The tumorigenic effect of the high expression of ABRACL in glioma and its potential as a therapeutic target.

Gliomas are the most common malignant intracranial tumors, with no effective treatments. Better understanding and identification of novel targets are urgently warranted. Actin-binding Rho activating C-terminal like (ABRACL) has been reported as an oncogene in several cancer types. However, the potential roles of ABRACL in the tumorigenesis of malignant glioma remain unknown. We discovered that ABRACL is highly expressed in different sub-types of gliomas in both CGGA and TCGA databases, which was further validated in glioblastoma cell lines and normal human astrocyte lines. RT-qPCR, Western blotting and immunohistochemistry demonstrated that ABRACL expression in glioma tissues was upregulated along with the increasing WHO grades. Further survival analysis of glioma patients also revealed that the overall survival of patients in the ABRACL high expression level group were significantly shorter than those in the low expression level group. Knockdown of ABRACL inhibited the proliferation, cell migration, invasion and cytodynamics behaviors in glioma cell lines via activating STAT3 signaling, which also induced apoptosis and cell cycle arrest. Conversely, overexpressing ABRACL promoted cell renewing and migration, enabled more flexible cell deformation, supporting ABRACL being a bona fide oncogene. Intracranial orthotopic xenograft experiment further confirmed that ABRACL downregulation significantly suppressed glioma growth. These results have demonstrated that the tumorigenic effect of ABRACL is partly mediated by STAT3, whose expression also correlates with clinical prognosis. ABRACL facilitates glioma malignancy phenotype through regulating the cytoskeleton by activating STAT3 pathway, suggesting that it may represent a potential therapeutic target for glioblastoma.

SVIL promotes ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions through the TGF-ß/Smad pathway.

OBJECTIVE: Ovarian cancer is the malignant tumor with the highest mortality rate in gynecology. We aimed to identify novel genes that promote ovarian cancer progression and epithelial-mesenchymal transition under hypoxic conditions. METHODS: We screened SVIL as a hypoxia-associated target in ovarian cancer and explored the related molecular mechanisms. We assessed the effects of SVIL on ovarian cancer progression and metastasis in clinical samples and cellular hypoxia models. Further, we investigated the relevant pathways of SVIL and confirmed the effects of SVIL on ovarian cancer progression by using nude mouse in situ tumor models. RESULTS: We found that SVIL was significantly highly expressed in the hypoxic environment of ovarian cancer, and SVIL expression correlated with patient prognosis.CCK8, Wound-healing assay, Transwell assay, Western Blot, and apoptosis assays revealed that knockdown of SVIL inhibited the activation of the TGFß1/smad2/3 pathway, which attenuated the progression and epithelial-mesenchymal transition(EMT) of ovarian cancer and alleviated cisplatin resistance by increasing cisplatin-induced apoptosis. Furthermore, in a nude mouse ovarian cancer in situ model, we found that the knockdown of SVIL significantly inhibited tumor growth and metastasis. CONCLUSION: SVIL highly expressed in the hypoxic microenvironment can increase ovarian cancer progression and cisplatin resistance by activating TGFß1/smad2/3 pathway. Our study demonstrated that SVIL may be a novel target for the treatment of ovarian cancer.

The performance of a combination of heparin-binding protein with other biomarkers for sepsis diagnosis: an observational cohort study.

BACKGROUND: HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers. METHODS: Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis. RESULTS: A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p < 0.05) observed for all parameters. When compared to SOFA score and traditional markers of CRP, PCT, IL-6 and IL-8, the combined indexes of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB demonstrated significantly improved diagnostic performance for sepsis and septic shock (AUC 0.911 and 0.902 respectively, p < 0.001). CONCLUSIONS: The combined measurements of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB can augment the diagnostic capacity of HBP for sepsis, and offer reliable early supplementary indicators to traditional biomarkers for assessing disease severity in patients with infection.

The prognostic impact of tumor location in nonmuscle-invasive bladder cancer patients undergoing transurethral resection: insights from a cohort study utilizing Chinese multicenter and SEER registries.

