The learning curve for minimally invasive Achilles repair using the "lumbar puncture needle and oval forceps" technique.

INTRODUCTION: An acute Achilles tendon rupture represents a common tendon injury, and its operative methods have been developed over the years. This study aimed to quantify the learning curve for the minimally invasive acute Achilles tendon rupture repair. METHODS: From May 2020 to June 2022, sixty-seven patient cases who received minimally invasive tendon repair were reviewed. Baseline data and operative details were collected. The cumulative summation (CUSUM) control chart was used for the learning curve analyses. Achilles tendon rupture score (ATRS), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, and visual analog scale (VAS) at 3/6/9/12 months were calculated to assess the clinical outcomes. RESULTS: Thirty-six cases underwent at least a year of follow up and were enrolled in this study. The gender ratio and average age were 80.5% and 32.5 years. The linear equation fitted well (R2 = 0.95), and CUSUM for operative time peaked in the 12th case, which was divided into the learning phase (n = 12) and master phase (n = 24). No significant difference was detected between the two groups in clinical variables, except for the operative time (71.1 ± 13.2 min vs 45.8 ± 7.2 min, p = 0.004). Moreover, we detected one case with a suture reaction and treated it properly. CONCLUSION: Minimally invasive Achilles repair provides an opportunity for early rehabilitation. Notably, the learning curve showed that the "lumbar puncture needle and oval forceps" technique was accessible to surgeons.

Formaldehyde-free and durable phosphorus-containing cotton flame retardant with -N=P-(N)3- and reactive ammonium phosphoric acid groups.

A flame retardant (FR) hexachlorocyclotriphosphazene diethylenetriamine ammonium phosphoric acid (HDAPA) was synthesized. Vertical flammability test and limiting oxygen index (LOI) results showed that cotton samples finished with HDAPA solutions (15 % and 20 %) could pass vertical flame retardancy test, and LOIs reached 30.1 % and 35.4 % even after 50 laundering cycles according to AATCC 61-2013 3A washing standard (3A), performing flame retardancy and washing durability. Meanwhile, Fourier transform infrared and X-ray photoelectron spectroscopy analyses suggested that HDAPA was grafted on cotton fibers through -P(=O)-O-C covalent bond. Total heat release (1.98 MJ/m2) and char residue (16.2 %) of HDAPA treated cotton were much lower than those (4.26 MJ/m2, 3.2 %) of untreated cotton. Thermogravimetry results showed HDAPA changed thermal decomposition pathway of cotton fabric, which was further supported by thermogravimetric-Fourier infrared spectrometer results, revealing HDAPA performed a condensed phase flame retardancy mechanism. Scanning electron microscopy implied HDAPA entered amorphous region of cotton fibers to react with cellulose. Mechanical properties of HDAPA treated cotton decreased a little. Although the synthesis process used formaldehyde but no free formaldehyde released. In consequence, the aforementioned results indicated that the introduction of -N=P-(N)3- and -P(=O)(O-NH4+)2 groups to FR was an viable method to improve flame retardancy and durability.

A cationic, durable, P/N-containing starch-based flame retardant for cotton fabrics.

A cationic, durable flame retardant for cotton fabrics, 6-(2-(dimethoxy phosphoryl)-2-(trimethyl ammonium)) methoxy-2-methoxy-polysaccharide ammonium phosphate (DTPAP), was synthesized. Its structure was verified by NMR and FTIR spectroscopy. According to the FTIR spectra and X-ray photoelectron spectroscopy (XPS), DTPAP formed P(=O)-O-C bonds with cellulose molecules and firmly grafted to cotton fabrics, giving the fabric a high durability. DTPAP-25-treated fabrics passed the vertical flame test (VFT), and the limiting oxygen index (LOI) was 43.9 %. After 50 laundering cycles (LCs), the DTPAP-25-treated fabrics had an LOI of 29.9 %, passed the VFT, and retained their flame retardancy. EDS data showed that, compared with engrafted cationic ammonium phosphate flame retardants, the DTPAP-treated fabrics contained fewer metal ions. Cone calorimetry data showed that DTPAP-25-treated fabrics did not display concentrated heat release. The results suggested that DTPAP exhibited a condensed-phase flame retardant mechanism, and the introduction of cations into the ammonium phosphate flame retardant reduced ion exchange, which improved the durability.

