Causal effects of osteoporosis on structural changes in specific brain regions: a Mendelian randomization study.

Observational studies have reported that osteoporosis is associated with cortical changes in the brain. However, the inherent limitations of observational studies pose challenges in eliminating confounding factors and establishing causal relationships. And previous observational studies have not reported changes in specific brain regions. By employing Mendelian randomization, we have been able to infer a causal relationship between osteoporosis and a reduction in the surficial area (SA) of the brain cortical. This effect is partially mediated by vascular calcification. We found that osteoporosis significantly decreased the SA of global brain cortical (ß = -1587.62 mm2, 95%CI: -2645.94 mm2 to -529.32 mm2, P = 0.003) as well as the paracentral gyrus without global weighted (ß = - 19.42 mm2, 95%CI: -28.90 mm2 to -9.95 mm2, P = 5.85 × 10-5). Furthermore, we estimated that 42.25% and 47.21% of the aforementioned effects are mediated through vascular calcification, respectively. Osteoporosis leads to a reduction in the SA of the brain cortical, suggesting the presence of the bone-brain axis. Vascular calcification plays a role in mediating this process to a certain extent. These findings establish a theoretical foundation for further investigations into the intricate interplay between bone, blood vessels, and the brain.

Targeted strategies to deliver boron agents across the blood-brain barrier for neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT), as an innovative radiotherapy technology, has demonstrated remarkable outcomes when compared to conventional treatments in the management of recurrent and refractory brain tumors. However, in BNCT of brain tumors, the blood-brain barrier is a main stumbling block for restricting the transport of boron drugs to brain tumors, while the tumor targeting and retention of boron drugs also affect the BNCT effect. This review focuses on the recent development of strategies for delivering boron drugs crossing the blood-brain barrier and targeting brain tumors, providing new insights for the development of efficient boron drugs for the treatment of brain tumors.

Risk of osteoporosis in patients treated with direct oral anticoagulants vs. warfarin: an analysis of observational studies.

Aims: Evidence on the association between the risk of new-onset osteoporosis and oral anticoagulants remains controversial. We aimed to compare the risk of osteoporosis associated with the use of direct oral anticoagulants (DOACs) with that associated with warfarin use. Methods: Studies published up to 15 March 2023 that investigated the association between the use of DOACs and warfarin and the incidence of osteoporosis were identified by online searches in PubMed, Embase, the Cochrane Library, and Web of Science conducted by two independent investigators. Random-effects or fixed-effect models were employed to synthesize hazard ratios (HRs)/relative ratios (RRs) with 95% confidence intervals (CIs) for estimating the risk of osteoporosis correlated with DOAC and warfarin prescriptions (PROSPERO No. CRD42023401199). Results: Our meta-analysis ultimately included four studies involving 74,338 patients. The results suggested that DOAC use was associated with a significantly lower incidence of new-onset osteoporosis than warfarin use (pooled HR: 0.71, 95% CI: 0.57 to 0.88, p < 0.001, I 2: 85.1%). Subanalyses revealed that rivaroxaban was associated with a lower risk of osteoporosis than both warfarin and dabigatran. In addition, DOACs were associated with a lower risk of developing osteoporosis than warfarin in both male and female patients, in patients with atrial fibrillation (AF), and in patients who underwent therapy for > 365 days. Conclusion: DOAC users experienced a lower incidence of osteoporosis than warfarin users. This study may give us insight into safe anticoagulation strategies for patients who are at high risk of developing osteoporosis. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023401199.

Genetically Engineered Artificial Exosome-Constructed Hydrogel for Ovarian Cancer Therapy.

