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In this paper, La2Ce2O7 powders co-activated by Ho3+ and Yb3+ were synthesized by a high temperature solid-state reaction. Both Ho3+ and Yb3+ substitute the La3+ sites in the La2Ce2O7 lattice, where the Ho3+ concentration is 0.5 at.% and the Yb3+ concentration varies in the range of 10~18% at.%. Pumped by a 980 nm laser, the up-conversion (UC) green emission peak at 547 nm and the red emission at 661 nm were detected. When the doping concentration of Ho3+ and Yb3+ are 0.5 at.% and 14% at.%, respectively, the UC emission reaches the strongest intensity. The temperature-sensing performance of La2Ce2O7:Ho3+ with Yb3+ was studied in the temperature range of 303–483 K, where the highest relative sensitivity (Sr) is 0.0129 K−1 at 483 K. The results show that the powder La2Ce2O7:Ho3+, Yb3+ can be a potential candidate for remote temperature sensors.

Graphitized carbon nitride (g-C3N4), as a metal-free, visible-light-responsive photocatalyst, has a very broad application prospect in the fields of solar energy conversion and environmental remediation. The g-C3N4 photocatalyst owns a series of conspicuous characteristics, such as very suitable band structure, strong physicochemical stability, abundant reserves, low cost, etc. Research on the g-C3N4 or g-C3N4-based photocatalysts for real applications has become a competitive hot topic and a frontier area with thousands of publications over the past 17 years. In this paper, we carefully reviewed the recent advances in the synthesis and structural design of g-C3N4 materials for efficient photocatalysts. First, the crucial synthesis parameters of g-C3N4 were fully discussed, including the categories of g-C3N4 precursors, reaction temperature, reaction atmosphere and reaction duration. Second, the construction approaches of various nanostructures were surveyed in detail, such as hard and soft template, supramolecular preorganization and template-free approaches. Third, the characteristics of different exfoliation methods were compared and summarized. At the end, the problems of g-C3N4 materials in photocatalysis and the prospect of further development were disclosed and proposed to provide some key guidance for designing more efficient and applicable g-C3N4 or g-C3N4-based photocatalysts.

Abstract Ratiometric luminescence thermometry with trivalent lanthanide ions and their 4f n energy levels is an emerging technique for non-invasive remote temperature sensing with high spatial and temporal resolution. Conventional ratiometric luminescence thermometry often relies on thermal coupling between two closely lying energy levels governed by Boltzmann’s law. Despite its simplicity, Boltzmann thermometry with two excited levels allows precise temperature sensing, but only within a limited temperature range. While low temperatures slow down the nonradiative transitions required to generate a measurable population in the higher excitation level, temperatures that are too high favour equalized populations of the two excited levels, at the expense of low relative thermal sensitivity. In this work, we extend the concept of Boltzmann thermometry to more than two excited levels and provide quantitative guidelines that link the choice of energy gaps between multiple excited states to the performance in different temperature windows. By this approach, it is possible to retain the high relative sensitivity and precision of the temperature measurement over a wide temperature range within the same system. We demonstrate this concept using YAl3(BO3)4 (YAB):Pr3+, Gd3+ with an excited 6P J crystal field and spin-orbit split levels of Gd3+ in the UV range to avoid a thermal black body background even at the highest temperatures. This phosphor is easily excitable with inexpensive and powerful blue LEDs at 450 nm. Zero-background luminescence thermometry is realized by using blue-to-UV energy transfer upconversion with the Pr3+−Gd3+ couple upon excitation in the visible range. This method allows us to cover a temperature window between 30 and 800 K.

The degradation of aflatoxin (AF) is a topic that always exists along with the food and feed industry. Photocatalytic degradation as an advanced oxidation technology has many benefits, including complete inorganic degradation, no secondary contamination, ease of activity under moderate conditions, and low cost compared with traditional physical, chemical, and biological strategies. However, photocatalysts are usually dispersed during photocatalytic reactions, resulting in energy and time consumption in the separation process. There is even a potential secondary pollution problem from the perspective of food safety. In this regard, three electrospun membranes anchored with g-C3N4/MoS2 composites were prepared for highly efficient photocatalytic degradation of aflatoxin B1 (AFB1) under visible light. These photocatalytic membranes were characterized by XRD, SEM, TEM, FTIR, and XPS. The factors influencing the degradation efficiency of AFB1, including pH values and initial concentrations, were also probed. The three kinds of photocatalytic membranes all exhibited excellent ability to degrade AFB1. Among them, the photocatalytic degradation efficiency of the photocatalytic membranes prepared by the coaxial methods reached 96.8%. The experiment is with an initial concentration of 0.5 μg/mL (500 PPb) after 60 min under visible light irradiation. The mechanism of degradation of AFB1 was also proposed based on active species trapping experiments. Moreover, the prepared photocatalytic membranes exhibited excellent photocatalytic activity even after five-fold use in the degradation of AFB1. These studies showed that electrospun membranes anchored with g-C3N4/MoS2 composites have a high photocatalytic ability which is easily removed from the reacted medium for reuse. Thereby, our study offers a highly effective, economical, and green solution for AFB1 degradation in the foodstuff for practical application.