A new method regulates bone fracture tissue exosome lncRNA-mRNA to promote mesenchymal stem cell proliferation and migration.

Post-injury adaptation (PIA) is a simple and convenient method to promote bone healing, but its mechanism is unclear. This study was to discuss the role of fracture site tissue exosomes lncRNAs-mRNAs networks on PIA promoting bone mesenchymal stem cells (BMSCs) proliferation and migration. Firstly, the effects of PIA accelerating BMSCs proliferation and migration were confirmed by rat fracture model and bone fracture environment in vitro. Besides, the fracture site tissue exosomes were isolated and authenticated. Then the tissue exosomes were the key factor in PIA promoting BMSCs proliferation and migration authenticated by in vitro and in vivo experiments. The high throughput sequencing and RT-PCR were used to analyze the tissue exosomes lncRNAs-mRNAs networks. It was found that PIA treatment upregulated 118 lncRNAs, 295 mRNAs, and downregulated 111 lncRNAs, 2706 mRNAs in tissue exosomes. A total 12,211 genes were the target genes. Akt1, Actb and Uba52 were the hub mRNAs in tissue exosomes. In additions, tissue-derived exosomes of PIA treated rats upregulated 49 genes, 3 lncRNAs and downregulated 28 genes, 1 lncRNA in BMSCs. Kif11 was the hub gene. Overall, PIA promoted BMSCs proliferation and migration in the early stage of fracture healing, which was closely related to the fracture site tissue exosomes. Akt1, Actb and Uba52 were the hub mRNAs in the exosomes. Besides, Kif11 might be the key gene in BMSC regulated by tissue-derived exosomes of PIA treated rats.

Efficiency evaluation and nonlinear multi-objective optimization of forestry industry transformation in the Heilongjiang state-owned forest region.

With the deepening of the concept of sustainable development of the whole society, protecting forest resources has become a crucial task of the current society. The present forestry industrial structure of Heilongjiang state-owned forest areas has undergone significant changes, and the transformation of the forestry industry has become increasingly prominent. How to deepen the forestry industry transformation and improve its efficiency has become an important research direction in forest areas. This work first analyzes the data envelopment method, and further designs the evaluation method of forestry transformation efficiency in forest areas. Then, the evaluation index system of forestry industry transformation efficiency in Heilongjiang state-owned forest areas is built. The relevant nonlinear multi-objective optimization (MOO) constraints are designed. Relevant data are quoted to evaluate the efficiency of the forestry industry transformation in the Heilongjiang state-owned forest areas. The results show that: (1) During 2015-2021, the average value of the scale, technical, and comprehensive production efficiencies of Heilongjiang state-owned forest areas were 0.765, 0.53, and 0.399, all of which were less than 1. And they were in a relatively ineffective state. (2) The overall industrial transformation of state-owned forest areas was optimistic. The technical efficiency decreased slightly in 2017, while the pure technical efficiency was greater than 1 in 2016 and 2018. The efficiency value increased to the peak by the end of 2021. (3) In the transformation of the forestry industry in state-owned forest areas, the influence of the industrial economy and resource protection subsystems was the first and backward, and the contribution of the social development subsystem was in the middle. (4) In the MOO problem, the forest area should be planned according to the proportion of public welfare, multi-functional, and commercial forests: 35.2%, 38.8%, and 26%, respectively. This work provides an essential reference for protecting forest resources and contributes to the transformation and development of the social forestry industry.

Comparative Analysis of Eccentric Glenosphere in Reverse Total Shoulder Arthroplasty: A Computer Simulation Study.