Owing to the insidious onset of ovarian cancer, most patients are in the advanced stage with extensive peritoneal metastasis when they are diagnosed. Treatment of peritoneal metastasis from advanced ovarian cancer remains a significant challenge. Inspired by the massive macrophages in the peritoneal environment, here, we reported an artificial exosome-based peritoneal-localized hydrogel to domesticate peritoneal macrophages as the therapeutic target for realizing potent ovarian cancer therapy, where artificial exosomes derived from genetically sialic-acid-binding Ig-like lectin 10 (Siglec-10)-engineered M1-type macrophages were chemically designed as gelator. Upon triggering immunogenicity with X-ray radiation, our hydrogel encapsulating efferocytosis inhibitor MRX-2843 enabled a cascade regulation to orchestrate polarization, efferocytosis, and phagocytosis of peritoneal macrophages for realizing robust phagocytosis of tumor cells and powerful antigen presentation, offering a potent approach for ovarian cancer therapy via bridging the innate effector function of macrophages with their adaptive immune response. Moreover, our hydrogel is also applicable for potent treatment of inherent CD24-overexpressed triple-negative breast cancer, providing an emerging therapeutic regimen for the most lethal malignancies in women.

Altered glutamate-glutamine and amide proton transfer-weighted values in the hippocampus of patients with amnestic mild cognitive impairment: A novel combined imaging diagnostic marker.

Background and purpose: Early diagnosis of amnestic mild cognitive impairment (aMCI) and timely management to delay the onset of Alzheimer's disease (AD) would benefit patients. Pathological metabolic changes of excitatory/inhibitory neurotransmitters and abnormal protein deposition in the hippocampus of aMCI may provide a new clue to imaging diagnosis. However, the diagnostic performance using these hippocampal metabolite measurements is still unclear. We aimed to quantify right hippocampal glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) levels as well as protein-based amide proton transfer-weighted (APTw) signals of patients with aMCI and investigate the diagnostic performance of these metabolites. Methods: In this cross-sectional study, 20 patients with aMCI and 20 age- and gender-matched healthy controls (HCs) underwent MEGA Point Resolved Spectroscopy (MEGA-PRESS) and APTw MR imaging at 3 T. GABA+, Glx, and APTw signals were measured in the right hippocampus. The GABA+ levels, Glx levels, Glx/GABA+ ratios, and APTw values were compared between the HCs and aMCI groups using the Mann-Whitney U test. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate MEGA-PRESS and APTw parameters' diagnostic performance. Results: Compared with HCs, patients with aMCI had significantly lower Glx levels in the right hippocampus (7.02 ± 1.41 i.u. vs. 5.81 ± 1.33 i.u., P = 0.018). No significant changes in the GABA+ levels were observed in patients with aMCI (HCs vs. aMCI: 2.54 ± 0.28 i.u. vs. 2.47 ± 0.36 i.u., P = 0.620). In addition, Glx/GABA+ ratios between the two groups (HCs vs. aMCI: 2.79 ± 0.60 vs. 2.37 ± 0.55, P = 0.035) were significantly different. Compared with HCs, patients with aMCI showed higher APTw values in the right hippocampus (0.99 ± 0.26% vs. 1.26% ± 0.28, P = 0.006). The ROC curve analysis showed that Glx, GABA+, Glx/GABA+, and APTw values had an area under the curve (AUC) of 0.72, 0.55, 0.70, and 0.75, respectively, for diagnosing aMCI. In the ROC curve analysis, the AUC of the combination of the parameters increased to 0.88, which is much higher than that observed in the univariate analysis (P < 0.05). Conclusion: The combination of right hippocampal Glx levels and APTw values improved the diagnostic performance for aMCI, indicating it as a promising combined imaging diagnostic marker. Our study provided a potential imaging diagnostic strategy of aMCI, which may promote early detection of aMCI and facilitate timely intervention to delay the pathological progress toward AD.

Radiotherapy-mediated redox homeostasis-controllable nanomedicine for enhanced ferroptosis sensitivity in tumor therapy.