Therapeutic antibodies targeting vascular endothelial growth factor (VEGF) have become a critical regimen for tumor therapy, but the efficacy of monotherapy is usually limited by drug resistance and multiple angiogenic mechanisms. Complement proteins are becoming potential candidates for cancer-targeted therapy based on their role in promoting cancer progression and angiogenesis. However, the antitumor abilities of simultaneous VEGF and complement blockade were unknown. We generated a humanized soluble VEGFR-Fc fusion protein (VID) binding VEGFA/PIGF and a CR1-Fc fusion protein (CID) targeting C3b/C4b. Both VID and CID had good affinities to their ligands and showed effective bioactivities. In vitro, angiogenesis effects induced by VEGF and hemolysis induced by complement were inhibited by VID and CID, respectively. Further, VID and CID confer a synergetic therapeutic effect in a colitis-associated colorectal cancer (CAC) model and an orthotopic 4T1 breast cancer model. Mechanically, combination therapy inhibited tumor angiogenesis, cell proliferation, and MDSC infiltration in the tumor microenvironment and promoted tumor cell apoptosis. Our study offers a novel therapeutic strategy for anti-VEGF-resistant tumors and chronic-inflammation-associated tumors. Keywords: VEGFR-Fc fusion protein, CR1-Fc fusion protein, combination therapy, angiogenesis, MDSCs

Abstract Background Ischemic vascular diseases are the major cause of death worldwide. In recent years, endothelial cell (EC)-based approaches to vascular regeneration are increasingly viable strategies for treating ischemic diseases, but their applications are challenged by the difficulties in their efficient generation and stable maintenance. Here, we show an alternative protocol that facilitates the generation of functional and expandable ETS variant 2 (ETV2)-induced endothelial-like cells (EiECs) from human adipose-derived stem cells (hADSCs), providing a potential source of cells for autologous ECs to treat ischemic vascular diseases. Methods hADSCs were obtained from fresh human adipose tissue. Passage 3 hADSCs were transduced with doxycycline (DOX)-inducible ETV2 transcription factor; purified ETV2-hADSCs were induced into endothelial-like cells using a two-stage induction culture system composed of small molecule compounds and cell factors. EiECs were evaluated for their surface markers, proliferation, gene expression, secretory capacity, and effects on vascular regeneration in vivo. Results We found that short-term ETV2 expression combined with TGF-β inhibition is sufficient for the generation of kinase insert domain receptor (KDR)+ cells from hADSCs within 10 days. KDR+ cells showed immature endothelial characteristics, and they can gradually mature in a chemically defined induction medium at the second stage of induction. Futher studies showed that KDR+ cells deriving EC-like cells could stably self-renew and expand about 106-fold in 1 month, and they exhibited expected genome-wide molecular features of mature ECs. Functionally, these EC-like cells significantly promoted revascularization in a hind limb ischemic model. Conclusions We isolated highly purified hADSCs and effectively converted them into functional and expandable endothelial-like cells. Thus, the study may provide an alternative strategy to obtain functional EC-like cells with potential for biomedical and pharmaceutical applications.

Following publication of the original article [1], the authors reported an error in Fig 5 of this article, graphs presenting FCM and immunofluorescent for CD4T, CD8T and NK cell of the Control Groups (LL2, LL2-irradation, MCS-irradiation) were inadvertently duplicated from another parallel experiment.

Abstract SARI, also called as BATF2, belongs to the BATF family and has been implicated in cancer cell growth inhibition. However, the role and mechanism of SARI in tumour angiogenesis are elusive. Here we demonstrate that SARI deficiency facilitates AOM/DSS-induced colonic tumorigenesis in mice. We show that SARI is a novel inhibitor of colon tumour growth and angiogenesis in mice. Antibody array and HUVEC-related assays indicate that VEGF has an essential role in SARI-controlled inhibition of angiogenesis. Furthermore, Co-IP/PAGE/mass spectrometry indicates that SARI directly targets ceruloplasmin (Cp), and induces protease degradation of Cp, thereby inhibiting the activity of the HIF-1α/VEGF axis. Tissue microarray results indicate that SARI expression inversely correlates with poor clinical outcomes in colon cancer patients. Collectively, our results indicate that SARI is a potential target for therapy by inhibiting angiogenesis through the reduction of VEGF expression and is a prognostic indicator for patients with colon cancer.

