomarkers, we also analyzed a single-cell dataset of skin samples. In-situ staining was applied for the validation of biomarker expression. RESULTS: We identified that the peptidase inhibitor 3 (PI3) was significantly correlated with the corresponding local skin gene expression, and was associated with disease severity. We applied machine learning methods to confirm that PI3 was an effective psoriasis classifier, Finally, we validated PI3 as psoriasis biomarker using in-situ staining and public datasets. Single-cell data and in-situ staining indicated that PI3 was specifically highly expressed in keratinocytes from psoriatic lesions. CONCLUSION: Our results suggest that PI3 may be a psoriasis-specific biomarker for disease severity and hyper-keratinization.

Construction of a virtual reality platform for computer-aided navigation Lingnan bone setting technique.

To establish a standard Traditional Chinese medicine (TCM) bone setting technique, standardize the operation and inherit the TCM bone setting technique. This project was based on the interactive tracking of bone setting techniques with a dedicated position tracker, the motion tracking of bone setting techniques based on RGBD (Red Green Blue Depth) cameras, the digital analysis of bone setting techniques, and the design of the virtual reality platform for bone setting techniques. These key technical researches were combined to construct an interactive bone setting technique. The virtual simulation system can reproduce the implementation process of the expert's bone setting technique. The user can observe the implementation of the manipulative technique from multiple angles; through human-computer interaction, the whole process of implementation of the bone setting technique can be simulated, and the movement and reduction of the affected bone can be observed at the same time. It can be used as a teaching and training system for assisting bone setting techniques. Students can use the system to carry out repeated self-training, and can instantly compare with the standard techniques of the expert database, breaking the traditional teaching mode of 'expected and unspeakable' and avoid directly using patients. Therefore, this research makes it possible to reduce teaching costs, reduce risks, improve teaching quality, and make up for the lack of teaching conditions. It is very positive for the inheritance of the traditional Chinese 'intangible culture' of bone setting techniques, and to promote the digitalization and standardization of bone setting techniques.

Using computer technology to digitally record bone-setting manipulations.Construct a virtual simulation system for interactive bone-setting manipulation.Promote the digitization and standardization of bone-setting techniques.

Y-shape osteotomy combined with subtalar arthrodesis for calcaneus malunion: a retrospective study.

BACKGROUND: This retrospective study aimed to introduce a novel method for simultaneous Y-shape osteotomy combined with subtalar arthrodesis for calcaneus malunion and to evaluate the feasibility of this method. METHODS: We retrospectively analysed the clinical and imaging data of 11 patients with calcaneus malunion treated using Y-shape osteotomy and subtalar arthrodesis who were admitted to our hospital from June 2018 to October 2020. The patients included 9 males and 2 females aged from 24 to 69 years old, with an average age of 42.18 years. The clinical and radiological results were assessed with the Visual Analogue Scale (VAS) pain score and American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. In addition, functional recovery and general quality of life were evaluated using the 12-Item Short-Form Survey (SF-12). RESULTS: All radiological parameters were significantly improved at the last follow-up, with increases of 14.37°, 9.18°, and 4.51 mm in the Böhler's angle, calcaneal pitch angle, and talocalcaneal height, respectively, and decreases of 6.39 mm and 6.18° in the calcaneal width and Hindfoot alignment angle (p < 0.05). The mean AOFAS and VAS scores at the last follow-up improved compared with those preoperatively, from 34.18 ± 9.53 to 84.18 ± 11.59 and from 6.90 ± 1.22 to 1.90 ± 1.13, respectively (p < 0.05). The SF-12 physical and mental health scores were 49.65 ± 6.84 and 52.68 ± 7.88, respectively. Furthermore, the early postoperative complications included skin necrosis in one and sural neuralgia in one patient, and the late postoperative complication included ankle pain in one patient. No other complications, such as implant discomforts, malunion, nonunion and re-fracture, were presented. CONCLUSION: These results indicate that Y-shape osteotomy combined with subtalar arthrodesis is an effective new method for the treatment of calcaneal malunion. Advantages include improvement of the anatomic shape of the calcaneus and union rates for subtalar arthrodesis.

Pb and Cd exposure linked with Il-10 and Il-13 gene polymorphisms in asthma risk relevant immunomodulation in children.