Ferroptosis has received increasing attentions in cancer therapy owing to its unique advantages over apoptosis. However, ferroptosis is governed by the efficiency of reactive oxygen species (ROS) production and the tumor cell antioxidant microenvironment that compromises therapeutic efficacy of ferroptosis. It is of great significance to develop a strategy that can both achieve high-efficiency ROS production and modulate tumor cell antioxidant microenvironment to amplify ferroptosis. However, until now, such a strategy has rarely been realized. Here, we, for the first time, reported a radiotherapy -mediated redox homeostasis-controllable nanomedicine for amplifying ferroptosis sensitivity in tumor therapy. The nanomedicine is constructed by co-assembling a ferroptosis inducer hemin and a thioredoxin 1 (Trx-1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) with human serum albumin. For our nanomedicine, hemin converts H2O2 to ROS via Fenton reaction to induce ferroptosis while PX-12 effectively inhibits the activity of antioxidant Trx-1 to suppress ROS depletion, resulting in amplified ferroptosis. Particularly, combining radiotherapy with the nanomedicine, radiotherapy depletes the other key antioxidant glutathione and generates additional radiotherapy-induced ROS, further boosting the ferroptosis effect. Therefore, our strategy can simultaneously ensure efficient ROS production and regulation of tumor cell antioxidant microenvironment, thereby enhancing efficacy of ferroptosis in tumor therapy. Our work offers an innovative approach to amplify ferroptosis sensitivity against tumors by simultaneously promoting ROS production and regulating redox homeostasis. STATEMENT OF SIGNIFICANCE: The antioxidants such as thioredoxin 1 (Trx-1) and glutathione (GSH) in tumor cells, are significantly upregulated by the innate cancer cellular redox homeostasis, severely restricting the reactive oxygen species (ROS)-based therapy and compromising the effect of Fenton reaction-induced ferroptosis against tumors. It is urgent to develop a strategy to simultaneously achieve Fenton reaction-induced ferroptosis and regulate the cancer cellular redox homeostasis against upregulated levels of Trx-1 and GSH. A radiotherapy-mediated redox homeostasis-regulatable nanomedicine was designed for amplifying ferroptosis sensitivity in tumor therapy, where the therapeutic efficacy of ferroptosis against tumors can be significantly amplified by integrating Fenton reaction-induced and radiotherapy-induced ferroptosis as well as PX-12-enabled inhibition of antioxidant Trx-1 and radiotherapy-induced downregulation of antioxidant GSH levels.

The efficacy and safety of Apatinib in the treatment of advanced non-small cell lung cancer: A retrospective trial.

Background: As a potent inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway, Apatinib has been used in antitumor treatment for some time. The study aimed to research the therapeutic effects and toxicity of Apatinib in the treatment of advanced non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed 128 NSCLC patients treated with Apatinib in Qilu Hospital of Shandong University. Response Evaluation Criteria in Solid Tumors (RECIST) criteria was adopted to evaluate the treatment effect, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was conducted to determine the Adverse Events (AEs). Cox proportional hazard model and Kaplan-Meier function were applied to evaluate the progression-free survival (PFS) and overall survival (OS). Results: Among 128 NSCLC patients, partial response (PR) were observed in 15 patients, stable disease (SD) in 66 patients and progressive disease (PD) in 47 patients. The objective response rate (ORR) and disease control rate (DCR) accounted for 11.7% and 63.3% respectively. The median PFS (mPFS) and median OS (mOS) were 4.4 months and 17.2 months. Common side effects of Apatinib were hypertension (n=48), proteinuria (n=35), and hand-foot syndrome (HFS) (n=30), all of the side effects were controllable. No significant difference was observed in efficacy and AEs between the higher dose group (Apatinib>500mg/d) and the lower dose group (Apatinib=500mg/d). Conclusions: The study suggested that Apatinib with a lower dose (=500mg/d) has good efficacy and safety in the treatment of advanced NSCLC after first-line chemotherapy.

Treatment of Scoliosis with One-Stage Posterior Pedicle Screw System by Paraspinal Intermuscular Approach: A Minimum of Two Years of Follow-Up.