Abstract Background Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. Tumor cells genetically modified to secrete immune activating cytokines have been proved to be more immunogenic. IL-18 could augment proliferation of T cells and cytotoxicity of NK cells. GM-CSF could stimulate dendritic cells, macrophages and enhance presentation of tumor antigens. In our study, we used mouse GM-CSF combined with IL-18 to modify Lewis lung cancer LL/2, then investigated whether vaccination could suppress tumor growth and promote survival. Methods The Lewis lung cancer LL/2 was transfected with co-expressing mouse GM-CSF and IL-18 plasmid by cationic liposome, then irradiated with a sublethal dose X ray (100 Gy) to prepare vaccines. Mice were subcutaneously immunized with this inactivated vaccine and then inoculated with autologous LL/2 to estimate the antitumor efficacy. Results The studies reported here showed that LL/2 tumor cell vaccine modified by a co-expressing mouse GM-CSF and IL-18 plasmid could significantly inhibit tumor growth and increased survival of the mice bearing LL/2 tumor whether prophylactic or adoptive immunotherapy in vivo. A significant reduction of proliferation and increase of apoptosis were also observed in the tumor treated with vaccine of co-expressing GM-CSF and IL-18. The potent antitumor effect correlated with higher secretion levels of pro-inflammatory cytokines such as IL-18, GM-CSF, interferon-γ in serum, the proliferation of CD4+ IFN-γ+, CD8+ IFN-γ+ T lymphocytes in spleen and the infiltration of CD4+, CD8+ T in tumor. Furthermore, the mechanism of tumor-specific immune response was further proved by 51Cr cytotoxicity assay in vitro and depletion of CD4, CD8, NK immune cell subsets in vivo. The results suggested that the antitumor mechanism was mainly depended on CD4+, CD8+ T lymphocytes. Conclusions These results provide a new insight into therapeutic mechanisms of IL-18 plus GM-CSF modified tumor cell vaccine and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity.

Background: Desmoid fibromatosis (DF) is a pathological intermediate fibroblastoma that is difficult to control locally due to its invasive nature, especially in the extremities. Although anlotinib demonstrated efficacy in treating DF with tolerable safety, the impact of surgical intervention in conjunction with anlotinib administration on local control in patients with extremity DF remains undetermined.Methods: We conducted a retrospective examination of the clinical medical documentation belonging to patients with resectable DF of the extremities who were treated with surgery between January 2010 and June 2022. The patients were divided into two cohorts: surgery alone cohort and surgery combined with anlotinib group (surgery plus anlotinib cohort), crossover to surgery plus anlotinib cohort was admissible for patients in the surgery alone cohort who experienced disease recurrence postoperatively. Clinical data such as basic information, tumor location, anlotinib toxicity, time to recurrence, surgical complications, follow-up time, visual analogue scale (VAS) score and Musculoskeletal Tumor Society (MSTS) score at the last follow-up were collected.Results: In total, 48 consecutive patients (19 males and 29 females) with resectable DF of the extremities, including 25 patients in the surgery alone cohort, 23 patients in the surgery plus anlotinib cohort, and 10 patients who were transferred from the surgery alone cohort to the surgery plus anlotinib cohort. The VAS score at the last follow-up was 5 (IQR, 3–6) in the surgery alone cohort and 2 (IQR, 1–3) in the surgery plus anlotinib cohort, respectively; the MSTS score at the last follow-up was 19 (IQR, 16.5–24) in the surgery alone cohort and 27 (IQR, 25–28) in the surgery plus anlotinib cohort, respectively; these characteristics were statistically different between the two cohorts. The 3-year recurrence-free survival (RFS) of the surgery alone cohort and the surgery plus anlotinib cohort were 37.7% and 72.6%, respectively, and the difference was statistically significant (p = 0.022).Conclusion: Surgery combined with anlotinib appears to be effective in controlling local recurrence in patients with resectable DF of the extremities, and the side effects were acceptable.

PurposeLimb salvage surgery and amputation are two commonly performed procedures for lower extremity tumors. When comparing these procedures in tumor patients, it is important to consider their impact on quality of life (QOL) and functional mobility. These patients often experience physical, emotional, and psychological challenges, making these factors crucial in determining the most suitable treatment approach.MethodThe outcomes of lower extremity tumors patients for QOL were collected from PubMed, MEDLINE, EMBASE, Cochrane, and Google Scholar until 28 February 2023. The physical function, mental health, role function, social function, emotional function, Toronto Extremity Salvage Score, and Musculoskeletal Tumor Society Score outcomes were analyzed to determine the differences between the two procedures.ResultsFive articles were included according to the selection criteria with a total of 245 patients. The standard mean difference (SMD) values of each parameter were slightly higher in limb salvage surgery patients but not higher enough to produce statistically significant results; the SMD values for physical function and mental health were 0.72 and 0.04, respectively. This study did not report any heterogeneity or publication bias.ConclusionsQOL is a large and enhanced term, which carries its importance and is challenging to compare between any procedures. The minimal rise in SMD of different QOL parameters highlighted only a slight advantage of limb salvage surgery over amputation. Therefore, further research is required to explore the impact of this crucial topic.