Genetic variants and environmental factor of heavy metal exposure accelerate the risk of immune-mediated respiratory diseases, including asthma in children. This study aims to investigate the effects and interaction of Pb, Cd exposure from e-waste and interleukin (IL)-10, IL-13 gene polymorphisms on interleukin expressions in children. Pb, Cd levels, Il-10 (rs1800871, rs1800872, rs1800896) and Il-13 (rs20541, rs1800925) polymorphisms were determined in blood or urine of 155 children (75 from e-waste-exposed area, Guiyu and 80 from reference area, Haojiang). Blood Pb and urine Cd levels of e-waste-exposed children were both higher (mean: 5.89 vs. 3.35 µg/dL; 6.04 vs. 1.82 µg/g, both P < 0.05). Exposed children had a larger proportion of high blood Pb level (> 5.00 µg/dL) (66.67% vs. 4.11%, P < 0.001), but they had no statistically different proportion of high urine Cd level (> 1.00 µg/g creatinine). Median levels of IL-13 decreased (3.674 vs. 4.410 ng/L, P < 0.01), but of IL-10 did not vary in serum of exposed children. The analyses revealed no significant associations of Pb or Cd with Il-10 or Il-13 gene polymorphisms. The high blood Pb and urine Cd level were respectively associated with the low IL-13 ( < 3.696 ng/L) and low IL-10 ( < 0.361 ng/L) level, after adjustment for children's age, gender, and BMI (both P ≤ 0.05). Children homozygous carrying major allele for Il-13 (rs20541 and rs1800925) had additive interactions with high blood Pb level on low IL-13 expression (OR = 5.37, 95% CI: 1.96, 14.73 and OR = 8.45, 95% CI: 2.61, 27.32; both P ≤ 0.001). In contrast, no interaction was observed amongst Pb or Cd with Il-10 gene polymorphisms on its expression. Our findings suggest that Pb exposure interacting with Il-13 gene polymorphisms negatively regulates IL-13 expression, which may pose a risk to abnormal asthma-relevant immunomodulation in preschool children.

The Protective Effect of Ginsenoside Rg1 on Apoptosis in Human Ankle Joint Traumatic Arthritis Chondrocytes.

The ankle biomechanics is easily changed due to the acute injury of the tissue around the ankle joint and the damage of the ankle joint structure, such as ankle instability and joint surface imbalance. When the mechanical load of the ankle changes, it can cause ankle regeneration and remodeling processes such as cartilage loss, bone remodeling, and degenerative changes. The aim of this study was to investigate the effect and mechanism of ginsenoside Rg1 against interleukin-1ß (IL-1ß)-induced apoptosis in human articular chondrocytes (HACs). The apoptosis model of HAC cells was established by IL-1ß induction, and then the HAC cells were cultured with different concentrations of Rg1. The protective effect of Rg1 on HAC cell apoptosis was investigated by detecting the changes of apoptosis and activity of PI3K/Akt/mitochondrial signaling pathway. The results showed that a specific concentration of Rg1 could promote the proliferation of IL-1ß-induced HAC cells and inhibit apoptosis. At the same time, Rg1 treatment with specific concentration can reduce the content of reactive oxygen species (ROS) and malondialdehyde (MDA) in HACs and improve the related expression of mitochondrial membrane potential (MMP). Furthermore, qRT-PCR and western blot results showed that Rg1 could improve the low expression of Bcl-2 and inhibit the high expression of Bax, caspase-3, caspase-8, caspase-9, FasL, AIF, and Cyto c in IL-1ß-induced cells. In summary, Rg1 can inhibit IL-1ß-induced apoptosis of HAC cells by decreasing the activity of PI3K/Akt/mitochondrial signaling pathway, and Rg1 has a protective effect on apoptosis of HAC cells.

Tannin-bridged magnetic responsive multifunctional hydrogel for enhanced wound healing by mechanical stimulation-induced early vascularization.

Wound healing is a complex process. Wound-repair materials require multiple functionalities, such as anti-inflammatory, antibacterial, angiogenesis, pro-proliferation, and remodeling. To achieve rapid tissue regeneration, magnetic field-assisted therapy has become a promising means. In this study, a homogeneous magnetic responsive nanocomposite hydrogel with enhanced mechanical properties was obtained through a tannin (TA)-assisted bridge between magneto-deformable cobalt ferrite nanoparticles (CFO NPs) and polyvinyl alcohol (PVA) matrix. In the presence of an external static magnetic field (SMF), the TA bridge could efficiently transmit magnetically actuated deformation to the PVA, which originated from the CFO NPs, generating a larger topographic change on the surface. The change of topography provided a mechanical cue to increase cell adhesion and proliferation. Moreover, due to the synergistic effects of TA modification and CFO NPs, the obtained magnetic responsive hydrogel exhibited considerable antibacterial activity. Furthermore, the results of in vivo study confirmed the anti-inflammatory properties of the TA-CFO/PVA hydrogel. More importantly, the TA-CFO/PVA hydrogel accelerated wound healing under a SMF, which contributed to the early vascularization induced by mechanical stimuli generated from the TA-CFO/PVA nanocomposite hydrogel. As a proof-of-concept, we provided an optimizing strategy for magneto-controlled skin tissue regeneration, which may have important guiding significance for the clinical application of magnetic field-assisted therapy.