OBJECTIVE: To evaluate the clinical efficacy of the treatment of scoliosis with a pedicle screw system through paraspinal intermuscular approach (PIA). METHODS: This is a retrospective case series study. A total of 10 patients diagnosed with scoliosis had surgical indications and treated with a pedicle screw system in one-stage posterior surgery by PIA from March 2013 to April 2015 at the First Hospital of Jilin University were enrolled in this study. The average age of the patients was 14.9 years, including one male and nine females. The operative information and surgical results, including Cobb angle correction, correction loss, global balance (including Frontal Plane Balance [FPB] and Sagittal Plane Balance [SPB]), and fusion rate were reviewed. Functional outcomes including visual analog scale (VAS) back pain score, leg pain score, and Scoliosis Research Society-22 questionnaire (SRS-22) were used to evaluate the quality of life of patients preoperatively and at last follow-up. RESULTS: Each patient was followed up at least six times. The average follow-up time was 43.2 months. Mean scoliosis and kyphosis improved from 68.5° ± 18.1°to 18.7° ± 11.8° and from 34.4° ± 17.9°to 24.0° ± 6.7°, respectively (p < 0.05); at last follow-up, it was 20.1° and 24.7°, respectively (p > 0.05). During the follow-up, mean coronal and sagittal correction loss was 1.4° ± 1.2°and 0.7° ± 0.8°, respectively (p > 0.05). Mean FPB improved from 32.7 to 11.7 mm (p < 0.05); Mean SPB changed from 0.3 to -0.7 mm (p > 0.05). No dural tears were observed during the corrective surgery or wound infection or implant-related complications. No pseudoarthrosis was identified according to the last follow-up three-dimensional (3D) CT scan. All the domains in SRS-22 questionnaire show statistically significant improvement at the last follow-up (p < 0.05). The VAS back pain scores improved from a mean preoperative score of 1.7 to a mean postoperative score of 0.2 (p < 0.05). CONCLUSION: This original one-stage posterior PIA is safe and effective in the treatment of scoliosis, which is characterized with less blood loss, shorter operation time, and satisfactory bony fusion.

Circ0007042 alleviates intervertebral disc degeneration by adsorbing miR-369 to upregulate BMP2 and activate the PI3K/AKt pathway.

BACKGROUND: To identify regulatory ncRNA molecules that can cause differential expression of CDH2 in intervertebral disc degeneration (IDD) and explore whether there are other ways to affect the progression of IDD. METHODS: A primary culture of human nucleus pulposus (NP) cells was established and identified by immunofluorescence. An in vitro IDD model was constructed by compressing human NP cells, and the MTT assay was used to measure cell viability. Changes in the ncRNA group were analysed by RNA-seq. The expression levels of hsa_circ_7042, CDH2, and miR-369-3p were detected by qPCR. Cell apoptosis, senescence, and extracellular matrix (ECM) metabolism were detected by flow cytometry, ß-galactosidase staining, and Western blotting. hsa_circ_7042, miR-369-3p, and bone morphogenetic protein 2 (BMP2) were verified by luciferase and RNA immunoprecipitation (RIP) analyses. The PI3K/Akt pathway was validated by transfection of BMP2 siRNA. Furthermore, a mouse model of lumbar spine instability was constructed. circ_7042 adenovirus was packaged and injected into the intervertebral discs of mice, and the influence of circ_7042 overexpression on intervertebral disc degeneration was determined. RESULTS: Western blotting, qPCR, and flow cytometry analyses confirmed that overexpression of circ_7042 could downregulate miR-369-3p and upregulate the expression of CDH2 and BMP2 in IDD cell and animal models. Additionally, the levels of apoptotic and senescent cells decreased, and ECM degradation decreased. The PI3K/Akt pathway was significantly activated after circ_7042 was overexpressed. The injection of circ_7042-overexpressing adenovirus effectively reduced ECM degradation and the level of apoptosis in NP tissue. CONCLUSIONS: circ_7042 could upregulate the expression of CDH2 and BMP2 by absorbing miR-369-3p, and the increased BMP2 activated the PI3K/Akt pathway, thus improving IDD.

Study of PD-1 Inhibitors in Combination with Chemoradiotherapy/Chemotherapy in Patients with Esophageal Squamous Carcinoma.