IntroductionGait analysis is one of the most important components of functional outcome evaluation in patients with lower-extremity tumors. Disparities between operated limbs when compared with non-operated limbs and healthy populations based on gait parameters have rarely been studied. In the present study, we attempted to analyze the gait difference and its impacts on daily life.MethodsThe gait parameters of distal femoral tumor-resected patients were collected from PubMed, CNKI, MEDLINE, Embase, Cochrane, and Google Scholar till September 30, 2022, by strictly following the inclusion and exclusion criteria. Differences between gait parameters in the operated and non-operated limbs or healthy limbs of distal femoral tumor patients were analyzed based on stance phase, swing phase, cadence, and velocity. The fixed-effects and random-effects models were used to conduct a meta-analysis.ResultsSix studies were included according to the selection criteria. There were 224 patients in total in these studies. Standard mean differences were calculated for all of our outcomes. Our results showed that there was a minimal difference in the standard mean difference of gait parameters between operated and non-operated limbs and healthy limbs.ConclusionDistal femoral tumor resections have been associated with deficient muscle function and strength and impaired gait parameters. Minimal differences in the gait parameters highlighted the advantage of distal femoral resection when replaced with a prosthesis.

Objective Soft tissue sarcomas (STSs) arising from the popliteal fossa pose surgical challenges due to their proximity to critical neurovascular structures. This study aimed to investigate whether a novel 3D imaging technique highlighting these key anatomical structures could facilitate preoperative planning and improve surgical outcomes in STS. Methods This was a prospective, observational, pilot study. Between November 2019 and December 2020, 27 patients with STS of the popliteal fossa undergoing limb‐sparing procedures were enrolled and assigned to either a control or intervention group. Control patients underwent traditional preoperative planning with separate computed tomography angiography, magnetic resonance imaging, and magnetic resonance hydrography. In the intervention group, 3D images were generated from these images, the tumor and skeletomuscular and neurovascular structures were revealed in three dimensions, and this was visualized on the surgeon's smartphone or computer. Primary endpoints were surgical margins and complications. Secondary endpoints included operative time, blood loss, serum C‐reactive protein and interleukin‐6, length of in‐hospital stay, and limb function. Comparisons between groups were made using independent‐sample t‐tests for continuous data and the Mann–Whitney U and Fisher's exact tests for categorical data. Results There was a lower but not significantly different inadvertent positive margin rate (1/15 vs. 3/12, P = 0.294), significantly shorter hospital stay (P = 0.049), and less numbers ≥75th percentile of operative time (P = 0.037) and blood loss (P = 0.024) in the intervention group. Differences in surgical complications, operative time, blood loss, C‐reactive protein and interleukin‐6 levels on the second postoperative day, and limb functional scores were statistically insignificant. Conclusions The novel 3D imaging technique facilitates complex preoperative planning and limb‐salvage surgical procedures for patients with STS of the popliteal fossa, and this may affect how surgical planning is performed in the future.

BackgroundCurrent research is focused on the factors that influence the maintenance of limb function after total femoral replacement. This retrospective study investigated the difference in functional outcomes in patients with invasion of the rectus femoris vs. an intact rectus femoris that underwent total femoral replacement with a modular total femur prosthesis.MethodsThe medical records of patients who underwent total femoral replacement with a modular total femur prosthesis between July 2010 and March 2017 at our institute were retrospectively reviewed. The patients were divided into two groups: group A had invasion of the rectus femoris and group B had an intact rectus femoris. Functional status was assessed using the Musculoskeletal Tumor Society Rating Scale (MSTS) and the Harris Hip Score (HHS). Complications were assessed using the International Society of Limb Salvage classification that was published in 2011 and modified in 2014.ResultsThe mean total MSTS score (23.0 ± 4.8 vs. 17.6 ± 3.1; P = 0.02) and the mean total HHS score (80.17 ± 6.24 vs. 55.38 ± 13.30; P = 0.001) were significantly higher in patients with intact rectus femoris compared with patients with invasion of the rectus femoris. Patients with an intact rectus femoris achieved significantly better limb function (support and gait) and active range of motion (P < 0.05). The overall complication rate was 35.7%.ConclusionsFunctional outcomes after total femoral replacement were significantly better in patients with an intact rectus femoris compared with patients with invasion of the rectus femoris, possibly because more muscle mass can be preserved around the femur in patients with an intact rectus femoris.

IntroductionMalignant and giant pelvic tumors are complex and rare, and hemipelvectomies are complex procedures performed for this malignant lesion. Only a few studies had been conducted on the survival and recurrence of pelvic sarcomas patients undergoing internal or external hemipelvectomy. In the present study, we compared internal with external hemipelvectomy in pelvic sarcomas on clinical outcomes by a meta-analysis.MethodsThe survival and recurrence rates of pelvic sarcomas patients were collected from research reports from CNKI, MEDLINE, EMBASE, the Cochrane Database, and Google Scholar until April 2022. The quality of included articles was evaluated by two independent reviewers. Differences between patients undergoing internal and external hemipelvectomy were analyzed based on postoperative survival and recurrence rates.ResultsFive articles were included according to selection criteria. There were 183 patients in total from these studies. Our results showed that there was no significant difference between limb salvage surgery and amputation according to survival; however, patients with internal hemipelvectomy had a lower recurrence rate.ConclusionsInternal hemipelvectomy results in a lower recurrence rate and similar survival rate, while not increasing the risk of metastasis and complications. This study provided more pieces of evidence to support internal hemipelvectomy as a favorable treatment of pelvic sarcomas.