Modulating the surface potential of microspheres by phase transition in strontium doped barium titanate to restore the electric microenvironment for bone regeneration.

The endogenous electrical potential generated by native bone and periosteum plays a key role in maintaining bone mass and quality. Inspired by the electrical properties of bone, different negative surface potentials are built on microspheres to restore electric microenvironment for powerful bone regeneration, which was prepared by the combination of strontium-doped barium titanate (Sr-BTO) nanoparticles and poly (lactic-co-glycolic acid) (PLGA) with high electrostatic voltage field (HEV). The surface potential was modulated through regulating the phase composition of nanoparticles in microspheres by the doping amount of strontium ion (Sr2+). As a result, the 0.1Sr-BTO/PLGA group shows the lowest surface potential and its relative permittivity is closer to natural bone. As expected, the 0.1Sr-BTO/PLGA microspheres performed cytocompatibility, osteogenic activity in vitro and enhance bone regeneration in vivo. Furthermore, the potential mechanism of Sr-BTO/PLGA microspheres to promote osteogenic differentiation was further explored. The lower surface potential generated on Sr-BTO/PLGA microspheres regulates cell membrane potential and leads to an increase in the intracellular calcium ion (Ca2+) concentration, which could activate the Calcineurin (CaN)/Nuclear factor of activated T-cells (NFAT) signaling pathway to promote osteogenic differentiation. This study established an effective method to modulate the surface potential, which provides a prospective exploration for electrical stimulation therapy. The 0.1Sr-BTO/PLGA microsphere with lower surface potential and bone-matched dielectric constant is expected to have great potential in the field of bone regeneration.

Endoscopically Assisted, Minimally Invasive Reconstruction for Chronic Achilles Tendon Rupture With a Double-Bundle Flexor Hallucis Longus.

BACKGROUND: High morbidity has been reported regarding Achilles tendon (AT) injuries, and the upward trend has accelerated since the mid-1990s. A chronic Achilles tendon rupture usually results from a neglected or misdiagnosed acute rupture, and about one-fifth of acute AT ruptures are missed and lead to chronic AT rupture. Although many techniques have been described, there is no gold standard in the treatment of chronic AT ruptures. HYPOTHESIS: Endoscopically assisted, minimally invasive reconstruction for chronic AT rupture using a double-bundle flexor hallucis longus (FHL) tendon would result in improvement of the overall function, with a low rate of wound complications. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between May 2015 and November 2016, a total of 19 consecutive patients were enrolled and treated using endoscopically assisted, minimally invasive reconstruction for chronic AT rupture using a double-bundle FHL. The operative assessment comprised the Achilles Tendon Total Rupture Score, the American Orthopaedic Foot & Ankle Society score, the Victorian Institute of Sports Assessment-Achilles score, and a postoperative questionnaire. All postoperative complications were recorded. RESULTS: The mean follow-up time for all patients was 31 months (range, 20-42 months). According to the postoperative questionnaire, the result of surgery was excellent in 8 (42%) of 19 patients, good in 10 (53%), and fair in 1 (5%). All clinical outcome scores (mean ± SD) improved significantly after surgery: Achilles Tendon Total Rupture Score, 23.3 ± 10.3 vs 98.3 ± 9.2 (postoperatively vs preoperatively); American Orthopaedic Foot & Ankle Society, 52.1 ± 12.4 vs 97.5 ± 18.9; and Victorian Institute of Sports Assessment-Achilles, 23.4 ± 11.2 vs 95.7 ± 17.1 (P < .05). No complications with regard to wound healing or infection were noted. Twelve relatively young patients returned to preinjury activity levels, such as playing basketball or badminton, and the older patients were able to meet their daily needs, such as walking up stairs and jogging. CONCLUSION: Chronic AT ruptures were successfully treated via minimally invasive reconstruction using a double-bundle FHL, which provided excellent functional improvement. It is best suited for patients with complex requirements who are at high risk for wound complications.