In this study, we aimed to evaluate the efficacy of PD-1 inhibitors in combination with concurrent CRT/CT for patients with inoperable ESCC in the real world and to find predictors for the efficacy of PD-1 inhibitors. Patients with unresectable ESCC were evaluated at baseline. The clinical data of patients with ESCC who received CRT/CT with or without PD-1 inhibitor were collected and retrospectively reviewed. The objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) were analyzed statistically. A total of 96 patients with ESCC were included. As compared with a control group (n = 48), the PFS (6.0 months vs. 5.0 months, p = 0.025) and 6-month OS (70.8% vs. 47.9%, p < 0.001) were significantly longer in the ICIs group (n = 48). There were no significant differences in ORR and 12-month OS between the two groups. In addition, we found that body mass index (BMI) was associated with PFS (HR 0.85, 95% CI 0.76−0.95, and p = 0.004) and OS (HR 0.82, 95% CI 0.69−0.98, and p = 0.033) in the ICIs group. PD-1 inhibitors combined with CRT/CT is safe with acceptable complications and improved survival for patients with inoperable ESCC. CRT plus PD-1 inhibitor has superior antitumor efficacy. BMI was positively correlated with the efficacy of PD-1 inhibitors.

Prognostic Significance of Preoperative Prognostic Nutritional Index for Overall Survival and Postoperative Complications in Esophageal Cancer Patients.

BACKGROUND: Prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are the most common factors to estimate nutritional and inflammatory status. The aim of this study is to systematically evaluate the prognostic significance of above nutritional and inflammatory indexes for overall survival (OS) and surgical complications in esophageal cancer patients. METHODS: Esophageal cancer patients who underwent esophagectomy were retrospectively collected. PNI, NLR, PLR, and SII were introduced to evaluate the baseline nutritional and inflammatory status. RESULTS: A total of 407 patients were included in the present study. Kaplan-Meier survival analysis revealed that PNI-low group, NLR-high group and PLR-high group, all showed a significantly shorter OS (34.38% vs 49.46%, P < 0.001; 36.13% vs 48.26%, P = 0.026 and 33.33% vs 48.52%, P = 0.001 respectively), while no significant difference was found in SII groups (42.33% vs 46.31%, P = 0.067). Multivariable analyses identified PNI (P = 0.002) was an independent prognostic factor for OS, but NLR (P = 0.672) and PLR (P = 0.186) were not. Postoperative complications occurred significantly more frequently in the low-PNI group (29.69% vs 13.26%, P < 0.001). However, no significant differences were found in the postoperative complication rates between different NLR (16.67% vs 22.69%, P = 0.124), PLR (18.03% vs 19.61%, P = 0.867) and SII (15.34% vs 20.49%, P = 0.326) groups. Multivariate logistic regression analysis showed only PNI (P = 0.008) was an independent prognostic factor for postoperative complications. CONCLUSION: Preoperative low PNI was not only an independent prognostic factor for worse survival in esophageal cancer patients but also associated with high incidence of postoperative complications.

MicroRNA-140-3p alleviates intervertebral disc degeneration via KLF5/N-cadherin/MDM2/Slug axis.