OBJECTIVE: Most bladder cancers are nonmuscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach. METHODS: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias. RESULTS: This study included 118 477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 ( P <0.0001); RFS of 2.21 ( P <0.0001); SEER cohort OS HR of 1.10 ( P =0.0001); DSS HR of 1.13 ( P =0.0183). Dome tumors displayed similar trends [Chinese NMIBC cohort OS HR of 7.91 ( P <0.0001); RFS HR of 2.12 ( P <0.0001); SEER OS HR of 1.05 ( P =0.0087); DSS HR of 1.14 ( P =0.0006)]. Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment ( P <0.01). CONCLUSION: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

SECTM1 promotes the development of glioblastoma and mesenchymal transition by regulating the TGFß1/Smad signaling pathway.

Objective: Secreted and transmembrane protein 1 (SECTM1) is a gene encoding a transmembrane protein. The role of SECTM1 in glioblastoma (GBM) is unclear. Here, we reported the abnormal expression of SECTM1 in GBM for the first time and studied the role and mechanism of SECTM1 in GBM. Methods: qRT-PCR, Western blotting and immunofluorescence were used to detect the expression of SECTM1 in gliomas of different grades and GBM cell lines. After the knockdown of SECTM1 expression in cell lines by shRNA, the effect of SECTM1 in GBM cell lines was verified by CCK-8, Transwell, EdU and wound healing experiments. We further investigated the effect and mechanism of SECTM1 on GBM in vitro and in vivo. The effect of SECTM1 on glioma growth was detected by subcutaneous tumor xenografts in nude mice in vivo. Results: The results showed that the knockdown of SECTM1 expression in cell lines significantly inhibited the proliferation, migration and invasion of GBM cells while inhibiting the progression of subcutaneous xenograft tumors in nude mice. However, the role and molecular mechanism of SECTM1 in GBM remain unclear. SECTM1 was found to promote GBM epithelial-mesenchymal transition (EMT) like processes. Bioinformatics analysis and Western blotting showed that SECTM1 regulates glioblastoma invasion and EMT-like processes mainly through the TGFß1/Smad signaling pathway. Conclusion: The low expression of SECTM1 has an inhibitory effect on GBM and is a potential target for GBM treatment. SECTM1 may also be a promising biomarker for the diagnosis and prognosis of GBM.

[Application of Nice knot technique in wound closure of Gustilo type â ¢A and â ¢B open tibial fractures].

Objective: To explore the effectiveness of Nice knot technique for wound closure in Gustilo type ⅢA and ⅢB open tibial fractures. Methods: A retrospective study was performed on 22 patients with Gustilo type ⅢA and ⅢB open tibial fractures, who underwent wound closure using the Nice knot technique and were admitted between June 2021 and June 2022. There were 15 males and 7 females. The age ranged from 18 to 67 years, with an average of 41.9 years. The causes of injury included traffic accident in 11 cases, falling from height in 7 cases, and heavy object injuries in 4 cases. Fractures were located on the left side in 9 cases and on the right side in 13 cases. And 9 cases were type ⅢA fractures and 13 were type ⅢB fractures according to Gustilo classification. All patients had extensive soft tissue injuries, and no vascular or neurological damage was observed. The time from injury to debridement was 3-8 hours (mean, 6.5 hours). The sizes of wounds before operation and at 2 weeks after operation were measured and wound healing rate at 2 weeks after operation were calculated. The wound healing time and wound healing grading were recorded. The Vancouver Scar Scale (VSS) score was used to assess the wound scar after wound healed and the excellent and good rate was calculated. Results: The wound area was 21.0-180.0 cm 2 (mean, 57.82 cm 2) before operation, and it was 1.2-27.0 cm 2 (mean, 6.57 cm 2) at 2 weeks after operation. The wound healing rate at 2 weeks after operation was 76%-98% (mean, 88.6%). After operation, 2 cases needed to adjust Nice knot due to skin cutting and 1 case occurred soft tissue infection on the wound. The other patient's wounds healed. The average wound healing time was 27.8 days (range, 18-44 days). And the wound healing were grade A in 13 cases and grade B in 9 cases. VSS score was 2-9, with an average of 4.1; 10 cases were rated as excellent, 10 as good, and 2 as poor, with an excellent and good rate of 90.9%. All patients were followed up 9-24 months (mean, 14.6 months). During follow-up, no deep infection or osteomyelitis occurred. Two cases experienced fracture non-union, and were treated with compression fixation and bone grafting. The fractures of the other patients all healed, with a healing time of 85-190 days (mean, 148.2 days). Conclusion: Nice knot technique can be used in wound closure of Gustilo type ⅢA and ⅢB open tibial fractures effectively, which is easy to operate.

