Correlation of IVIM/DKI Parameters with Hypoxia Biomarkers in Fibrosarcoma Murine Models: Direct Control of MRI and Pathological Sections.

RATIONALE AND OBJECTIVES: To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. MATERIALS AND METHODS: A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. RESULTS: The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. CONCLUSION: IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia.

Enhanced Sensing Performance of SnX Ti1-X O2 -TiX Sn1-X O2 Core-Shell Heterostructure via Increasing the Density of Unsaturated Sn and Ti Atoms.

The strategy of combining different semiconductor materials is adjudged an effective approach to improve the sensing performances of semiconductor materials. However, the specific synergistic mechanism for the excellent gas-sensitive performances of composite materials has not been elucidated. Herein, a facile solvothermal method is employed to synthesize SnX Ti1-X O2 -TiX Sn1-X O2 core-shell heterostructures using SnCl4 •5H2 O and tetrabutyl titanate (TBOT) as raw materials. When the molar ratio of SnCl4 •5H2 O/TBOT is 1.8/3.0, the afforded composite exhibited the highest gas sensing performances compared with other composites prepared with other molar ratios. The enhanced sensing performance is attributed to the simultaneous incorporation of Sn and Ti ions into each other's lattice, leading to an increase in the density of unsaturated Sn and Ti atoms on the surface. Ultimately, more oxygen vacancies are formed by the unsaturated Sn and Ti atoms, which benefits electron capture and the redox reaction of adsorbed gases. Thus, the concept of increased unsaturated metal atoms and oxygen vacancy resulting from the doping of different metal ions into each other's lattice has deepened the understanding of gas sensing and the catalytic reaction mechanisms. The lattice synergy of different metals provides a pathway for the design of advanced gas-sensing materials and catalysts.

Imaging Assessment of the Efficacy of Chemotherapy in Primary Malignant Bone Tumors: Recent Advances in Qualitative and Quantitative Magnetic Resonance Imaging and Radiomics.

Recent studies have shown that MRI demonstrates promising results for evaluating the chemotherapy efficacy in bone sarcomas. This article reviews current methods for evaluating the efficacy of malignant bone tumors and the application of MRI in this area, and emphasizes the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Correlation of Intravoxel Incoherent Motion and Diffusion Kurtosis MR Imaging Models With Reactive Stromal Grade in Prostate Cancer.

BACKGROUND: Reactive stroma is recognized as one of the independent prognostic factors in prostate cancer (PCa). Intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) may be useful for assessing the reactive stromal grade (RSG). PURPOSE: To investigate whether IVIM and DKI models can evaluate RSG in PCa patients. STUDY TYPE: Retrospective. SUBJECTS: A total of 56 PCa patients aged 73 years on average confirmed by MRI and transrectal ultrasound (MRI/TRUS) fusion biopsy divided into two subgroups (18 high RSG and 38 low RSG). FIELD STRENGTH/SEQUENCE: A 3 T/T1 WI-fs, T1 WI, T2 WI-fs, T2 WI, DWI, IVIM, and DKI. ASSESSMENT: Apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean diffusion (MD), mean kurtosis (MK) were obtained. Patients were divided into high RSG PCa (>50% reactive stroma) and low RSG PCa (≤50% reactive stroma) groups on hematoxylin and eosin (H&E) stained sections. STATISTICAL TESTS: Spearman correlation and independent sample t-test or Wilcoxon's rank sum test was used to investigate the relationship between each imaging parameter and RSG. The combined parameters were calculated using a binary logistic regression model. Receiver operating characteristic (ROC) analysis was used to explore the value of individual and combined parameters to differentiate between high and low RSG group. Area under the ROC curves (AUC) > 0.7 were used as reference standards. RESULTS: ADC, D, f, and MD values showed positive correlation with RSG (r = 0.489, 0.619, 0.318, and 0.544, respectively); MK showed negative correlation with RSG (r = -0.444). ADC, D, f, and MD values were significantly lower in the low RSG group than in the high RSG group. The combined model showed the best diagnostic ability to differentiate low and high RSG groups (AUC = 0.887). DATA CONCLUSION: Parameters of IVIM and DKI may be promising methods for assessment of RSG in PCa patients. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Intratumoral Heterogeneity of Fibrosarcoma Xenograft Models: Whole-Tumor Histogram Analysis of DWI and IVIM.