Objective: The aim was to evaluate the effects of different glenosphere eccentricities on impingement, range of motion (ROM), and muscle length during standard activities in reverse total shoulder arthroplasty (RSA). Methods: In this study, we utilized computational modeling techniques to create native shoulder and shoulder models undergoing RSA and simulate shoulder movements in all abduction-adduction, flexion-extension, and rotation. We tested a total of 36 different glenosphere configurations, which included three different inferior tilts (0°, +10°, +20°) and two different lateral offsets (0 mm and +4 mm), as well as six different glenosphere eccentricities (concentricity, inferior, posterior, anterior, anteroinferior, and posteroinferior). We evaluated the maximum impingement-free ROM, impingement sites, and muscle lengths. Results: All glenosphere configurations exceeded 50% of native shoulder ROM in three planes and total global ROM. In abduction-adduction, there was no significant difference among the different glenosphere eccentricities (p > 0.05). In flexion-extension, the posteroinferior eccentricity had the maximum ROM among the different eccentricities, but no significant difference among the different glenosphere eccentricities (p > 0.05). In rotation, there was a significant difference overall, and anteroinferior eccentricity had a significant advantage over concentricity (p < 0.05). In total global ROM, anteroinferior eccentricity had a significant advantage over concentricity when lateral offset was 0 mm (p < 0.05). In all models of glenosphere eccentricities, only the elongation of the infraspinatus muscle was statistically significant (p < 0.05). Conclusion: Glenosphere eccentricity significantly influenced rotation, total global ROM, and the length of the subscapularis muscle. Among them, anteroinferior offset achieved the maximum ROM in abduction-adduction, rotation, and total global activities. Both anteroinferior and inferior glenoid eccentricity showed significant advantages over the concentricity in rotation and total global ROM. Level of Evidence: Basic Science Study; Computer Modeling.

The Role of Combined Inflammatory Biomarkers in the Diagnosis of High- and Low-Virulence FRI Among High-Risk Lower Extremity Fractures.

Objective: The aim of this study is to evaluate the diagnostic accuracy of infection-related biomarkers in high-risk lower limb injury patients with fracture-related infection (FRI) caused by high-/low-virulence microorganisms. Methods: This study was a retrospective analysis of patients with high-risk lower extremity fractures (including tibial plateau, calcaneus, and Pilon fractures) who underwent open reduction internal fixation (ORIF) surgery from January 2017 to February 2022. Peripheral blood samples were collected within 24 hours of admission, and the following information was evaluated: gender, age, BMI, smoking, comorbidities, injury information, surgical details, values for serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), as well as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR). Results: A total of 576 patients receiving lower extremity fracture surgery were included in this study. Fifty-one patients (8.85%) were identified as FRI, and 28 (54.9%) of these 51 cases were further classified as high-virulence group. The median levels of CRP, ESR, NLR, and MLR were significantly higher in the FRI group than in the non-FRI group (p < 0.01). Similarly, the marginally significantly higher levels of CRP and NLR presented in the high-virulence group, compared to the low-virulence group (p < 0.1). The AUC areas of CRP, NLR, and CRP+NLR were 0.826, 0.650, and 0.873, respectively. We calculated the optimal cut-off points for CRP+NLR as diagnostic markers of high-virulent infection was 0.377. Conclusion: This study showed the incidence of FRI in high-risk lower extremity fractures was 8.9%, and identified preoperative serum biomarkers, including CRP, ESR, NLR, and PLR, as useful tools for assisting in the diagnosis of infection. Additionally, the combination of CRP with NLR played a discriminating clinical role in postoperative infections caused by different virulence. Level of Evidence: Clinical study.

Long Non-Coding RNAs Within Macrophage-Derived Exosomes Promote BMSC Osteogenesis in a Bone Fracture Rat Model.

