OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective To evaluate the efficacy and safety of a novel gastrointestinal mucosal elevation gel in vivo porcine model. Methods Eight healthy white pigs were selected, which were uesd to bump height evaluation (n=2) and safety evaluation (n=6). The sample (alimentary canal mucosa bump gel sample) and the control sample (disposable endoscopic submucosal filler of alimentary canal) were respectively injected into the submucosa of pig gastric antrum and gastric body. In the evaluation of elevation height, the morphology, persistence, and clinical safety of mucosal elevation were observed and recorded immediately and 30 minutes after injection. In safety evaluation, endoscopic mucosal resection was performed after injection, and the mucosal protrusion shape, product efficacy, and clinical safety were observed and recorded at immediate and 7-day time points. After observation, all animals were euthanized and tissue samples were collected and excised for histopathological evaluation. Results In elevation height evaluation, sample group showed a steep elevation immediately after surgery, exhibiting a more pronounced elevation morphology compared to control group (P=0.019). Only two (25%) sites of the elevation showed slight collapse in 30 minutes after surgery, and the durability notably increased compared to control group (8 all collapsed, P＜0.001). In safety evaluation, the average trauma area of sample group was 1.77 mm², which was significantly lower than control group (2.65 mm², P＜0.001). There was no statistical difference among average injection dose per unit area, surgical time per unit area, and en bloc resection rate. Sample group showed mild ulcers and only 1 (12.5%) site of mild bleeding at immediate time point after surgery. No bleeding, perforation, ulcer or edema was observed in sample group 7 days after surgery, and no statistical difference was identified compared to control group. Histopathological evaluation found that the gastric antrum and body tissues exhibited moderate injury and mild edema at immediate time point, accompanied by mild inflammatory cellular infiltration. At 7-day time point, gastric antrum tissues demonstrated moderate injury, mild edema and mild inflammatory cellular infiltration, with 1 (12.5%) site of tissues infected, while in gastric body tissues, no bleeding was observed, whereas moderate injury and mild edema were evident, accompanied by mild inflammatory cellular infiltration and 3 (37.5%) sites of tissues infected, all of which were not statistically different from control group. Conclusion The novel gastrointestinal mucosal elevation gel exhibited steep elevation morphology, long-lasting elevation height, and favorable efficacy and safety in preclinical animal trials, showing enormous clinical application potential.

Objective: To study the positive effect and mechanism of histone deacetylase Sirtuin 1 (Sirt1) on the osteogenic capacity of inflammatory PDLSCs. Methods: PDLSCs were isolated and cultured from the healthy individuals and periodontitis patients , the expression of Sirt1 in two types of PDLSCs was observed;osteogenic induction of inflammatory PDLSCs was performed , concurrently Sirt1 agonist resveratrol was used to up⁃regulate the expression of Sirt1 , then the osteogenic differentiation was observed , the expressions of Runx2 , acetylated NF⁃κB , acetylated FoxO1 and FoxO1 were assessed by Western blot. Results : The protein expression of Sirt1 was suppressed in in flamed PDLSCs( P < 0. 01) ;resveratrol could up⁃regulate the expression of Sirt1 in inflamed PDLSCs;compared with the osteogenic induction group , the osteogenesis + resveratrol group increased the expression of BSP ( t =14. 045 ,P < 0. 01) , Runx2( t = 3. 349 ,P < 0. 01) , OCN( t = 7. 218 ,P < 0. 01) and Osx ( t = 4. 544 ,P < 0. 01) mRNA in inflamed PDLSCs , and enhanced ALP staining(P < 0. 01) ;expression of FoxO1( t = 8. 737 , P < 0. 01) and Runx2( t = 6. 152 , P < 0. 01) increased after osteogenesis of inflamed PDLSCs ; in the osteogenesis + resveratrol group , the expression of Sirt1 was up⁃regulated , and the expression of FoxO1( t = 5. 912 ,P < 0. 01) and Runx2( t =6. 277 ,P < 0. 01) further increased compared with the osteogenic induction group ,while the expression of acetylated NF⁃κB(F = 184. 033 ,P < 0. 01) and acetylated FoxO1(F = 301. 454 , P < 0. 01) was significantly lower than that of control group and osteogenic induction group. Conclusion The deacetylase Sirt1 could promote the osteogenic differentiation of inflammatory PDLSCs through deacetylating NF⁃κB and FoxO1 .