RATIONAL AND OBJECTIVE: To explore the correlations of histogram parameters from diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with the heterogeneous features in a nude mouse model of fibrosarcoma. MATERIALS AND METHODS: A total of 44 fibrosarcoma xenograft models were established by inoculating HT-1080 cells on the right thigh of mice and subjected tumors to DWI and IVIM imaging with 3.0 T MRI. Whole-tumor histogram parameters were calculated on apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Heterogeneous features, including necrosis rate, cell density, Ki-67 labeling index (LI), and microvascular density (MVD) were measured. Intraclass correlation coefficients (ICC), Pearson or Spearman correlation tests, and receiver operating characteristics (ROC) were performed. RESULTS: The 90th percentile, skewness and kurtosis of ADC and D histograms showed correlations with necrosis rate, and the highest correlation coefficient was found for D90th (r = 0.485). ADC and D histogram parameters showed correlations with cell density and Ki-67 LI; D90th showed the highest correlation coefficient with cell density (r = -0.504); and Dmedian showed the most significant correlation with Ki-67 LI (r = -0.525). D*skewness, D*kurtosis, D*90th, fmean, and fmedian showed correlations with MVD. ADC90th, ADCskewness, ADCkurtosis, D90th, and Dskewness showed significant differences between the low necrosis and high necrosis groups, and the combination model showed the best diagnostic ability (AUC = 0.882), with 97% sensitivity, and 72.7% specificity. CONCLUSION: Whole-tumor histogram parameters of DWI and IVIM were correlated with heterogeneous features in nude murine models of fibrosarcoma.

Correlation of Apparent Diffusion Coefficient With Proliferation and Apoptotic Indexes in a Murine Model of Fibrosarcoma: Comparison of Four Methods for MRI Region of Interest Positioning.

BACKGROUND: Diffusion-weighted imaging (DWI) has demonstrated great potential in predicting the expression of tumor cell proliferation and apoptosis indexes. PURPOSE: To evaluate the impact of four region of interest (ROI) methods on interobserver variability and apparent diffusion coefficient (ADC) values and to examine the correlation of ADC values with Ki-67, Bcl-2, and P53 labeling indexes (LIs) in a murine model of fibrosarcoma. STUDY TYPE: Prospective, animal model. ANIMAL MODEL: A total of 22 female BALB/c mice bearing intramuscular fibrosarcoma xenografts. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted fast spin-echo (FSE), T2-weighted fast relaxation fast spin-echo, and DWI PROPELLER FSE sequences. ASSESSMENT: Four radiologists measured ADC values using four ROI methods (oval, freehand, small-sample, and whole-volume). Immunohistochemical assessment of Ki-67, Bcl-2, and P53 LIs was performed. STATISTICAL TESTS: Interclass correlation coefficient (ICC), one-way analysis of variance followed by LSD-t post hoc analysis, and Pearson correlation test were performed. The statistical threshold was defined as a P-value of <0.05. RESULTS: All ROI methods for ADC measurements showed excellent interobserver agreement (ICC range, 0.832-0.986). The ADC values demonstrated significant differences among the four ROI methods. The ADC values for oval, freehand, small-sample, and whole-volume ROI methods showed a moderately negative correlation with Ki-67 (r = -0.623; r = -0.629; r = -0.642, and r = -0.431) and Bcl-2 (r = -0.590; r = -0.597; r = -0.659, and r = -0.425) LIs, but no correlation with P53 LI (r = 0.364, P = 0.104; r = 0.350, P = 0.120; r = 0.379, P = 0.091; r = 0.390, P = 0.080). DATA CONCLUSION: The ADC value can be used to evaluate cell proliferation and apoptosis indexes in a murine model of fibrosarcoma, employing the small-sample ROI as a reliable method. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Advances in The Application and Research of Magnetic Resonance Diffusion Kurtosis Imaging in The Musculoskeletal System.