Purpose: To investigate the effect of macrophage exosomal long non-coding (lnc)RNAs on bone mesenchymal stem cell (BMSC) osteogenesis and the associated mechanism. Methods: Rat BMSCs and spleen macrophages were co-cultured with serum derived from the fracture microenvironment of rat tibia. BMSC osteogenesis was evaluated using Alizarin red staining and the expression of BMP-2, RUNX2, OPN, and OC mRNA. BMSC osteogenesis was evaluated after co-culture with macrophages stimulated using hypoxic conditions or colony-stimulating factor (CSF). The uptake of macrophage-derived exosomes by BMSCs was evaluated using the exosome uptake assay. High-throughput sequencing and bioinformatics analyses were performed to identify key lncRNAs in the macrophage exosomes. The effect of lncRNA expression levels on BMSC osteogenesis was also assessed using a lncRNA overexpression plasmid and siRNA technology. M1 and M2 macrophages were distinguished using flow cytometry and the key exosomal lncRNA was detected by in situ hybridization. Results: In the fracture microenvironment, macrophages (stimulated using either hypoxia or CSF) significantly increased the osteogenic ability of BMSCs. We showed that BMSCs assimilated macrophage-derived vesicles and that the inhibition of exosomal secretion significantly attenuated the macrophage-mediated induction of BMSC osteogenesis. The hypoxia condition led to the up-regulation of 310 lncRNAs and the down-regulation of 575 lncRNAs in macrophage exosomes, while CSF stimulation caused the up-regulation of 557 lncRNAs and the down-regulation of 407 lncRNAs. In total, 108 lncRNAs were co-up-regulated and 326 lncRNAs were co-down-regulated under both conditions. We eventually identified LOC103691165 as a key lncRNA that promoted BMSC osteogenesis and was expressed at similar levels in both M1 and M2 macrophages. Conclusion: In the fracture microenvironment, M1 and M2 macrophages promoted BMSC osteogenesis by secreting exosomes containing LOC103691165.

Intrawound application of vancomycin reduces the proportion of fracture-related infections in high-risk tibial plateau fractures.

INTRODUCTION: Despite the improvements in surgical techniques and the use of prophylactic intravenous antibiotics, the fracture-related infection (FRI) incidence after high-risk tibial plateau fractures remains high. This study aimed to evaluate the clinical effect of the intrawound application of vancomycin on the FRI after high-risk tibial plateau fracture surgery. METHODS: A total of 243 patients who underwent high-risk tibial plateau fracture surgery from May 2013 to June 2021 were retrospectively reviewed. Of these, 233 cases were enrolled. Considering the preoperative patient condition, surgeons applied vancomycin powder directly into the surgical site before wound closure in 105 cases (intrawound application of vancomycin powder with preoperative intravenous cephalosporin). The remaining 128 cases served as the control group (preoperative intravenous cephalosporin alone). Clinical data and surgical details were recorded. The Cox proportional hazards regression analysis was used to assess risk factors for FRI. The Kaplan-Meier method and the log rank test illustrated the infection status of patients based on the application of intrawound vancomycin. The primary outcome was an FRI within one year. Secondary outcomes included bacterial culture and vancomycin-related complications. RESULTS: Our study demonstrated a significant difference in the incidence of FRI between the vancomycin group and the control group (3.8% versus 10.9%; p=0.041). Multivariable Cox regression showed the intrawound application of vancomycin powder decreased the rate of FRI. There were no complications related to intrawound vancomycin observed during follow-up. The presence of Gram-positive FRI was higher in the control group compared with the vancomycin group. CONCLUSIONS: Intrawound application of vancomycin was associated with a significant lower rate of FRI after high-risk tibial plateau fracture surgery compared to the control group.

Pharmacokinetic/Pharmacodynamic Evaluation of Aztreonam/Amoxicillin/Clavulanate Combination against New Delhi Metallo-ß-Lactamase and Serine-ß-Lactamase Co-Producing Escherichia coli and Klebsiella pneumoniae.

This study aimed to examine specific niches and usage for the aztreonam/amoxicillin/clavulanate combination and to use population pharmacokinetic simulations of clinical dosing regimens to predict the impact of this combination on restricting mutant selection. The in vitro susceptibility of 19 New-Delhi metallo-ß-lactamase (NDM)-producing clinical isolates to amoxicillin/clavulanate and aztreonam alone and in co-administration was determined based on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). The fractions of a 24-h duration that the free drug concentration was within the mutant selection window (fTMSW) and above the MPC (fT>MPC) in both plasma and epithelial lining fluid were determined from simulations of 10,000 subject profiles based on regimens by renal function categories. This combination reduced the MIC of aztreonam and amoxicillin/clavulanate to values below their clinical breakpoint in 7/9 K. pneumoniae and 8/9 E. coli, depending on the ß-lactamase genes detected in the isolate. In the majority of the tested isolates, the combination resulted in fT>MPC > 90% and fTMSW < 10% for both aztreonam and amoxicillin/clavulanate. Clinical dosing regimens of aztreonam and amoxicillin/clavulanate were sufficient to provide mutant restriction coverage for MPC and MIC ≤ 4 mg/L. This combination has limited coverage against NDM- and extended-spectrum ß-lactamase co-producing E. coli and K. pneumoniae and is not effective against isolates carrying plasmid-mediated AmpC and KPC-2. This study offers a potential scope and limitations as to where the aztreonam/amoxicillin/clavulanate combination may succeed or fail.