Hollow Cu2MoS4 nanoparticles loaded with immune checkpoint inhibitors reshape the tumor microenvironment to enhance immunotherapy for pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that responds poorly to single-drug immunotherapy with PD-L1 (CD274) inhibitors. Here, we prepared mesoporous nanomaterials Cu2MoS4 (CMS)/PEG loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. In vitro experiments, CMS/PEG-B-P have a more substantial inhibitory effect on the expression of PD-L1 and CXCR4 as well as to promote the apoptosis of pancreatic cancer cells KPC and suppressed KPC cell proliferation were detected by flow cytometry, qPCR and Western blotting (WB). Promotes the release of the cytotoxic substance reactive oxygen species (ROS) and the production of the immunogenic cell death (ICD) marker calreticulin (CRT) in KPC cells. CMS/PEG-B-P was also detected to have a certain activating effect on mouse immune cells, dendritic cells (mDC) and macrophage RAW264.7. Subcutaneous tumorigenicity experiments in C57BL/6 mice verified that CMS/PEG-B-P had an inhibitory effect on the growth of tumors and remodeling of the tumor immune microenvironment, including infiltration of CD4+ and CD8+ T cells and polarization of macrophages, as well as reduction of immunosuppressive cells. Meanwhile, CMS/PEG-B-P was found to have different effects on the release of cytokines in the tumor immune microenvironment, including The levels of immunostimulatory cytokines INF-γ and IL-12 are increased and the levels of immunosuppressive cytokines IL-6, IL-10 and IFN-α are decreased. In conclusion, nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach. STATEMENT OF SIGNIFICANCE: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that has a low response to single-drug immunotherapy with PD-L1 (CD274) inhibitors. We preared PEG-modified mesoporous nanomaterials Cu2MoS4 (CMS) loaded with PD-L1 inhibitor BMS-1 and CXCR4 inhibitor Plerixafor to form the nanodrug CMS/PEG-B-P. Our study demonstrated that Nanomaterial-loaded immune checkpoint inhibitor therapies can enhance the immune response and reduce side effects, a combination that shows great potential as a new immunotherapeutic approach.

Identification and validation of a novel necroptosis-related molecular signature to evaluate prognosis and immune features in breast cancer.

Necroptosis has been shown to play an important role in the development of tumors. However, the characteristics of the necroptosis-related subtypes and the associated immune cell infiltration in the tumor microenvironment (TME) of breast cancer (BRCA) remain unclear. In this study, we identified three clusters related to necroptosis using the expression patterns of necroptosis-relevant genes (NRGs), and found that these three clusters had different clinicopathological features, prognosis and immune cell infiltration in the TME. Cluster 2 was characterized by less infiltration of immune cells in the TME and was associated with a worse prognosis. Then, a necroptosis risk score (NRS) composed of 14 NRGs was constructed using the least absolute shrinkage and selection operator regression (LASSO) Cox regression method. Based on NRS, all BRCA patients in the TCGA datasets were classified into a low-risk group and a high-risk group. Patients in the low-risk group were characterized by longer overall survival (OS), lower mutation burden, and higher infiltration level of immune cells in the TME. Moreover, the NRS was significantly associated with chemotherapeutic drug sensitivity. Finally, the knockdown of VDAC1 reduced the proliferation and migration of BRCA cells, and promoted cell death induced by necroptosis inducer. This study identified a novel necroptosis-related subtype of BRCA, and a comprehensive analysis of NRGs in BRCA revealed its potential roles in prognosis, clinicopathological features, TME, chemotherapy, tumor proliferation, and tumor necroptosis. These results may improve our understanding of NRGs in BRCA and provide a reference for developing individualized therapeutic strategies.