MicroRNAs (miRNAs) are associated with healing or deteriorating degenerated intervertebral disc (IVD) tissues in spinal cord diseases, including intervertebral disc degeneration (IDD). IDD represents a chronic process of extracellular matrix destruction, but the relevant molecular mechanisms implicated in the regenerative effects of miRNAs are unclear. Here, we investigated the regenerative effects of microRNA-140 (miR-140-3p) in an IDD model induced by annulus needle puncture. Bioinformatics analysis was conducted to identify regulatory factors (KLF5/N-cadherin/MDM2/Slug) linked to miR-140-3p effects in IDD. Mesenchymal stem cells (MSCs) were extracted from degenerated IVD nucleus pulposus (NP), and the expression of miR-140-3p/KLF5/N-cadherin/MDM2/Slug was manipulated to explore their effects on cell proliferation, migration, apoptosis and differentiation. The results showed that miR-140-3p was under-expressed in the degenerated IVD NP, whereas its overexpression alleviated IDD. Mechanistic studies suggested that miR-140-3p targeted KLF5 expression, and high KLF5 expression impeded the migration and differentiation of MSCs. In degenerated IVD NP-derived MSCs, MiR-140-3p-mediated KLF5 downregulation simultaneously elevated N-cadherin expression and transcriptionally inhibited MDM2, thus upregulating Slug expression. The experimental data indicated that miR-140-3p enhanced the proliferation, migration and differentiation of degenerated IVD NP-derived MSCs and repressed their apoptosis. The in vivo validation experiment also demonstrated that miR-140-3p inhibited IDD by modulating the KLF5/N-cadherin/MDM2/Slug axis. Collectively, our results uncovered the regenerative role of miR-140-3p in IDD via regulation of the KLF5/N-cadherin/MDM2/Slug axis, which could be a potential therapeutic target for IDD.Abbreviations: miR-140-3p: microRNA-140-3p; IDD: intervertebral disc degeneration; MSCs: Mesenchymal stem cells; IVD: intervertebral disc; MSCs: mesenchymal stem cells; KLF5: Kruppel-like factor 5; MDM2: mouse double minute 2; NC: negative control; DHI: disc height index.

Dynamic Change of Amide Proton Transfer Imaging in Irradiated Nasopharyngeal Carcinoma and Related Histopathological Mechanism.

OBJECTIVE: To investigate the dynamic change of amide proton transfer (APT) imaging before and after irradiation in nasopharyngeal carcinoma (NPC) and the underlying histopathological mechanism. MATERIALS AND METHODS: Tumor-bearing BALB/C nude mouse models were established and randomly divided into three groups: high-dose group (20 Gy/2 fractions), low-dose group (10 Gy/2 fractions), and control group (0 Gy). MRI scanning was performed before irradiation and 3rd, 6th, and 9th day post-irradiation. Scanning sequence included T1 weighted, T2 weighted, and APT. HE staining and TUNEL immunofluorescence detection were performed to detect necrosis and apoptosis. RESULTS: After high-dose irradiation, the mean tumor APT values decreased significantly on the 3rd day and 6th day (from 3.83 before radiotherapy to 2.41%, P < 0.001, 3rd day; from 2.41 to 1.80%, P = 0.001, 6th day). For low-dose irradiation, the mean tumor APT values decreased slightly on the 3rd day and 6th day (from 3.52 to 3.13%, P = 0.109, 3rd day; from 3.13 to 3.05%, P = 0.64, 6th day). The mean APT values of nonirradiated tumor changed slightly. In contrast, the average volume of high-dose irradiated tumors did not decrease obviously until the 9th day post-irradiation (from 290 before radiotherapy to 208 mm3 on the 9th day). The low-dose irradiated tumors showed slow growth, and the nonirradiated tumors showed rapid growth. Subsequent HE staining and TUNEL staining showed obvious necrosis characteristics and higher proportion of positive apoptotic cell nucleus in high-dose irradiated tumors, but not nonirradiated tumors. CONCLUSION: The APT signal intensity decreased after irradiation, which is earlier than the change of tumor volume. What is more, the decrease of APT signal intensity is more significant in high-dose group. Histological analysis showed obvious apoptosis and necrosis histological characteristic in irradiated tumor, which may explain the decrease of APT signal intensity. These results indicate that APT imaging has the potential to serve as a reliable biomarker for response assessment in NPC.

A Preoperative Predictive Model of Lower Lumbar Spine Instability Based on Three-Dimensional Computed Tomography: A Retrospective Case-Control Pilot Study.