Background: The restoration and reconstruction of patello-femoral large osteochondral defects caused by bone tumours are challenging because of the local recurrence rate and the joint’s mechanical complexity. Although three-dimensional (3D)-printed prostheses are commonly adopted for tumour-induced bone defect reconstruction, patello-femoral osteochondral reconstruction with 3D-printed prostheses is rarely reported.Case presentation: A 44-year-old female patient with progressive swelling and pain in the left knee for 6 months was diagnosed with Campanacci Grade II giant cell tumour (GCT). She underwent intralesional curettage combined with autografting and internal fixation, after which complications of deep infection arose. The patient then underwent internal fixation removal and cement packing. Afterwards, the pain of the affected knee persisted for 11 months, and bone cement removal plus 3D-printed modular prosthesis reconstruction was performed. At the last follow-up 27 months after surgery, she was pain free, the Musculoskeletal Tumour Society (MSTS) score improved from 15/30 to 29/30, the Visual Analogue Scale (VAS) score decreased from 7 to 0, and knee flexion increased from 50° to 130°. X-ray images 22 months after surgery showed that the prosthesis and screws were in a stable position, and callus formation was found at the prosthesis-bone interface.Conclusions: A 3D-printed modular prosthesis may be a useful treatment option for the surgical reconstruction of GCT-induced patello-femoral large osteochondral defects. The firm fixation, osseointegration, and favourable congruency of the 3D-printed prosthesis with the adjacent articular surface can achieve long-term knee function and stability.

BackgroundPrevious studies have showed that single nucleotide polymorphisms (SNPs) might be implicated in the pathogenesis of osteosarcoma (OS). Numerous studies involving SNPs with OS risk have been reported; these results, however, remain controversial and no comprehensive research synopsis has been performed till now.ObjectiveThis study seeks to clarify the relationships between SNPs and OS risk using a comprehensive meta-analysis, and assess epidemiological evidence of significant associations.MethodsThe PubMed, Web of Science, and Medline were used to screen for articles that evaluated the association between SNP and OS susceptibility in humans before 24 December 2021. Furthermore, we used Venice Criteria and a false positive report probability (FPRP) test to assess the grades of epidemiological evidence for the statistical relationships.ResultsWe extracted useful data based on 43 articles, including 10,255 cases and 13,733 controls. Our results presented that 25 SNPs in 17 genes were significantly associated with OS risk. Finally, we graded strong evidence for 17 SNPs in 14 genes with OS risk (APE1 rs1760944, BCAS1 rs3787547, CTLA4 rs231775, ERCC3 rs4150506, HOTAIR rs7958904, IL6 rs1800795, IL8 rs4073, MTAP rs7023329 and rs7027989, PRKCG rs454006, RECQL5 rs820196, TP53 rs1042522, VEGF rs3025039, rs699947 and rs2010963, VMP1 rs1295925, XRCC3 rs861539), moderate for 14 SNPs in 12 genes and weak for 14 SNPs in 11 genes.ConclusionIn summary, this study offered a comprehensive meta-analysis between SNPs and OS susceptibility, then evaluated the credibility of statistical relationships, and provided useful information to identify the appropriate candidate SNPs and design future studies to evaluate SNP factors for OS risk.

Hemiarthroplasty and total hip arthroplasty are routinely performed procedures. A comparison of these procedures in tumor patients can be performed based on complications and functional outcomes. To weigh the advantages and disadvantages of both procedures, a comparative study is indeed required to decide which procedure is more beneficial for primary bone tumor patients. The outcomes of proximal femur tumor-resected patients were collected from research reports from PubMed, MEDLINE, EMBASE, Cochrane, and Google Scholar until 30 December 2022. Differences between these two operative procedures in primary bone tumors patients were analyzed based on dislocation, infection, local recurrence, MSTS, and HHS. Six articles were included according to the selection criteria with a total of 360 patients. Our results showed that there was a significant difference in our primary outcome as hemiarthroplasty participants encountered less dislocation than those with total hip arthroplasty. Moreover, the secondary outcomes of our study were similar. Proximal femur bone tumors, when resected, tend to produce more complications and decrease functional ability due to extensive tumor extension and soft tissue involvement. The lower dislocation rate in hemiarthroplasty participants emphasizes the importance of preserving the acetabular head in hemiarthroplasty as a key to preventing dislocation.

