Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective:To observe the early clinical efficacy of 3D-printed modular supporting prosthesis for reconstruction of lacunar bone defect caused by giant cell tumor of the distal femur.Methods:From May 2018 to July 2023, a total of 9 patients with giant cell tumor of the distal femur were treated with 3D-printed modular supporting prosthesis to reconstruct lacunar bone defects in the Department of Orthopedics, West China Hospital, Sichuan University. There were 4 males and 5 females, aged 30.8±6.1 years (range, 24-44 years), 5 cases on the left side, 4 cases on the right side, 2 cases of Campanacci grade I, 7 cases of Campanacci grade II. The anteroposterior and lateral X-ray films and T-SMART tomosynthesis imaging of the knee joint were taken to observe the bone graft healing and osseointegration after operation. Musculoskeletal Tumor Society (MSTS)-93 was used to evaluate knee function, and visual analogue scale (VAS) was used to evaluate knee pain.Results:All patients were successfully operated and followed up for an average of 30.8±7.5 months (range, 18-42 months). The operation time was 124.2±23.6 min, and the intraoperative blood loss was 105.6±17.4 ml. All autografts showed bony union at the graft-host junction, and the healing time was 3.3±0.4 months (range, 3.0-4.0 months). At 6 months after surgery, T-SMART tomosynthesis imaging showed that the gap between the prosthesis-bone interface was less than 1 mm in all patients. At the last follow-up, the thickness of residual subchondral bone was 5.7±1.3 mm, which was greater than that before operation 2.2±0.8 mm, and the difference was statistically significant ( t=10.823, P<0.001). At the last follow-up, the score of MSTS-93 was 26.7±2.4, which was higher than that before operation 18.8±3.7, and the difference was statistically significant ( t=5.367, P<0.001). At the last follow-up, the range of motion of the knee joint was 122.8°±9.1°, which was higher than that before operation 108.3°±6.1°, and the difference was statistically significant ( t=3.970, P<0.001). All patients were able to walk normally, go up and down stairs and other daily activities, and 7 patients were able to complete squats. At the last follow-up, there was no local tumor recurrence, distant metastasis, death, joint infection, pain (VAS score was 0), delayed wound healing, joint degeneration, prosthesis loosening or articular surface collapse. Conclusion:Reconstruction of lacunar bone defect caused by giant cell tumor of distal femur with 3D-printed modular supporting prosthesis can effectively improve knee joint function and osseointegration, and the short-term clinical results are satisfactory.

Objective:To explore the early and mid-term efficacy of three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee.Methods:A retrospective analysis was conducted on the data of 24 patients who underwent reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee using 3D-printed customized porous prostheses at West China Hospital of Sichuan University from June 2015 to June 2021. There were 14 female cases and 10 male cases, with an average age of 28.9±16.5 years (range, 12-61 years), 12 cases at the distal end of the femur and 12 cases at the proximal end of the tibia. Tumor types: 16 cases of osteosarcoma, 4 cases of Ewing's sarcoma, 2 cases of chondrosarcoma, and 2 case of parosteal osteosarcoma. All patients were classified as Enneking stage IIB. Record the oncology results of the patients, the length of tumor segment resection, and the remaining bone length at the distal femur or proximal tibia, as well as complications, systemic metastasis and imaging changes. The bone integration at the prosthesis-bone interface was evaluated by tomosynthesis-shimadzu metal artifact reduction technology (T-SMART). Limb function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score and knee range of motion assessment.Results:All 24 patients successfully completed the surgery and were followed up, with an average follow-up time of 51.8±12.7 months (range, 32-99 months). The length of femoral osteotomy was 241.1±66.2 mm (range, 150.6-333.4 mm), and the length of tibial osteotomy was 198.6±35.6 mm (range, 156.6-287.6 mm). The remaining bone length at the epiphyseal end around the knee joint (from the knee joint plane to the osteotomy plane of the distal femur or proximal tibia) was 52.6±11.0 mm (range, 31.1-77.5 mm). At the last follow-up, 23 patients survived tumor-free, while one patient died due to lung metastasis 54 months after the operation. One patient had prosthesis fracture 75 months after the operation, two patients had aseptic loosening 6 and 8 months after the operation, and the T-SMART of the remaining 20 patients showed that the implanted prostheses all achieved good osseointegration. At the last follow-up, the range of motion of the knee joint was 126.2°±7.5° (range, 110.0°-140.0°), and the MSTS-93 score was 26.7±1.8 points (range, 23-30 points). Among them, the MSTS-93 score of the femoral prosthesis was 26.7±1.6 points (range, 24-29 points), and the MSTS-93 score of the tibial prosthesis was 26.9±1.9 points (range, 23-30 points). The average knee range of motion was 126.2°±7.5° (range, 110°-140°), and the MSTS-93 functional score was 26.7±1.8 points (range, 23-30 points) at the last follow-up. The femoral component had an average score of 26.7±1.6 points (range, 24-29 points), while the tibial component had an average score of 26.9±1.9 points (range, 23-30 points).Conclusion:The application three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee can preserve the joint, restore limb function well, and have a low incidence of prosthesis complications, with good clinical efficacy in the early and middle stages.