[Percutaneous hollow screw internal fixation combined with cementoplasty in treatment of periacetabular metastasis].

Objective: To explore the percutaneous hollow screw internal fixation combined with cementoplasty in the treatment of periacetabular metastasis. Methods: A retrospective study was performed on 16 patients with periacetabular metastasis who were treated with percutaneous hollow screw internal fixation combined with cementoplasty between May 2020 and May 2021. There were 9 males and 7 females. The age ranged from 40 to 73 years, with an average of 53.6 years. The tumor involved around the acetabulum, and 6 cases were located on the left and 10 cases on the right. Operation time, frequency of fluoroscopy, bed rest time, and complications were recorded. Before operation, and at 1 weeks, 3 months after operation, the visual analogue scale (VAS) score was used to evaluate the pain degree, the short-form 36 health survey scale (SF-36) score was used to evaluate the quality of life. At 3 months after operation, the Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate the functional recovery of patients. During follow-up, the loosening of internal fixator and bone cement leakage were observed by X-ray film. Results: All patients were performed operation successfully. The operation time ranged from 57 to 82 minutes, with an average of 70.4 minutes. The frequency of intraoperative fluoroscopy was 16-34 times, with an average of 23.1 times. After operation, 1 case of incision hematoma and 1 case of scrotal edema occurred. All patients felt the pain relieved after operation. The patients started walking at 1-3 days after operation, with an average of 1.4 days. All patients were followed up 6-12 months (mean 9.7 months). The VAS and SF-36 scores significantly improved after operation when compared with the preoperative scores, and the scores at 3 months after operation were significant better than those at 1 week after operation ( P<0.05). At 3 months after operation, the MSTS score ranged from 9 to 27, with an average of 19.8. Among them, 3 cases were excellent (18.75%), 8 cases were good (50%), 3 cases were fair (18.75%), and 2 cases were poor (12.5%). The excellent and good rate was 68.75%. And 11 patients returned to normal walking, 3 had mild claudication, and 2 had obvious claudication. Radiological examination showed that there were 2 cases of bone cement leakage after operation, and there was no internal fixator loosening or displacement. Conclusion: Percutaneous hollow screw internal fixation combined with cementoplasty can effectively relieve pain and improve the quality of life of patients with periacetabular metastasis.

Three-dimensional High-definition Exoscope in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Retrospective Cohort Study.

OBJECTIVES: The operative microscope (OM) has revolutionized the field of modern spine surgery, however, it remains limited by several drawbacks. Recently, the exoscope (EX) system has been designed to assistant spine surgery. It provides a three-dimensional (3D) high-definition (HD) operative experience and becomes an alternative to the OM. The aim of the study was to evaluate the clinical outcomes, advantages and limitations of EX-assisted minimally invasive transforaminal lumbar interbody fusion (EMIS-TLIF) and OM-assisted MIS-TLIF (OMIS-TLIF). METHODS: The clinical outcomes were assessed in 47 patients with lumbar degenerative diseases (LDD) who underwent MIS-TLIF assisted with the OM or EX between January 2019 and September 2020. A total of 22 were treated with EMIS-TLIF, and 25 received OMIS-TLIF. Perioperative parameters (including sex, age, number of fusion levels and body mass index), perioperative parameters (operation time, intraoperative blood loss, postoperative drainage, postoperative hospitalization stay, and duration of follow-up), visual analogue scale (VAS) of back pain, VAS of leg pain, Oswestry disability index (ODI) scores and clinical outcomes were assessed and compared. Image quality, handling of equipment, ergonomics, 3D glasses and educational usefulness were scored according to a questionnaire. RESULTS: Operation time in the OMIS-TLIF group (121.92 ± 16.92 min) was significantly increased compared with that in the EMIS-TLIF group (111.00 ± 19.87 min) (P < 0.05). The VAS of the back pain and ODI scores in the EMIS-TLIF group were significantly lower compared with the OMIS-TLIF group at 1 week postoperatively (P < 0.05). The good-excellent outcomes rate was 90.91% in the EMIS-TLIF group and 88.00% in the OMIS-TLIF group, and there was no significant difference. A total of 44 visits completed the questionnaire. The results of the questionnaire showed that the EX has exhibited advantages regarding handing of equipment, ergonomics and educational usefulness, and comparable image quality as compared with the OM, however, operating surgeons complained uncomfortable sensation when wearing 3D glasses. CONCLUSIONS: The EMIS-TLIF was a safe and effective procedure in the management of LDD as compared with the OMIS-LIF. Meanwhile, EMIS-TLIF might resulted in a short operation time.