Abstract Objective To analyse the anatomical conditions of transverse sacroiliac screw (TSS) about the S1 and S2 segments in order to develop and validate a locked navigational template for TSS placement. Methods A total of 22 patients with sacral fractures were involved in this study from May 2018 to February 2019. Patients were divided into two groups according to the surgery procedure: locked template group and conventional group. The CT data of 90 normal sacra were analysed. The long axis, short axis and lengths of TSS, cancellous corridors were measured through 3D modelling. A patient-specific locked navigation template based on simulated screws was designed and 3D printed and then used to assist in TSS placement. The operative time and radiation times were recorded. The Matta criteria and grading score were evaluated. The entry point deviation of the actual screw placement relative to the simulated screw placement was measured, and whether the whole screw was in the cancellous corridor was ob`served. Results S1 screws with a diameter of 7.3 mm could be inserted into 69 pelvises, and S2 screws could be inserted in all pelvises. The S1 cancellous corridor had a long axis of 25.44 ± 3.32 mm in males and 22.91 ± 2.46 mm in females, a short axis of 14.21 ± 2.19 mm in males and 12.15 ± 3.22 mm in females, a corridor length of 153.07 ± 11.99 mm in males and 151.11 ± 8.73 mm in females, and a proportional position of the optimal entry point in the long axis of the cancellous corridor of 35.96 ± 10.31% in males and 33.28 ± 7.2% in females. There were significant differences in the corridor long axis and corridor short axis between sexes (p < 0.05), and there were no significant differences in corridor length and proportional position of the optimal entry point in the long axis of the cancellous corridor between sexes (p > 0.05). The S2 cancellous corridor had a long axis of 17.58 ± 2.36 mm in males and 16 ± 2.64 mm in females, a short axis of 14.21 ± 2.19 mm in males and 13.14 ± 2.2 mm in females, a corridor length of 129.95 ± 0.89 mm in males and 136.5 ± 7.96 mm in females, and a proportional position of the optimal entry point in the long axis of the cancellous corridor of 46.77 ± 9.02% in males and 42.25 ± 11.95% in females. There were significant differences in the long axis, short axis and corridor length (p < 0.05). There was no significant difference in the proportional position of the optimal entry point in the long axis of the cancellous corridor (p > 0.05). A total of 20 transversal sacroiliac screws were successfully implanted into 10 patients with the assistance of locked navigation templates, and a total of 24 transversal sacroiliac screws were successfully implanted into 12 patients under C-arm fluoroscopy. There was a significant difference in surgical time (88 ± 14.76 min vs 102.5 ± 17.12 min, p = 0.048), radiation times (11.5 ± 1.78 vs 54.83 ± 6.59, p < 0.05) and screw grading between two groups (nineteen screws in grade 0, one screw in grade 1 and 0 screws in grade 2 vs fourteen screws in grade 0, 8 screws in grade 1 and 2 screws in grade 2, p = 0.005). All screw entry point deviations were shorter than the short axis of the cancellous corridor, and all screws were located completely within the cancellous corridor. Conclusion Approximately 76% of males and females can accommodate screws with diameters of 7.3 mm in S1, and all persons can accommodate the same screw in S2. From the standard lateral perspective of the sacrum, the optimal entry point of the transverse screw is in the first 1/3 of the cancellous corridor for S1 and the centre of the cancellous corridor for S2. The patient-specific locked navigation template assisted in TSS placement with less operative time, less intraoperative fluoroscopy and higher safety of screw placement compared with traditional surgery.

Abstract Objective To evaluate the accuracy of percutaneous pedicle screw (PPS) placement aided by a new drill guide template. Methods The patients were divided into guide template group and conventional perspective group. In the conventional perspective group, the screws were placed by hand under fluoroscopy. In the guide template group, the screw placement was aided by a new drill guide template, and the drill guide template is designed according to the patient's ideal pedicle screw, but not based on skin morphology. The accuracy was evaluated by comparing the following parameters between the two groups: pedicle breach level, inclination angle deviation between the left and right screws, sagittal angle deviation between the left and right screws, and position deviation of the left and right screw entry points. The consistency of the postoperative screw angle and the corresponding guide template inclination angle was compared in the guide template group. The operative time, blood loss, and radiation times were compared between the groups. Results A total of 146 patients (876 screws) were enrolled in our study including 79 (474 screws) in the guide template group and 67 (402 screws) in the conventional perspective group. The pedicle breach level in the guide template group (22/474) was significantly lower than that in the conventional perspective group (47/402) (P