The combination effect of meropenem/sulbactam/polymyxin-B on the pharmacodynamic parameters for mutant selection windows against carbapenem-resistant Acinetobacter baumannii.

The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against Acinetobacter baumannii harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B. Combining meropenem and polymyxin-B with or without sulbactam resulted in synergistic bactericidal activities. Pharmacokinetic (PK) simulations of drug concentrations in the blood and epithelial lining fluid coupled with pharmacodynamic (PD) evaluations revealed that the fractions of time over the 24-h in terms of free drug concentration within the MSW (fTMSW) and above the MPC (fT>MPC) were optimized by combination therapy. The resultant clinical regimens of meropenem, polymyxin-B, and sulbactam evaluated in the PK-PD analysis were 2 g q8h, 2.5 mg/kg loading dose followed by 1.5 mg/kg q12h, and 3 g q8h, respectively, in patients with normal renal function. Subsequent corresponding equivalent exposure regimens would depend on the extent of renal failure. The overall results indicate that combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can confer potential efficacy against A. baumannii harboring OXA-23, and reduce the opportunity for bacteria to develop further resistance. This study provides a framework for pharmacodynamic evaluation of drug-resistant mutant suppression in an antimicrobial co-administration setting. The results thereby lay the groundwork for additional studies and future clinical confirmation is warranted.

Bone homeostasis disorders increased the mortality of sepsis patients: A preliminary retrospective cohort study.

Introduction: Sepsis is a common clinical syndrome and nearly 20% of all deaths are related to sepsis. As an important part of the body, bone homeostasis disorders are closely related to inflammatory response, but the correlation between bone homeostasis and sepsis, sepsis shock was unknown. The objective of this study was to explore the relation of bone homeostasis on sepsis and sepsis shock. Methods: In this retrospective cohort study, patients were enrolled between April 2018 and May 2022 from Beijing Chaoyang hospital. Primary outcomes were serum indicators reflected bone homeostasis, such as cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I), tartrate-resistant acid phosphatase 5b (TRACP-5b) and piezo-type mechanosensitive ion channel component 1 (PIEZO1). Results: The data were analyzed retrospectively. among 88 evaluable patients, 45 were sepsis (19 were sepsis shock) and 43 were non-sepsis. There was no significant difference in age, gender, BMI, combination diseases, operation time, intraoperative blood loss, and hospital stay. Patients with sepsis or sepsis shock had higher serum CTX-I, TRACP-5b, PIEZO1 (p < 0.05). Spearman's rank correlation test showed that CTX-I, TRACP-5b, PIEZO1 and the three together (CTX-I + TRACP-5b + PIEZO1) had strong correlation with sepsis or sepsis shock (p < 0.05). The receiver operating characteristic curve (ROC) and precision-recall curve (PRC) showed that these indicators could predict the occurrence of sepsis or sepsis shock (p < 0.05). Besides, decision curve analysis (DCA) and interventions avoided curve (IAC) displayed a high net benefit of bone homeostasis disorders indicators on sepsis or sepsis shock. Kaplan-Meier survival curves revealed that sepsis or shock patients with high value indicators (>0.47227) had a higher mortality (p < 0.05). Conclusion: Bone homeostasis disorders could increase the mortality of sepsis and sepsis shock patients.

Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii.

Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant Acinetobacter baumannii at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit in vitro synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of A. baumannii harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) from simulated pharmacokinetic profiles. The combination of these three antibiotics can confer susceptibility in multi-drug resistant A. baumannii and reduce the opportunity for bacteria to develop further resistance. Clinical intravenous dosing regimens of amikacin, polymyxin-B, and sulbactam were predicted to optimize fTMSW and fT>MPC from drug exposures in the blood. Mean fT>MPC were ≥ 60% and ≥ 80% for amikacin and polymyxin-B, whereas mean fTMSW was reduced to <30% and <15%, respectively, in the triple antibiotic combination. Due to the low free drug concentration of amikacin and polymyxin-B simulated in the epithelial lining fluid, the two predicted pharmacodynamic parameters in the lung after intravenous administration were not optimal even in the combination therapy setting.