Efficiently targeted therapy of glioblastoma xenograft via multifunctional biomimetic nanodrugs.

BACKGROUND: Glioblastoma multiforme (GBM) is a fatal malignant primary brain tumor in adults. The therapeutic efficacy of chemotherapeutic drugs is limited due to the blood-brain barrier (BBB), poor drug targeting, and short biological half-lives. Multifunctional biomimetic nanodrugs have great potential to overcome these limitations of chemotherapeutic drugs. METHODS: We synthesized and characterized a biomimetic nanodrug CMS/PEG-DOX-M. The CMS/PEG-DOX-M effectively and rapidly released DOX in U87 MG cells. Cell proliferation and apoptosis assays were examined by the MTT and TUNEL assays. The penetration of nanodrugs through the BBB and anti-tumor efficacy were investigated in the orthotopic glioblastoma xenograft models. RESULTS: We showed that CMS/PEG-DOX-M inhibited cell proliferation of U87 MG cells and effectively induced cell apoptosis of U87 MG cells. Intracranial antitumor experiments showed that free DOX hardly penetrated the BBB, but CMS/PEG-DOX-M effectively reached the orthotopic intracranial tumor through the BBB and significantly inhibited tumor growth. Immunofluorescence staining of orthotopic tumor tissue sections confirmed that nanodrugs promoted apoptosis of tumor cells. This study developed a multimodal nanodrug treatment system with the enhanced abilities of tumor-targeting, BBB penetration, and cancer-specific accumulation of chemotherapeutic drugs by combining chemotherapy and photothermal therapy. It can be used as a flexible and effective GBM treatment system and it may also be used for the treatment of other central nervous systems (CNS) tumors and extracranial tumors.

2D Copper(II) Metalated Metal-Organic Framework Nanocomplexes for Dual-enhanced Photodynamic Therapy and Amplified Antitumor Immunity.

The immunosuppressive tumor microenvironment (TME) poses tremendous challenges for efficient immunotherapy. Smart nanomedicine is designed to modulate immunosuppressive TMEs based on the combination of dual-enhanced photodynamic therapy (PDT) triggered immunogenic cell death (ICD) and relieved hypoxic microenvironment. Copper(II) metalated metal-organic framework nanosheets (Cu-TCPP(Al)) are the foundation of the nanomedicine, and platinum nanoparticles (Pt NPs) and folate are subsequently introduced onto the Cu-TCPP(Al) surface (Cu-TCPP(Al)-Pt-FA). Upon targeted cellular uptake, intracellular GSH concentration is decreased because of the specific adsorption between GSH and CuII; meanwhile, Pt NPs possess catalase-like activity, which can continuously depose intracellular H2O2 to O2 to alleviate the hypoxic TME. The two factors synergistically improve the ROS concentration for dual-enhanced PDT. The highly toxic ROS can correspondingly cause amplified oxidative stress and then trigger the ICD. The ICD process stimulates antigen-presenting cells and activates the systemic antitumor immune response. Furthermore, the relieved hypoxic TME increases the infiltration of cytotoxic T lymphocytes (CTLs) at the tumor site, which can promote the transformation of the immunosuppressive M2 macrophage to immunoactive M1 phenotype. The easily prepared yet versatile nanomedicine possesses an excellent antitumor effect with the cooperation of dual-enhanced PDT and immunotherapy.