Objective:To observe the early clinical efficacy of 3D-printed modular supporting prosthesis for reconstruction of lacunar bone defect caused by giant cell tumor of the distal femur.Methods:From May 2018 to July 2023, a total of 9 patients with giant cell tumor of the distal femur were treated with 3D-printed modular supporting prosthesis to reconstruct lacunar bone defects in the Department of Orthopedics, West China Hospital, Sichuan University. There were 4 males and 5 females, aged 30.8±6.1 years (range, 24-44 years), 5 cases on the left side, 4 cases on the right side, 2 cases of Campanacci grade I, 7 cases of Campanacci grade II. The anteroposterior and lateral X-ray films and T-SMART tomosynthesis imaging of the knee joint were taken to observe the bone graft healing and osseointegration after operation. Musculoskeletal Tumor Society (MSTS)-93 was used to evaluate knee function, and visual analogue scale (VAS) was used to evaluate knee pain.Results:All patients were successfully operated and followed up for an average of 30.8±7.5 months (range, 18-42 months). The operation time was 124.2±23.6 min, and the intraoperative blood loss was 105.6±17.4 ml. All autografts showed bony union at the graft-host junction, and the healing time was 3.3±0.4 months (range, 3.0-4.0 months). At 6 months after surgery, T-SMART tomosynthesis imaging showed that the gap between the prosthesis-bone interface was less than 1 mm in all patients. At the last follow-up, the thickness of residual subchondral bone was 5.7±1.3 mm, which was greater than that before operation 2.2±0.8 mm, and the difference was statistically significant ( t=10.823, P<0.001). At the last follow-up, the score of MSTS-93 was 26.7±2.4, which was higher than that before operation 18.8±3.7, and the difference was statistically significant ( t=5.367, P<0.001). At the last follow-up, the range of motion of the knee joint was 122.8°±9.1°, which was higher than that before operation 108.3°±6.1°, and the difference was statistically significant ( t=3.970, P<0.001). All patients were able to walk normally, go up and down stairs and other daily activities, and 7 patients were able to complete squats. At the last follow-up, there was no local tumor recurrence, distant metastasis, death, joint infection, pain (VAS score was 0), delayed wound healing, joint degeneration, prosthesis loosening or articular surface collapse. Conclusion:Reconstruction of lacunar bone defect caused by giant cell tumor of distal femur with 3D-printed modular supporting prosthesis can effectively improve knee joint function and osseointegration, and the short-term clinical results are satisfactory.