Magnetic resonance diffusion kurtosis imaging (DKI) is an emerging magnetic resonance imaging (MRI) technique that can reflect microstructural changes in tissue through non-Gaussian diffusion of water molecules. Compared to traditional diffusion weighted imaging (DWI), the DKI model has shown greater sensitivity for diagnosis of musculoskeletal diseases and can help formulate more reasonable treatment plans. Moreover, DKI is an important auxiliary examination for evaluation of the motor function of the musculoskeletal system. This article briefly introduces the basic principles of DKI and reviews the application and research of DKI in the evaluation of disorders of the musculoskeletal system (including bone tumors, soft tissue tumors, spinal lesions, chronic musculoskeletal diseases, musculoskeletal trauma, and developmental disorders) as well as the normal musculoskeletal tissues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: 1.

Remission from the 5-Fu-Based Chemotherapy to Gemcitabine-Based Chemotherapy-Based on the Pathological Classification of Periampullary Carcinoma: A Case Report and Literature Review.

Background: Periampullary carcinoma, which includes ampullary carcinoma, pancreatic head cancer, distal common bile duct cancer, and duodenal papillary cancer, is a relatively rare malignancy with uncertain therapeutic options. Although several studies have investigated the efficacy of multiple adjuvant chemotherapy regimens for periampullary carcinoma treatment, the optimal regimen remains to be determined. The inherent heterogeneity of the mucosal origin divides periampullary carcinoma into intestinal and pancreaticobiliary types. Therefore, the selection of chemotherapy regimens based on pathological type may have potential therapeutic significance. Case Presentation: A 72-year-old woman with moderately differentiated periampullary adenocarcinoma experienced disease progression after receiving FOLFOX regimen. Subsequently, the sample was subtyped first by H&E evaluation and then by the evaluation of an IHC panel composed of CK20, CDX2, MUC1, MUC2, and MUC5AC. The pathologists concluded that the patient's sample was of the pancreaticobiliary (PB) subtype. The subsequent change to gemcitabine plus S-1 adjuvant therapy achieved remission of liver metastases based on the pathological classification of the cancer. Conclusion: Based on the pathological classification, adjuvant chemotherapy with gemcitabine may be beneficial for patients with PB subtype periampullary carcinoma. 5-Fu-based adjuvant chemotherapy may be beneficial for patients with intestinal subtype periampullary carcinoma.

Defects of endoscopic biopsy in the diagnosis of periampullary carcinoma and recommendations for diagnosis and treatment: a retrospective study before and after surgery.

Background: Pancreaticoduodenectomy (PD) is the main curative treatment for periampullary carcinoma (PAC), but the high risk of complications in PD means an accurate preoperative diagnosis is essential, because benign lesions can be treated without PD. Despite as the preferred diagnosis method, preoperative endoscopic biopsy is characterized with high false-negative rate, which disturbs the making of surgical plans. We explored the degree of matching between preoperative and postoperative pathological diagnoses, analyzed the shortcomings of endoscopic biopsy, and provide recommendations for the diagnosis and treatment of periampullary tumors. Methods: We retrospectively analyzed 198 patients with periampullary tumors who underwent endoscopic biopsy and PD between June 2013 and February 2021. Data on disease characteristics, such as sex, age, total bilirubin (TBIL), direct bilirubin (DBIL), tumor markers, imaging features, preoperative and postoperative pathology were collected and reviewed. The measurement data with normal distribution were expressed by mean ± standard deviation, and the categorical data were expressed by the number of cases. Results: In our cohort, 196 patients (98.99%) were diagnosed with PAC based on postoperative pathology. Preoperative pathological biopsy was performed in 198 patients with dysplasia (n=76), inflammation (n=7), and PAC (n=115), among whom 111 were diagnosed with PAC at the first biopsy and 4/7 at the second biopsy. The false-negative rate for one preoperative biopsy was 85/196 (43.37%); 74/76 (97.37%) patients in the dysplasia subgroup and 7/7 (100%) patients in the inflammation subgroup showed malignant results after surgery. Conclusions: Preoperative endoscopic biopsy has a high false-negative rate. Multiple sites, greater depth, and more biopsies may increase accuracy. Patients preoperatively diagnosed with dysplasia have a high risk for cancer and are recommended to undergo PD directly.