TfR Aptamer Enhanced Blood-Brain Barrier Penetration of Biomimetic Nanocomplexes for Intracellular Transglutaminase 2 Imaging and Silencing in Glioma.

Engineering a versatile nanocomplex integrating effective penetration of the blood-brain barrier (BBB), accurate diagnosis, and boosting therapy has always been an intractable challenge in glioblastoma multiforme (GBM). Herein, biomimetic nanocomplexes (TMPsM) for single intracellular transglutaminase 2 (TG2)-triggered self-assembly imaging and RNAi therapy for GBM are subtly developed. To prove the concept, transferrin receptor (TfR) aptamer-modified brain metastatic tumor cell membrane is prepared as the shell for dual BBB targeting capability and prolonged blood retention time. Upon targeting entering into GBM, hollow MnO2 is decomposed to release KKGKGQQ-tetraphenylethene (Pep-TPE) and siRNA. Owing to TG2 dependence, the non-emissive Pep-TPE would be self-aggregated to induce the emission turn-on in GBM that contain overexpressed TG2. The resulting aggregation-induced emission fluorescence imaging with a high signal-to-noise ratio can achieve the precise localization of the tumor and dynamic detection of TG2 activity, thereby allowing the GBM accurate diagnosis. Notably, the TG2 can be silenced by the released siRNA to cause cell apoptosis and increase chemotherapeutic sensitivity, ultimately realizing excellent antitumor efficacy. In vitro and in vivo results demonstrate that the as-prepared TMPsM indeed possess superior BBB penetration, precise diagnosis, and effective therapy of GBM. The proposed strategy may pioneer a new path for the theranostics of brain tumors.

Can prophylactic negative pressure wound therapy improve clinical outcomes in spinal fusion surgery? A meta-analysis.

PURPOSE: Recently negative pressure wound therapy (NPWT) is increasingly being prophylactically used to prevent wound complications in various types of surgeries, but its role in spinal fusion surgery was less well established. This study aimed to evaluate the efficacy of prophylactic NPWT (PNPWT) usage in spinal fusion surgery. METHODS: Following PRISMA guidelines, databases PubMed, Embase and Web of Science were searched for relevant studies. Studies comparing PNPWT with standard wound dressing (SWD) were included and analyzed. The primary outcome was the incidence of surgical site infection, and secondary outcomes were incidence of wound dehiscence, overall wound complication, readmission and reoperation. RESULTS: A total of five studies were included; there were 279 patients in PNPWT group and 715 patients in SWD group. Four studies investigated surgical site infection; the pooled analysis showed a significantly lower incidence of surgical site infection in PNPWT group (OR: 0.399; 95% CI: 0.198, 0.802). Two studies explored wound dehiscence, three studies reported overall wound complication, and there were no significant differences between the two groups ((OR: 0.448; 95% CI: 0.144, 1.389) and (OR: 0.562; 95% CI: 0.296, 1.065), respectively). Two studies evaluated readmission, three studies compared reoperation rate, and the pooled results demonstrated no significant difference between the two groups ((OR: 1.045; 95% CI: 0.536, 2.038) and (OR: 0.979; 95% CI: 0.442, 2.169), respectively). CONCLUSIONS: The current evidence suggested PNPWT could effectively reduce postoperative surgical site infection, but it had no significant benefit on reducing the incidence of wound dehiscence, overall wound complication, readmission and reoperation.

A real-time 3D electromagnetic navigation system for percutaneous transforaminal endoscopic discectomy in patients with lumbar disc herniation: a retrospective study.