Objective: To study the mechanism of Pirfenidone (PFD) inhibiting the invasion of biliary tract tumors through cancer associated fibroblasts ( CAF) ． Methods: Primary CAF were extracted from the tumor tissues of patients with biliary tract tumor，and the marker proteins of CAF，including vimentin (VIM) ，α-smooth muscle actin ( α-SMA) and fibroblast activating protein ( FAP) were detected by Western blot．Phalloidin experiment showed the function of fibroblast cytoskeleton．ELISA and Western blot were used to verify the difference of TGF-β expression between normal fibroblasts ( NF) and CAF．The functional change of CAF was observed by adding PFD to CAF．The expression of TGF-β in CAF was verified by ELISA，quantitative real-time PCR (qRT-PCR) and Western blot．The change of TGF-β in serum was verified by subcutaneous tumor mouse model．The change of collagen contractile function in CAF was observed by collagen contractile test．The changes of MMP2 and MMP9 in CAF medium were observed by gelatin enzyme assay．The changes of SMAD signaling pathway protein in CAF were detected by Western blot. Results : The related marker proteins VIM，α-SMA and FAP of CAF were highly expressed， and the filamentous actin (F-actin) of CAF was abundant．ELISA showed that the expression of TGF-β in CAF was enhanced．Western blot experiment confirmed that CAF had stronger collagen function．Western blot，PCR and related phenomenon experiments showed that PFD could inhibit collagen production and TGF-β expression in CAF. SMAD signaling pathway-related protein experiments demonstrated that PFD could affect tumor invasion by inhibiting TGF-β/ SMAD signaling pathway． Conclusion The function of CAF extracted from cancer patients is dominated by collagen production，while PFD inhibits the collagen production and collagen remodeling related processes of CAF through TGF-β/ SMAD signaling pathway to inhibit tumor invasion.

Objective : To study the mechanism of Pirfenidone (PFD) inhibiting the invasion of biliary tract tumors through cancer associated fibroblasts ( CAF) ． Methods : Primary CAF were extracted from the tumor tissues of patients with biliary tract tumor，and the marker proteins of CAF，including vimentin (VIM) ，α-smooth muscle actin ( α-SMA) and fibroblast activating protein ( FAP) were detected by Western blot．Phalloidin experiment showed the function of fibroblast cytoskeleton．ELISA and Western blot were used to verify the difference of TGF-β expression between normal fibroblasts ( NF) and CAF．The functional change of CAF was observed by adding PFD to CAF．The expression of TGF-β in CAF was verified by ELISA，quantitative realtime PCR (qRT-PCR) and West- ern blot．The change of TGF-β in serum was verified by subcutaneous tumor mouse model．The change of collagen contractile function in CAF was observed by collagen contractile test．The changes of MMP2 and MMP9 in CAF me- dium were observed by gelatin enzyme assay．The changes of SMAD signaling pathway protein in CAF were detec- ted by Western blot. Results : The related marker proteins VIM，α-SMA and FAP of CAF were highly expressed， and the filamentous actin (F-actin) of CAF was abundant．ELISA showed that the expression of TGF-β in CAF was enhanced．Western blot experiment confirmed that CAF had stronger collagen function．Western blot，PCR and related phenomenon experiments showed that PFD could inhibit collagen production and TGF-β expression in CAF. SMAD signaling pathway-related protein experiments demonstrated that PFD could affect tumor invasion by inhibi- ting TGF-β/ SMAD signaling pathway Conclusion The function of CAF extracted from cancer patients is dominated by collagen production，while PFD inhibits the collagen production and collagen remodeling related processes of CAF through TGF-β/ SMAD signaling pathway to inhibit tumor invasion.

Lower limb ankle exoskeletons have been used to improve walking efficiency and assist the elderly and patients with motor dysfunction in daily activities or rehabilitation training, while the assistance patterns may influence the wearer's lower limb muscle activities and coordination patterns. In this paper, we aim to evaluate the effects of different ankle exoskeleton assistance patterns on wearer's lower limb muscle activities and coordination patterns. A tethered ankle exoskeleton with nine assistance patterns that combined with differenet actuation timing values and torque magnitude levels was used to assist human walking. Lower limb muscle surface electromyography signals were collected from 7 participants walking on a treadmill at a speed of 1.25 m/s. Results showed that the soleus muscle activities were significantly reduced during assisted walking. In one assistance pattern with peak time in 49% of stride and peak torque at 0.7 N·m/kg, the soleus muscle activity was decreased by (38.5 ± 10.8)%. Compared with actuation timing, the assistance torque magnitude had a more significant influence on soleus muscle activity. In all assistance patterns, the eight lower limb muscle activities could be decomposed to five basic muscle synergies. The muscle synergies changed little under assistance with appropriate actuation timing and torque magnitude. Besides, co-contraction indexs of soleus and tibialis anterior, rectus femoris and semitendinosus under exoskeleton assistance were higher than normal walking. Our results are expected to help to understand how healthy wearers adjust their neuromuscular control mechanisms to adapt to different exoskeleton assistance patterns, and provide reference to select appropriate assistance to improve walking efficiency.
Aged ; Ankle/physiology* ; Ankle Joint/physiology* ; Biomechanical Phenomena/physiology* ; Electromyography ; Exoskeleton Device ; Gait/physiology* ; Humans ; Muscle Contraction ; Muscle, Skeletal/physiology* ; Walking/physiology*