Risk factors and new inflammatory indicators of deep vein thrombosis after adult patella fractures.

Objective: This study aimed to investigate the association between new inflammatory indicators at admission and the occurrence of preoperative deep vein thrombosis (DVT) in patients with patella fractures. Methods: A retrospective analysis of the medical records of patients aged 18 years or older who underwent surgical treatment for unilateral closed patella fractures at our hospital between August 2016 and August 2020. The incidence of preoperative DVT was detected by Duplex ultrasound (DUS). Partial blood routine and biochemical indexes were collected at admission, and the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) of inflammatory indexes were also calculated. ROC was used to analyze the cut-off value NLR, MLR, and PLR for predicting preoperative DVT, and univariate and multivariate analyses of the risk factors for preoperative DVT of patella fractures, and to verify whether other risk factors affecting the relationship between validation indexes and preoperative DVT. Results: A total of 500 patients were included, of which 39 patients (7.8%) developed preoperative DVT. After univariate and multivariate analysis, preoperative time (in each day delay), male (vs. female), D-dimer > 0.6 mg/L, total cholesterol (TC) > 5.6 mmol/L, and PLR > 189.8 were the risk factors for preoperative DVT in patients with patella fracture. Inflammation index PLR combined with the other four risk factors significantly improved the predictive efficacy of preoperative DVT compared with PLR (P = 0.009). Conclusion: Inflammatory index PLR is a risk factor for preoperative DVT in patients with patella fracture, and the efficacy of PLR in predicting DVT can be significantly improved when other risk factors (male, D-dimer > 0.6 mg/L, TC > 5.6 mmol/L, and PLR > 189.8 of preoperative time in each day delay) are combined. These data are useful for the clinical identification of patients at high risk of preoperative DVT in patella fractures.

Immune cell infiltration and cytokine secretion analysis reveal a non-inflammatory microenvironment of medulloblastoma.

Medulloblastoma (MB) is the most common lethal malignant pediatric brain tumor. Adjuvant immunotherapy for medulloblastoma has been proposed in both pre-clinical and clinical practice. To provide a precision strategy of designing immunotherapy for MB, the present study performed a descriptive analysis of immune microenvironment in a cohort and compared the differences between four subgroups of MB. Subtypes (WNT, SHH Group 3 and Group 4) of medulloblastoma were identified using K-means clustering according to the expression of signature genes. Tumor infiltrating immune cell population was assessed by both bio-informative algorithm based on gene expression and immunohistochemistry staining. Cytokines in tumor microenvironment were detected using Luminex. Gene Set Enrichment Analysis demonstrated a raised immune response in the SHH subgroup. Lymphocyte infiltration was low in all four subgroups, while more CD4+ T cells were observed in the Group 4 subtype. Programmed cell death protein 1 (PD1)/ ligand 1 (PD-L1) expression was absent in the cohort. The SHH subtype recruited more activated tumor associated macrophage/microglia compared with the other subgroups. Cytokines within the MB microenvironment were low compared with the glioblastoma samples. In contrast to glioblastoma, the immune microenvironment of pediatric MB is non-inflammatory and does not recruit many immune cells. These observations provide important considerations for the design of immunotherapeutic approaches for MB, such as inducing more lymphocytes into the tumor microenvironment.

IL-17A promotes cell migration and invasion of glioblastoma cells via activation of PI3K/AKT signalling pathway.