BACKGROUND: In this study, we present a novel electromagnetic navigation (EMN) system for percutaneous transforaminal endoscopic discectomy (PTED) procedure. The objective of this study was to investigate the safety and effectiveness of the PTED with the assistance of the EMN system and compare it with the conventional PTED with the assistance of fluoroscopic guidance (C-arm). METHODS: The clinical data of 79 patients (32 in EMN group and 47 in C-arm group) undergoing PTED for lumbar disc herniation (LDH) from January to September of 2019 were analyzed retrospectively. The radiation time, puncture time, operation time, visual analog scale (VAS), Oswestry disability index (ODI), modified MacNab criteria, and radiological parameters were recorded in both groups. RESULTS: Radiation time, puncture time, and operation time were significantly reduced in the EMN group compared with the C-arm group (P < 0.05). Compared with the C-arm group, a steeper learning curve was observed in the EMN group. There were no significant differences between the two groups regarding VAS and ODI scores at different time points (P > 0.05). The satisfaction rates of the EMN and C-arm groups were 90.63 and 87.23%, respectively, but no significant difference was found between the two groups (P > 0.05). There was no significant difference regarding translation and angular motion between the two groups at preoperation and postoperation (P > 0.05). CONCLUSIONS: The EMN system can be applied to facilitate the PETD procedure. It can significantly reduce the intraoperative radiation time, puncture time, and operation time, and reshape the learning curve of PTED. Due to limitations of a retrospective study, results may need validation with larger prospective randomized clinical trials.

A real-time 3D electromagnetic navigation system for percutaneous pedicle screw fixation in traumatic thoraco-lumbar fractures: implications for efficiency, fluoroscopic time, and accuracy compared with those of conventional fluoroscopic guidance.

PURPOSE: Navigation is becoming more useful in percutaneous pedicle screw fixation (PPSF). The aim of this study was to compare the efficiency, fluoroscopic time, accuracy, and clinical outcomes of PPSF with a novel electromagnetic navigation (EMN) system for thoraco-lumbar (TL) fractures with those of PPSF with conventional C-arm fluoroscopic (CF) guidance. METHODS: A retrospective study was conducted. A total of 162 screws were implanted in 29 patients with the assistance of the EMN system (EMN group), and 220 screws were inserted in 40 patients by using CF guidance (CF group). The duration of surgery, placement time per screw, fluoroscopic time per screw, accuracy of pedicle screw placement, and clinical outcomes were compared between the two groups. RESULTS: The duration of surgery and placement time per screw in the EMN group were significantly lower than those in the CF group (P < 0.05). The fluoroscopic time per screw in the CF group was significantly longer than that in the EMN group (P < 0.05). The learning curve of PPSF in the EMN group was steeper than that in the CF group. The accuracy of pedicle screw placement in the EMN group was more precise than that in the CF group (P < 0.05). The VAS scores in the EMN group were significantly lower than those in the CF group at one-week postoperatively (P < 0.05). CONCLUSION: Compared with PPSF by using conventional fluoroscopic guidance, PPSF with the aid of the EMN system can increase the efficiency and accuracy of pedicle screw placement and reduce the fluoroscopic time.

Three-dimensional high-definition exoscope (Kestrel View II) in anterior cervical discectomy and fusion: a valid alternative to operative microscope-assisted surgery.

BACKGROUND: Operative microscope (OM) has greatly advanced modern spine surgery, but remains limited by several drawbacks. Therefore, a three-dimensional (3D) high-definition (HD) exoscope (EX) (Kestrel View II, Mataka Kohli, Japan) system has been developed and used as an alternative to the OM. The aim of this study was to assess and compare the perioperative data and clinical outcomes of anterior cervical discectomy and fusion (ACDF) procedure with either an EX or OM. METHODS: Forty-eight patients with cervical spondylotic myelopathy (CSM) underwent ACDF assisted by the EX or OM between January 2019 and December 2019. We collected and compared data on operative time, intraoperative bleeding, postoperative hospitalization stay, complications, and clinical outcomes between the two groups. The clinical outcomes were evaluated by using visual analogue scale (VAS) scores, Japanese Orthopedic Association (JOA) scores, the recovery rate of JOA scores, and Odom criteria. RESULTS: The operative time in the EX group was significantly shorter than that in the OM group (P < 0.05). The VAS and JOA scores were significantly improved in both groups after surgery (P < 0.05). In addition, the VAS scores in the EX group were significantly lower than those in the OM group at 1 week postoperatively (P < 0.05). The good-to-excellent outcome rates were 90.48 and 88.89% in the EX group and OM group, respectively, whereas the complication occurrence rates of the EX group and OM group were 4.76 and 11.11%, respectively. CONCLUSIONS: EX-assisted and OM-assisted ACDF resulted in similar clinical outcomes for CSM, while EX-assisted surgery may be related to a short operative time and fewer complications.