Background: Liver disease is a major cause of death worldwide. Orthotropic liver transplantation (OLT) represents the only effective treatment for patients with liver failure, but the increasing demand for organs is unfortunately so great that its application is limited. Hepatocyte transplantation is a promising alternative to OLT for the treatment of some liver-based metabolic disorders or acute liver failure. Unfortunately, the lack of donor livers also makes it difficult to obtain enough viable hepatocytes for hepatocyte-based therapies. Currently, a fundamental solution to this key problem is still lacking. Here we show a novel non-transgenic protocol that facilitates the rapid generation of functional induced hepatocytes (iHeps) from human adipose-derived stem cells (hADSCs), providing a source of available cells for autologous hepatocytes to treat liver disease. Methods: We used collagenase digestion to isolate hADSCs. The surface marker was detected by flow cytometry. The multipotential differentiation potency was detected by induction into adipocytes, osteocytes, and chondrocytes. Passage 3-7 hADSCs were induced into iHeps using an induction culture system composed of small molecule compounds and cell factors. Results: Primary cultured hADSCs presented a fusiform or polygon appearance that became fibroblast-like after passage 3. More than 95 % of the cells expressed the mesenchymal cell markers CD29, CD44, CD166, CD105, and CD90. hADSCs possessed multipotential differentiation towards adipocytes, osteocytes, and chondrocytes. We rapidly induced hADSCs into iHeps within 10 days in vitro; the cellular morphology changed from fusiform to close-connected cubiform, which was similar to hepatocytes. After induction, most of the iHeps co-expressed albumin and alpha-1 antitrypsin; they also expressed mature hepatocyte special genes and achieved the basic functions of hepatocyte. Moreover, iHep transplantation could improve the liver function of acute liver-injured NPG mice and prolong life. Conclusions: We isolated highly purified hADSCs and rapidly induced them into functional hepatocyte-like cells within 10 days. These results provide a source of available cells for autologous hepatocytes to treat liver disease. [ABSTRACT FROM AUTHOR]

The generation of functional hepatocytes is a major challenge for regenerative medicine and drug discovery. Here we show a method that facilitates generation of induced functional hepatocytes (iHeps) from adipose-derived stem cells (ADSCs) within 9 days. iHeps express hepatocytic gene programs and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity. Upon transplantation into mice with carbon tetrachloride (CCl4)-induced acute fulminant liver failure, iHeps restore the liver function and prolong survival. The work could contribute to the development of alternative strategies to obtain nonhepatic cell-derived mature hepatocytes with potential for biomedical and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Axillary soft tissue sarcoma (STS) is challenging due to its proximity to vital neurovascular bundles. We conducted a prospective observational pilot study to explore whether 3D multimodality imaging (3DMMI) can improve preoperative planning for and surgical outcomes of patients with axillary STS. Twenty-one patients with STS (diameter > 5 cm) of the axilla were allocated, at their discretion, to either a control group undergoing traditional preoperative planning with separate computed tomography angiography, magnetic resonance imaging, and magnetic resonance neurography, or an intervention group where 3DMMI, digitally created based on these images, revealed the tumour and adjacent skeletomuscular and neurovascular structures in three dimensions. Primary outcome measures were surgical margins and surgical complications. Secondary outcomes included operative time, blood loss, serum C-reactive protein and interleukin-6, length of hospital stay, and limb function. The 3DMMI group had a lower, although not significantly different, inadvertent positive margin rate (1/12 vs. 3/9, p = 0.272), a significantly shorter operative time (p = 0.048), reduced blood loss (p = 0.038), and reduced length of hospital stay (p = 0.046). This endorses larger trials to improve complex surgical procedures and study how preoperative planning could be performed in the future.

Background Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. Tumor cells genetically modified to secrete immune activating cytokines have been proved to be more immunogenic. IL-18 could augment proliferation of T cells and cytotoxicity of NK cells. GM-CSF could stimulate dendritic cells, macrophages and enhance presentation of tumor antigens. In our study, we used mouse GM-CSF combined with IL-18 to modify Lewis lung cancer LL/2, then investigated whether vaccination could suppress tumor growth and promote survival. Methods The Lewis lung cancer LL/2 was transfected with co-expressing mouse GM-CSF and IL-18 plasmid by cationic liposome, then irradiated with a sublethal dose X ray (100Gy) to prepare vaccines. Mice were subcutaneously immunized with this inactivated vaccine and then inoculated with autologous LL/2 to estimate the antitumor efficacy. Results The studies reported here showed that LL/2 tumor cell vaccine modified by a co-expressing mouse GM-CSF and IL-18 plasmid could significantly inhibit tumor growth and increased survival of the mice bearing LL/2 tumor whether prophylactic or adoptive immunotherapy in vivo. A significant reduction of proliferation and increase of apoptosis were also observed in the tumor treated with vaccine of co-expressing GM-CSF and IL-18. The potent antitumor effect correlated with higher secretion levels of pro-inflammatory cytokines such as IL-18, GM-CSF, interferon-γ in serum, the proliferation of CD4+IFN-γ +, CD8+ IFN-γ + T lymphocytes in spleen and the infiltration of CD4+, CD8+ T in tumor. Furthermore, the mechanism of tumor-specific immune response was further proved by 51Cr cytotoxicity assay in vitro and depletion of CD4, CD8, NK immune cell subsets in vivo. The results suggested that the antitumor mechanism was mainly depended on CD4+, CD8+ T lymphocytes. Conclusions These results provide a new insight into therapeutic mechanisms of IL-18 plus GM-CSF modified tumor cell vaccine and provide a potential clinical cancer immunotherapeutic agent for improved antitumor immunity. [ABSTRACT FROM AUTHOR]