Objective:To explore the early and mid-term efficacy of three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee.Methods:A retrospective analysis was conducted on the data of 24 patients who underwent reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee using 3D-printed customized porous prostheses at West China Hospital of Sichuan University from June 2015 to June 2021. There were 14 female cases and 10 male cases, with an average age of 28.9±16.5 years (range, 12-61 years), 12 cases at the distal end of the femur and 12 cases at the proximal end of the tibia. Tumor types: 16 cases of osteosarcoma, 4 cases of Ewing's sarcoma, 2 cases of chondrosarcoma, and 2 case of parosteal osteosarcoma. All patients were classified as Enneking stage IIB. Record the oncology results of the patients, the length of tumor segment resection, and the remaining bone length at the distal femur or proximal tibia, as well as complications, systemic metastasis and imaging changes. The bone integration at the prosthesis-bone interface was evaluated by tomosynthesis-shimadzu metal artifact reduction technology (T-SMART). Limb function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score and knee range of motion assessment.Results:All 24 patients successfully completed the surgery and were followed up, with an average follow-up time of 51.8±12.7 months (range, 32-99 months). The length of femoral osteotomy was 241.1±66.2 mm (range, 150.6-333.4 mm), and the length of tibial osteotomy was 198.6±35.6 mm (range, 156.6-287.6 mm). The remaining bone length at the epiphyseal end around the knee joint (from the knee joint plane to the osteotomy plane of the distal femur or proximal tibia) was 52.6±11.0 mm (range, 31.1-77.5 mm). At the last follow-up, 23 patients survived tumor-free, while one patient died due to lung metastasis 54 months after the operation. One patient had prosthesis fracture 75 months after the operation, two patients had aseptic loosening 6 and 8 months after the operation, and the T-SMART of the remaining 20 patients showed that the implanted prostheses all achieved good osseointegration. At the last follow-up, the range of motion of the knee joint was 126.2°±7.5° (range, 110.0°-140.0°), and the MSTS-93 score was 26.7±1.8 points (range, 23-30 points). Among them, the MSTS-93 score of the femoral prosthesis was 26.7±1.6 points (range, 24-29 points), and the MSTS-93 score of the tibial prosthesis was 26.9±1.9 points (range, 23-30 points). The average knee range of motion was 126.2°±7.5° (range, 110°-140°), and the MSTS-93 functional score was 26.7±1.8 points (range, 23-30 points) at the last follow-up. The femoral component had an average score of 26.7±1.6 points (range, 24-29 points), while the tibial component had an average score of 26.9±1.9 points (range, 23-30 points).Conclusion:The application three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee can preserve the joint, restore limb function well, and have a low incidence of prosthesis complications, with good clinical efficacy in the early and middle stages.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

OBJECTIVE: To evaluate the feasibility and short-term effectiveness of three-dimensional (3D)-printed customized porous acetabular components for reconstruction of extensive acetabular bone defects during primary total hip arthroplasty (THA). METHODS: The clinical data of 8 patients with extensive acetabular bone defects, who were treated with 3D-printed individualized porous acetabular components between July 2018 and January 2022, were retrospectively analyzed. The cohort comprised 4 males and 4 females with an average age of 48 years ranging from 34 to 56 years. Acetabular bone defects were classified as Paprosky type ⅢA in 3 cases and type ⅢB in 5 cases. The causes of acetabular destruction were hip tuberculosis (5 cases), pigmented villonodular synovitis (2 cases), and syphilitic arthritis (1 case). Visual analogue scale (VAS) score and Harris hip score (HHS) were used to evaluate the pain relief and hip function before and after operation. Reconstruction outcomes were further assessed by imaging results [X-ray film and Tomosynthesis Shimadzumetal artefact reduction technology (T-SMART)], and the mechanical properties were evaluated by finite element analysis. RESULTS: The operation time ranged from 174 to 195 minutes (mean, 187 minutes), and intraoperative blood loss ranged from 390 to 530 mL (mean, 465 mL). All 8 patients were follow-up 26-74 months (mean, 44 months). Among the 5 patients with tuberculosis, none experienced postoperative recurrence. At last follow-up, the VAS score was 0.3±0.5 and the HHS score was 87.9±3.7, both significantly improved compared to preoperative values ( t=25.170, P<0.001; t=-28.322, P<0.001). X-ray films at 2 years after operation demonstrated satisfactory matching between the 3D-printed customized acetabular component and the acetabulum. The postoperative center of rotation of the operated hip was shifted by (2.1±0.5) mm horizontally and (2.0±0.7) mm vertically relative to the contralateral side, with both offsets showing significant differences compared to preoperative values ( t=24.700, P<0.001; t=55.230, P<0.001). T-SMART imaging showed satisfactory osseointegration at the implant-host bone interface. No complications such as aseptic loosening or screw breakage was observed during follow-up. Finite element analysis showed that the acetabular component had good mechanical properties. CONCLUSION The application of 3D-printed individualized porous acetabular components in the reconstruction of extensive acetabular bone defects demonstrated precise anatomical reconstruction, stable mechanical support, and good functional performance in short-term follow-up, offering a potential alternative for acetabular defect reconstruction in primary THA.
Humans ; Middle Aged ; Male ; Female ; Printing, Three-Dimensional ; Arthroplasty, Replacement, Hip/instrumentation* ; Acetabulum/diagnostic imaging* ; Adult ; Follow-Up Studies ; Retrospective Studies ; Hip Prosthesis ; Prosthesis Design ; Porosity ; Treatment Outcome ; Plastic Surgery Procedures/methods*