α2-macroglobulin-rich serum as a master inhibitor of inflammatory factors attenuates cartilage degeneration in a mini pig model of osteoarthritis induced by "idealized" anterior cruciate ligament reconstruction.

Post-traumatic osteoarthritis is a special type of osteoarthritis and a common disease, with few effective treatments available. α2-Macroglobulin (α2M) is important to chondral protection in post-traumatic osteoarthritis. However, its injection into xenogeneic joint cavities involves safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat post-traumatic osteoarthritis has significant value. In the present study, a unique filtration process was used to obtain α2MRS from human and mini pig serum. We evaluated the potential of α2MRS in protecting against post-surgery cartilage degeneration. We identify the potential of α2MRS in reducing the expression of inflammatory cytokines and factors that hasten cartilage degeneration in post-operative conditions leading to post-traumatic osteoarthritis. The potential of α2MRS was analyzed in interleukin-1ß induced human chondrocytes and mini pig models. In the chondrocyte model, α2MRS significantly promoted human chondrocyte proliferation and reduced apoptosis and chondrocyte catabolic cytokine gene transcription and secretion. The anterior cruciate ligament autograft reconstruction model of mini pigs was randomized into groups, operated on, and injected with α2MRS or saline. The results showed that α2MRS injection significantly suppressed the levels of inflammatory factors, improved gait, and showed significantly lower cartilage degeneration than the groups that did not receive α2MRS injections. This study highlights the chondroprotective effects of α2MRS, elucidated its potential applications against cartilage degeneration, and could provide a basis for the clinical translation of α2MRS.

One-Step Synthesis of Nitrogen/Fluorine Co-Doped Carbon Dots for Use in Ferric Ions and Ascorbic Acid Detection.

Carbon dots (CDs) have caught enormous attention owing to their distinctive properties, such as their high water solubility, tunable optical properties, and easy surface modification, which can be generally used for the detection of heavy metals and organic pollutants. Herein, nitrogen and fluorine co-doped carbon dots (NFCDs) were designed via a rapid, low-cost, and one-step microwave-assisted technique using DL-malic acid and levofloxacin. The NFCDs emitted intense green fluorescence under UV lighting, and the optical emission peak at 490 nm was observed upon a 280 nm excitation, with a high quantum yield of 21.03%. Interestingly, the spectral measurements illustrated excitation-independent and concentration-independent single-color fluorescence owing to the presence of nitrogen and fluorine elements in the surface functional groups. Additionally, the NFCDs were applied for the selective detection of Fe3+ and ascorbic acid based on the "turn-off" mode. The detection limits were determined as 1.03 and 4.22 µM, respectively. The quenching mechanisms were explored using the static quenching mechanism and the inner filter effect. Therefore, a NFCDs fluorescent probe with single color emission was successfully developed for the convenient and rapid detection of Fe3+ and ascorbic acid in environments.

Adjuvant therapy for periampullary carcinoma and the significance of histopathological typing: A systematic review.

OBJECTIVE: This review investigates the role of adjuvant therapy (AT) and the importance of histopathological typing in periampullary carcinoma (PAC) treatment. BACKGROUND: PAC is a relatively rare gastrointestinal malignancy. The regimen and effect of AT in PAC are still controversial. However, there is a treatment based on histopathological types (pancreaticobiliary-type, PB-type or intestinal-type, IN-type), but there are no clear guidelines indicating that typing can be used to guide the selection of AT drugs. METHODS: A literature search of PubMed and Web of Science databases was conducted for studies published from January 2001 to August 2021 on the use of AT in PAC. RESULTS: A total of 75 studies were included in this review. According to existing studies, AT for PAC is mostly based on 5-FU or gemcitabine, but the effect is unknown. However, when PAC is classified into different histopathological types, AT with gemcitabine is beneficial for patients with the PB-type of PAC, while 5-FU-based AT is beneficial for patients with the IN-type of PAC. In addition, the benefits of AT are more pronounced in patients with a high-risk disease, such as patients with stage II/III, T3/T4 tumors, or positive lymph node involvement. There are few studies on targeted therapy and immunotherapy for PAC. CONCLUSIONS: This review suggests that AT has potential survival benefits, especially when based on the histopathologic type that helps the choice of drugs during AT in PAC patients.