Clinical outcomes of transforaminal endoscopic lateral recess decompression by using the visualized drilled foraminoplasty and visualized reamed foraminoplasty: a comparison study.

BACKGROUND: Lateral recess stenosis (LRS) is a common degenerative disease in the elderly. Since the rise of comorbidity is associated with increasing age, transforaminal endoscopic lateral recess decompression (TE-LRD) is advocated. The objective of this study was to compare the clinical outcomes of TE-LRD in patients with LRS via visualized drilled foraminoplasty (VDF) or visualized reamed foraminoplasty (VRF) technique. METHODS: A total of 45 and 42 consecutive patients with limp or unilateral radiculopathy symptoms underwent TE-LRD using the VDF and VRF technique, respectively. The radiation exposure and operation time, time to return to work, and complications were compared between two groups. Their clinical outcomes were evaluated with the visual analogue scale (VAS) leg pain score, VAS back pain score, Oswestry Disability Index (ODI) and modified MacNab's criteria. RESULTS: The average values of radiation exposure and operative time in the VDF group were significantly higher than those in the VRF group (P <  0.05). The postoperative VAS and ODI scores in both groups were significantly improved compared with those before the operation (P <  0.05). In addition, the VAS score of the leg pain and ODI score in the VRF group were significantly lower than those in the VDF group at the 1-week follow-up (P <  0.05). The good-to-excellent rates of the VDF group and VRF group were 88.89 and 90.48%, respectively, whereas the complication occurrence rates were 6.67 and 4.76% in the VDF group and VRF group, respectively. CONCLUSIONS: TE-LRD performed by using VRF technique can be applied to treat LRS safely and effectively with short radiation exposure and operation time. This technique was comparable to the VDF technique with improved VAS leg pain and ODI scores in the short period after the operation. However, potential complications and risks still need to be considered.

Metal artifact reduction using mono-energy images combined with metal artifact reduction software in spectral computed tomography: a study on phantoms.

BACKGROUND: This study aimed to evaluate the effectiveness of spectral computed tomography (CT) mono-energy imaging combined with metal artifact reduction software (MARs) for metal implant artifact reduction using a phantom. METHODS: A quantitative standard phantom with 9 cylinders was used to simulate the attenuation of the different tissues of the human body around the metal implant. Groups A and B were divided according to conventional CT scan mode and spectral CT scan mode. Three sets of reconstructed images, including 120 kVp-like + MARs images, mono-energy images (MonoE), and MonoE + MARs images, were generated after spectral CT scanning. High-attenuation artifacts and low-attenuation artifacts were observed around the coil in the images of groups A and B. The CT values (Hounsfield unit) and standard deviation (SD) values of the artifacts were measured, and the artifact index and hardening artifact removal rate were calculated. RESULTS: Compared to conventional poly-energy CT images, for high-attenuation and low-attenuation artifacts, the artifact indices of 120 kVp-like + MARs, MonoE, and MonoE + MARs images were all reduced significantly. The hardening artifact removal rates of the high-attenuation and low-attenuation artifacts of 120 kVp-like + MARs images were 82% and 92%, respectively. The hardening artifact removal rate of the high-attenuation and low-attenuation artifacts of MonoE and MonoE + MARs images increased with the mono-energy level. CONCLUSIONS: Spectral CT using the 120 kVp-like + MARs, 110-140 keV MonoE, and MonoE + MARs reconstruction methods can reduce metal implant artifacts in varying degrees. MonoE + MARs reconstruction was the best method for reducing metal artifacts.