Objective:To develop a set of algorithms that could predict the precise size of acetabular cup preoperatively by the deep learning neural network technology.Methods:Retrospective analysis was performed on 30 patients with femoral head necrosis from April 2019 to April 2020, including 15 males and 15 females. At the age of (54.8±10.5) years (range 33-72 years). Thirteen hips on the left and seventeen hips on the right, who underwent primary unilateral THA. Based on the manually segmented hip joint CT database, a deep learning convolutional neural network was trained to realize automatic segmentation. A customized algorithm was created to fit the surface of the acetabulum. By the application of another deep learning convolutional neural network, the identification of anatomical points of the pelvis and correction of the pelvic position were realized. So that the placement of the acetabulum cup could be done. DOC (dice overlap coefficients) as well as the average error parameter were adopted to evaluate the accuracy of the above steps. The novel algorithm and Orthoview software were retrospectively used to template the acetabular cup separately. The results of both groups were compared with the actual size and the coincidence rate was calculated to evaluate the accuracy of the novel algorithm. To verify this algorithm, the conformance rate was calculated respectively.Results:Compared with other classical segmentation networks, the G-NET network can segment the pelvic with femoral head necrosis more accurately (DOC 92.51%± 6.70%). It also has better robustness. The average error of the point recognition network is 0.87 pixels. Among the 30 patients, the AI-based algorithm group had a complete coincidence rate of 96.7% and the Orthoview group had a complete coincidence rate of 73.3%. The difference was statistically significant ( χ2=6.405, P=0.011). Conclusion:The artificial intelligence-based algorithm can segment the CT image series and identify the feature points of the patient's hip accurately. Compared with the conventional 2D preoperative planning method, the AI-based algorithm is relatively more accurate. This artificial intelligence-based 3D preoperative software has promising prospect to makeaccurate surgical plan efficiently.

OBJECTIVE：To compare the protective effects of different effective components of Astragali radix against DNA damage of human bone marrow mesenchymal stem cells （BMSCs）induced by ionizing radiation. METHODS ：2 Gy X-rays were used to directly irradiate BMSCs to establish a radiation model. CCK- 8 method was used to detect the effects of different mass concentrations（25，50，75，100 μg/mL）of astragalus polysaccharide ，astragalus saponin and astragalus flavonoids for 1 day before radiation + 1 to 5 days after radiation on the proliferation of BMSCs. The dose concentration and the duration of intervention after radiation were selected. The irradiated BMSCs were divided into radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group. The last three groups were treated with appropriate dosage of corresponding drugs before and 2 days after radiation ，and a blank groupwas set for comparison. Cytoplasmic division arrest qq.com micronucleus method was used to detect micronucleus cell rate and cell micronucleus rate after appropriate time of was used to detect th e number of 53BP1 foci in cells after appropriare time of intervention following radiation ；the number of 53BP1 foci were compared among different time points （0.5，2，12，24 h）. RESULTS ：Compared with blank group ，OD values of BMSCs were decreased significantly in radiation group （P＜0.05 or P＜0.01）. Compared with radiation group ，the OD values of BMSCs were significantly increased when 50 μ g/mL astragalus polysaccharide，astragalus saponin and astragalus flavonoids continuously intervened radiation for 2-3 days，there was significant difference in other groups at some time point （P＜0.05 or P＜ 0.01）. After consideration ，drug concentration was determined to be 50 μg/mL，and the continuous intervention time was 2 days after radiation. Compared with blank group ，the micronucleus cell rate and cell micronucleus rate of radiation group ，astragalus polysaccharide group ，astragalus saponin group and astragalus flavonoids group increased significantly ，and the number of 53BP1 focus cluster in radiation group and astragalus polysaccharide group increased significantly （P＜0.01）. Compared with radiation group and astragalus flavonoids group ，the micronucleus cell rate ，cell micronucleus rate and the number of 53BP1 focus cluster （continued intervention for 0.5，2，12 h）in the astragalus polysaccharide group and astragalus saponin group were significantly reduced，and the micronucleus cell rate and cell micronucleus rate in the astragalus polysaccharide group were significantly lower than astragalus saponin group （P＜0.05）. 53BP1 focus cluster could not be detected 24 h later （P＜0.05）. CONCLUSIONS ： Astragalus polysaccharide and astragalus saponin both have protective effects on BMSCs DNA damage induced by radiation ，and the protective effect of astragalus polysaccharide is better than that of astragalus saponin ；astragalus flavonoids has no protective effect on radiation-induced DNA damage.

In many pathogens infection,especially virus,antibody-dependent enhancement(ADE) can aggravate the infection and lead to severe diseases.In this immunopathological phenomenon,virus-specific antibodies enhance the entry of virus into monocytes,macrophages and granulocytic cells and even the replication of virus through different mechanism.This phenomenon has been reported in numerous pathogens including virus,bacteria and parasite and the mechanisms of ADE vary from different species.Further study of ADE can promote the vaccine research and development to make the most use of vaccine and prevent human body from pathogens,which will be helpful to control the spread of pathogens including Zika virus.In the present review,we review the research progress of ADE mechanism in recent years,including antibodies mediating,receptors mediating,complement mediating,viral proteins mediating and cellular mediating ADE.In addition,dengue virus,human immunodeficiency virus,Coxsackie virus,Ebola virus,Zika virus and other pathogens will be illustrated respectively.This review provides insights on the different mechanism of ADE in different pathogens.