Improving the symptoms of post-traumatic osteoarthritis by α2-macroglobulin-rich serum.

PURPOSE: Altered joint loading by trauma induces joint degeneration, eventually leading to the generation of post-traumatic osteoarthritis (PTOA). Recent studies have shown that α2-macroglobulin (A2M) inhibits PTOA, induced by anterior cruciate ligament transection (ACLT), pathogenesis by regulating proinflammatory cytokines and matrix metalloproteinases. However, the application of A2M is limited due to high prices. Therefore, the aim of this study is to explore the novel preparation of A2M. MATERIALS AND METHODS: The early change of A2M in synovial fluid and serum was measured by ELISA. Ultra-filtered centrifugation was performed to prepare α2-macroglobulin-rich serum (A2MRS). The bioactivity of A2M in A2MRS was detected by improved Ellis and Gollas-Galvan method. The effects of A2MRS on PTOA were observed using immunohistochemistry, safranine O staining, micro X-ray, fluorescence molecular tomography etc. RESULTS: The concentration of A2M in PTOA group was significantly higher than that in Sham group in synovial fluid on the third day after ACLT in rat PTOA model. On the contrary, a significant downregulation of A2M levels in PTOA group was observed compared to the Sham group in serum at the seventh day after ACLT. Secondly, A2MRS was prepared successfully, and the concentration and bioactivity of A2M in A2MRS was significantly higher than that in serum. Lastly, A2MRS not only reduced notably the production of secondary cartilage ossification, type 10 collagen and matrix metalloproteinase 13, but also increased profoundly the generation of type 2 collagen, aggrecan, and chondrocytes' number. CONCLUSION: Our results indicate that A2MRS has protective effects on PTOA.

Increasing the bioactivity of kynurenine by ultraviolet irradiation via resonance energy transfer in vitro.

Kynurenine (Kyn) is involved in a variety of physiological/pathological reactions via activating aryl hydrocarbon receptor (Ahr). However, how to activate Ahr by Kyn under physiological/pathological conditions is still unclear. Here, we presented that Kyn (8 µM, a concentration less than the dose of Kyn-induced Ahr activation) significantly induced the nuclear transfer of Ahr and the expression of cytochrome P450 1A1 (CYP1A1, a classic biomarker for Ahr activation) when co-administered with ultraviolet (UV) irradiation in 95D cells, which were transfected transiently with siRNA against indoleamine 2,3-dioxygenase 1 (IDO 1) and cultured in cell medium supplemented with bovine serum containing bovine serum albumin (BSA), in vitro. Additionally, we found that the fluorescence intensity of BSA was attenuated by Kyn (2, 4, 6, 8, 10, 12 and 14 µM) mainly through quenching the fluorescence of tryptophan (Trp) residues in the pattern of dynamic quenching related to molecular diffusion. More important, resonance energy transfer from excited-state BSA to Kyn was confirmed, leading to the generation "energetic" Kyn that might be ability of hyperactivity according to the theory of photochemical reaction. These data indicate that UV irradiation is contributable for Kyn to function, and present a novel pattern of altering the activity of biomolecules to some degree.

Decreased Expression of Programmed Death Ligand-L1 by Seven in Absentia Homolog 2 in Cholangiocarcinoma Enhances T-Cell-Mediated Antitumor Activity.