A new VEGF receptor fusion protein FP3 was shown to have promising antitumor potency better than Bevacizumab. Characterization of its immune response is essential to the safe and effective administration in clinical trials. In this study, both BIACORE and ELISA assays were employed to assess pre-clinical immunogenicity of FP3 in monkeys. Serum samples from 20 rhesus monkeys were analyzed for the generation of anti-FP3 antibody after intravenous administration of three doses of FP3 ( n = 6 per group) or buffer control ( n = 2). Sera samples were obtained at 2, 4, 6, 8, 10 weeks after the first administration. It showed BIACORE presented linear correlation with the dilution of anti-FP3 antibody and the results of ELISA. Two weeks after the initial FP3 injection, anti-FP3 antibody was detected in about 20% FP3-treated monkeys. The ratio of positive samples and the titer of antibody increased along with the FP3-treatment time. Six weeks following FP3 injection almost all the samples were anti-FP3 antibody positive. Moreover, the titer of anti-FP3 antibody but not the ratio of positive samples was also enhanced when the dose of FP3 was elevated. Furthermore, the immunoglobulin types and subclasses of anti-FP3 antibody serum components were mainly identified as IgG1 and IgG4, not IgM. Serum antibodies are characterized that they could not block FP3 binding to VEGF and were non-neutralizing. Our data implied that proteins with full human sequences may also have the potential to induce immune response in rhesus monkeys, and BIACORE could be an effective approach to detect the immunogenicity of protein therapeutics in clinic. [ABSTRACT FROM AUTHOR]

Abstract Purpose  KH902, a recombinant fusion protein, is designed for treatment of neovascular age-related macular degeneration. The study is to investigate the prevention efficacy of KH902 on experimental choroidal neovascularization (CNV) in a monkey model. Materials and Methods  Binding assay and endothelial cell proliferation assay were used to evaluate activity and bioactivity of KH902 in vitro while an initial comparison of bioactivity was made between KH902 and Ranizumab (Lucentis). Ocular and systemic levels of KH902 were analyzed by enzyme-linked immunosorbent assay (ELISA) method after single intravitreal administration to evaluate its availability to ocular fundus. In vivo pharmacological study, CNV was induced by laser in monkeys and KH902 prevention efficacy on CNV was evaluated by incidence of CNV and several ophthalmic examinations. Results  KH902 is a unique fusion protein with high affinity to VEGF and good availability to target tissue, beneficial to good bioactivity in vivo. In vivo pharmacological study, the incidence of CNV formation was largely reduced in KH902 treatment groups. Furthermore, the leakage of CNV in control group which crossed over to KH902 treatment 40 days after laser was much less than that before KH902 treatment. Conclusion  KH902 was effective to prevent the formation of experimental CNV and also to treat pre-existed CNV without evidence of toxicity. This study suggests that KH902 has promise as a local anti-angiogenic treatment of CNV-related diseases. [ABSTRACT FROM AUTHOR]

A novel chitosan hydrogel with high porosity was fabricated by a crosslinking method. Cartilage tissue engineering formed after mesenchymal stem cells was cultured on this hydrogel scaffold for 12 weeks. The immunohistochemistry tests demonstrated that the obtained cartilage had the specific histological properties of natural cartilage. And the qPCR tests also proved that the genes for type II collagen in the obtained cartilage were expressed the same as in the natural one.

IL-35 downregulates Th17 cell development and suppresses certain types of autoimmune inflammation such as collagen-induced arthritis and experimental autoimmune uveitis. Psoriasis is thought to be initiated by abnormal interactions between cutaneous keratinocytes and systemic immune cells. However, the role of IL-35 in psoriasis remains unclear. In this study, we assessed IL-35 in three well-known psoriasis models: a human keratinocyte cell line (HaCaT), a keratin 14 (K14)-vascular endothelial growth factor A (VEGF-A)-transgenic (Tg) mouse model, and an imiquimod-induced psoriasis mouse model. First, we found that IL-35 suppressed the expression of IL-6, CXCL8, and S100A7, which are highly upregulated by a mixture of five proinflammatory cytokines in HaCaT. Second, a plasmid coding for the human IL-35 sequence coated with cationic liposomes showed potent immunosuppressive effects on K14-VEGF-A-Tg and imiquimod-induced psoriasis mouse models. In the K14-VEGF-A-Tg model, our results showed that several types of proinflammatory cytokines were significantly reduced, whereas IL-10 was remarkably induced by IL-35. Compared with pcDNA3.1, there was a small number of CD4+IL-17+ T cells and a large number of CD4+IL-10+ and CD4+CD25+Foxp3+ T cells in the IL-35 group. Most importantly, we found that IL-35 decreased the total number of macrophages and ratio of M1/M2 macrophages, which has not been reported previously. In addition, compared with dexamethasone, IL-35 showed long-term therapeutic efficacy. In summary, our results strongly indicate that IL-35 plays a potent immunosuppressive role in psoriasis. Thus, IL-35 has potential for development as a new therapeutic strategy for patients with chronic psoriasis and other cutaneous inflammatory diseases. [ABSTRACT FROM AUTHOR]