Glioblastomas (GBMs) are the most common of both benign and malignant primary brain tumours, in which the inflammatory and immunologic abnormalities are involved. Interleukin-17A (IL-17A) plays an important role in various inflammatory diseases and cancers. Several recent studies revealed that the expression of IL-17A was overexpressed in human GBMs tissue. However, the accurate role of IL-17A in GBMs remains unclear. In this study, we aimed to explore the effect of IL-17A on cell migration and invasion of GBMs and the mechanism by which the effects occurred. We found that exogenous IL-17A promoted significantly cell migration and invasion abilities in two GBMs cell lines (U87MG and U251) in a time-dependent manner. In addition, the protein expressions of PI3K, Akt and MMP-2/9 were increased in the GBMs cells challenged by IL-17A. Furthermore, a tight junction protein ZO-1 was down-regulated but Twist and Bmi1 were up-regulated. Treatment with a PI3K inhibitor (LY294002) significantly reduced the abilities of both migration and invasion in U87MG and U251 cells. LY294002 treatment also attenuated the IL-17A causing increases of protein levels of PI3K, AKT, MMP-2/9, Twist and the decreases of protein level of ZO-1 in the U87MG and U251 cells. Taken together, we concluded that IL-17A promotes the GBM cells migration and invasion via PI3K/AKT signalling pathway. IL-17A and its related signalling pathways may be potential therapeutic targets for GBM.

3D NIR-II Molecular Imaging Distinguishes Targeted Organs with High-Performance NIR-II Bioconjugates.

Greatly reduced scattering in the second near-infrared (NIR-II) region (1000-1700 nm) opens up many new exciting avenues of bioimaging research, yet NIR-II fluorescence imaging is mostly implemented by using nontargeted fluorophores or wide-field imaging setups, limiting the signal-to-background ratio and imaging penetration depth due to poor specific binding and out-of-focus signals. A newly developed high-performance NIR-II bioconjugate enables targeted imaging of a specific organ in the living body with high quality. Combined with a home-built NIR-II confocal set-up, the enhanced imaging technique allows 900 µm-deep 3D organ imaging without tissue clearing techniques. Bioconjugation of two hormones to nonoverlapping NIR-II fluorophores facilitates two-color imaging of different receptors, demonstrating unprecedented multicolor live molecular imaging across the NIR-II window. This deep tissue imaging of specific receptors in live animals allows development of noninvasive molecular imaging of multifarious models of normal and neoplastic organs in vivo, beyond the traditional visible to NIR-I range. The developed NIR-II fluorescence microscopy will become a powerful imaging technique for deep tissue imaging without any physical sectioning or clearing treatment of the tissue.

Trefoil factor 3 contributes to the malignancy of glioma via regulating HIF-1α.

Trefoil factor 3 (TFF3) plays significant roles in several solid tumors. However, the expression pattern and function of TFF3 in glioblastoma (GBM) have not been reported. Here, we report that expression level of TFF3 significantly elevated in glioma and correlated with the prognosis of glioma patients. Then we found TFF3 promotes proliferation, invasion, and migration and inhibits apoptosis of glioma cells in vitro, and delayed tumor progression in subcutaneous xenograft nude mice, and prolonged the median survival time in orthotopic xenograft mice. Moreover, knockdown of TFF3 reduced the expression of HIF-1α through a hypoxia-independent manner. These findings suggest that targeting TFF3 may offer a novel strategy for therapeutic intervention of malignant gliomas.

Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore.

In vivo imaging of hormone receptors provides the opportunity to visualize target tissues under hormonal control in live animals. Detecting longer-wavelength photons in the second near-infrared window (NIR-II, 1000-1700 nm) region affords reduced photon scattering in tissues accompanied by lower autofluorescence, leading to higher spatial resolution at up to centimeter tissue penetration depths. Here, we report the conjugation of a small molecular NIR-II fluorophore CH1055 to a follicle stimulating hormone (FSH-CH) for imaging ovaries and testes in live mice. After exposure to FSH-CH, specific NIR-II signals were found in cultured ovarian granulosa cells containing FSH receptors. Injection of FSH-CH allowed live imaging of ovarian follicles and testicular seminiferous tubules in female and male adult mice, respectively. Using prepubertal mice, NIR-II signals were detected in ovaries containing only preantral follicles. Resolving earlier controversies regarding the expression of FSH receptors in cultured osteoclasts, we detected for the first time specific FSH receptor signals in bones in vivo. The present imaging of FSH receptors in live animals using a ligand-conjugated NIR-II fluorophore with low cell toxicity and rapid clearance allows the development of non-invasive molecular imaging of diverse hormonal target cells in vivo.