N6-methyladenosine (m6A) has been reported as an important mechanism of post-transcriptional regulation. Programmed death ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. In addition, seven in absentia homolog 2 (Siah2), a RING E3 ubiquitin ligase, has been involved in tumorigenesis and cancer progression. However, the role of m6A-METTL14-Siah2-PD-L1 axis in immunotherapy remains to be elucidated. In this study, we showed that METTL14, a component of the m6A methyltransferase complex, induced Siah2 expression in cholangiocarcinoma (CCA). METTL14 was shown to enrich m6A modifications in the 3'UTR region of the Siah2 mRNA, thereby promoting its degradation in an YTHDF2-dependent manner. Furthermore, co-immunoprecipitation experiments demonstrated that Siah2 interacted with PD-L1 by promoting its K63-linked ubiquitination. We also observed that in vitro and in vivo Siah2 knockdown inhibited T cells expansion and cytotoxicity by sustaining tumor cell PD-L1 expression. The METTL14-Siah2-PD-L1-regulating axis was further confirmed in human CCA specimens. Analysis of specimens from patients receiving anti-PD1 immunotherapy suggested that tumors with low Siah2 levels were more sensitive to anti-PD1 immunotherapy. Taken together, our results evidenced a new regulatory mechanism of Siah2 by METTL14-induced mRNA epigenetic modification and the potential role of Siah2 in cancer immunotherapy.

An Update in Imaging Evaluation of Histopathological Grade of Soft Tissue Sarcomas Using Structural and Quantitative Imaging and Radiomics.

Over the past two decades, considerable efforts have been made to develop non-invasive methods for determining tumor grade or surrogates for predicting the biological behavior, aiding early treatment decisions, and providing prognostic information. The development of new imaging tools, such as diffusion-weighted imaging, diffusion kurtosis imaging, perfusion imaging, and magnetic resonance spectroscopy have provided leverage in the diagnosis of soft tissue sarcomas. Artificial intelligence is a new technology used to study and simulate human thinking and abilities, which can extract and analyze advanced and quantitative image features from medical images with high throughput for an in-depth characterization of the spatial heterogeneity of tumor tissues. This article reviews the current imaging modalities used to predict the histopathological grade of soft tissue sarcomas and highlights the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Impaired bone healing by enoxaparin via inhibiting the differentiation of bone marrow mesenchymal stem cells towards osteoblasts.

INTRODUCTION: Enoxaparin is widely used to prevent venous thromboembolism after orthopedic surgery and has some adverse effects, such as osteoporosis and delay in fracture healing. However, the exact mechanism delaying bone healing by enoxaparin is still unclear. MATERIALS AND METHODS: X-ray and Micro-CT scanning were performed to detect the effects of enoxaparin on bone healing at rat model of bone defeat. CCK-8 assay and flow cytometry were conducted to measure the effects of enoxaparin on bone marrow mesenchymal stem cells (BMSCs). The mRNA/protein levels of osteocalcin (OCN), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2) were analyzed by real-time PCR and western blotting, respectively. Alizarin red staining was used to observe the mineralized nodules. RESULTS: Enoxaparin (2000 AXaIU/kg) not only profoundly increased the trabecular separation, but also notably decreased the trabecular bone volume/tissue volume, trabecular thickness, trabecular number and OCN level, in vivo. Additionally, significantly inhibiting proliferation of BMSCs by enoxaparin (1.0 and 10 AXaIU/ml) was detected. The apoptosis and the ratio of G phase cells in enoxaparin (0.1, 1.0 and 10 AXaIU/ml) group were obviously higher than that in control group. While the ratio of S phase cells was downregulated markedly by enoxaparin (0.1,1.0 and 10 AXaIU/ml) compared with the control group. Most importantly, inducing significant decreases of OCN/Runx2 mRNA/protein expression and formation of mineralized nodules by enoxaparin (0.1, 1.0 and 10 AXaIU/ml) were observed compared with the control group. While the notable decreases of BMP2 mRNA/protein level were only detected in enoxaparin (10 AXaIU/ml) group. CONCLUSION: It was suggested that enoxaparin impaired bone healing through suppressing the differentiation of BMSCs towards osteoblasts.

Corrigendum: Decreased expression of programmed death ligand-L1 by seven in absentia homolog 2 in cholangiocarcinoma enhances T-cell-mediated antitumor activity.

[This corrects the article DOI: 10.3389/fimmu.2022.845193.].

Laparoscopic transcystic common bile duct exploration in patients with a nondilated common bile duct.

BACKGROUND: Laparoscopic transcystic common bile duct exploration (LTCBDE) is the minimally traumatic surgical method for the treatment of choledocholithiasis secondary to cholecystolithiasis with dilated common bile duct (CBD). However, no report exists concerning LTCBDE in patients with nondilated CBD. The purpose of this study was thus to explore the safety, efficacy, and feasibility of LTCBDE in patients with choledocholithiasis secondary to cholecystolithiasis with nondilatation of the CBD. METHODS: We retrospectively analyzed 47 patients with choledocholithiasis secondary to cholecystolithiasis who were treated with LTCBDE at the Second Affiliated Hospital of Nanchang University from January 2017 to August 2021 (all the patients had undergone endoscopic retrograde cholangio-pancreatography treatment, but this failed due to various reasons). Clinical data on disease characteristics, methods for cystic duct incision and CBD stone extraction, and surgical outcomes were collected and reviewed. Each patient was followed up for more than 3 months. RESULTS: There were 47 patients in this study, including 21 females and 26 males, with their ages ranging from 15 to 82 years (51±15 years). All patients were treated with surgery, and the CBD stones were removed successfully. Among these patients, 45 underwent LTCBDE for the removal of stones in the CBD, with failure occurring in 2 patients who then accepted laparoscopic common bile duct stone removal (LCBDE) + T tube drainage. The diameter of the cystic duct was 0.30-0.73 cm (0.60±0.07 cm), the diameter of the CBD was 0.60-0.80 cm (0.73±0.05 cm), the operation time was 75-220 minutes (159±33 minutes), and the postoperative hospital stay was 2-13 days (6±2 days). None of the patients experience any serious postoperative complications, and all were discharged safely. During the follow-up, no postoperative biliary stenosis, bile leakage, or other complications occurred. CONCLUSIONS: LTCBDE is feasible to treat patients with choledocholithiasis secondary to cholecystolithiasis with nondilatation of the CBD. This choice of treatment plan reduces the length of hospital stay and the occurrence of postoperative complications. However, it is recommended that this be attempted on the basis of the experience of LTCBDE with dilated CBD.

Autografts vs Synthetics for Cruciate Ligament Reconstruction: A Systematic Review and Meta-Analysis.

To describe the outcomes of autografts and synthetics in anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction with respect to instrumented laxity measurements, patient-reported outcome scores, complications, and graft failure risk. We searched PubMed, Cochrane Library, and EMBASE for published randomized controlled trials (RCT) and case controlled trials (CCTs) to compare the outcomes of the autografts versus synthetics after cruciate ligament reconstruction. Data analyses were performed using Cochrane Collaboration RevMan 5.0. Nine studies were identified from the literature review. Of these studies, three studies compared the results of bone-patellar tendon-bone (BPTB) and ligament augmentation and reconstruction system (LARS), while six studies compared the results of four-strand hamstring tendon graft (4SHG) and LARS. The comparative study showed no difference in Lysholm score and failure risk between autografts and synthetics. The combined results of the meta-analysis indicated that there was a significantly lower rate of side-to-side difference > 3 mm (Odds Ratio [OR] 2.46, 95% confidence intervals [CI] 1.44-4.22, P = 0.001), overall IKDC (OR 0.40, 95% CI 0.19-0.83, P = 0.01), complications (OR 2.54, 95% CI 1.26-5.14, P = 0.009), and Tegner score (OR -0.31, 95% CI -0.52-0.10, P = 0.004) in the synthetics group than in the autografts group. This systematic review comparing long-term outcomes after cruciate ligament reconstruction with either autograft or synthetics suggests no significant differences in failure risk. Autografts were inferior to synthetics with respect to restoring knee joint stability and patient-reported outcome scores, and were also associated with more postoperative complications.