OBJECTIVE: This study aimed to build a predictive model of lower lumbar instability. METHODS: This retrospective study included 199 patients. Patients were divided into the lower lumbar instability group (LLIG) (n = 98) and lower lumbar stability group (LLSG) (n = 101). All participants of LLIG were recruited over a 2-year period (2015-2017) from the patients who accept lumbar surgery at the First Hospital of Jilin University. The LLSG was selected from outpatients who had underwent lumbar spine computed tomography (CT) and Flexion and extension radiographs (FER) at the First Hospital of Jilin University from 2015 to 2017. Several lower lumbar parameters were measured, including Lordosis angle (LA), intervertebral height (IH), ratio of anterior height to posterior height (APR), angle between endplate and anterior edge of vertebral body (AEPVa), sagittal slip ratio (SSR), and angle between the upper endplate and z-axis on sagittal plane (AUEZS). These parameters were keyed into the SPSS software to create a predictive model for classification. Sensitivity, specificity, predictive accuracy, and Kappa value were used to evaluate the predictive model. RESULTS: Compared with LLSG, the LA of LLIG decreased by 3.49° (126.54° vs 130.3°). Similarly, the IH of LLIG decreased by 1.23°mm, 1.66°mm, and 0.71°mm at L3-4, L4-5, and L5-S1. Compared with LLSG, the SSR of LLIG is higher at L3-4, L4-5, and L5-S1 (0.54 vs 0.51, 0.57 vs 0.46, and 0.59 vs 0. 47). Moreover, the APR of LLIG is higher than those of LLSG at L3-4, L4-5, and L5-S1 (1.97 vs 1.81, 2.40 vs 1.97, and 2.69 vs 2.26). The LLIG has bigger AEPVa than LLIG at L3-4, L4-5, and L5-S1. Compared with LLSG, the AUEZS of LLIG is bigger at L3-4 (91.75° vs 90.81°) and smaller at L4-5 and L5-S1(84.63° vs 85.85° and 73.27° vs 75.01°). The SSR (L4) show highest predictive accuracy (83%) when every parameter was fed to LDA classifier to generate a univariate model. All parameters represent a statistically significant difference (P < 0.05) between LLSG and LLIG. The model including LA, APR (L5-S1), IH (L4-5), SSR (L5), AUEZS (L5) has highest predictive accuracy of 88.2%. The sensitivity, specificity, and Kappa value are 88.7%, 93.1%, and 0.77. CONCLUSION: The predictive model has good classification performance and can be an auxiliary tool for clinicians to evaluate lumbar instability in preoperative patients with severe pain aggravated by lumbar movement.

Early detection treatment response for head and neck carcinomas using intravoxel incoherent motion-magnetic resonance imaging: a meta-analysis.

OBJECTIVES: To evaluate the diagnostic accuracy of intravoxel incoherent motion-MRI (IVIM-MRI) for predicting the treatment response in head and neck squamous cell carcinomas (HNSCC) patients. METHODS: A comprehensive literature search was performed to identify original articles on diagnostic performance of IVIM in predicting treatment response in HNSCC patients receiving chemoradiotherapy. The IVIM parameters studied were diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient. Summary estimates of diagnostic accuracy were obtained by using a random-effects model. Of 65 studies screened, 8 studies with 347 patients were finally included. RESULTS: The pooled sensitivities and specificities were 76% [95% confidence interval (CI) 69-82%] and 81% (95% CI 70-89%) for pre-treatment D, and 70% (95% CI 58-80%) and 82% (95% CI 66-92%) for △D, respectively. In addition, the sensitivities and specificities ranged from 41.7 to 94% and 67 to 100% for pre-treatment f, and from 55.7 to 76.5% and 72.2 to 93.3% for pre-treatment apparent diffusion coefficient, respectively. CONCLUSIONS: The diffusion-related coefficients pre-treatment D and △D demonstrated good accuracy in predicting early treatment response in HNSCC patients. However, because of the variability in reference test and other limitations of included literature, further investigation is needed before implementing any IVIM strategy into clinical practice.

Prognostic value of immune-related genes in the tumor microenvironment of lung adenocarcinoma and lung squamous cell carcinoma.

Non-small cell lung cancer (NSCLC), which consists mainly of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), are the leading cause of cancer deaths worldwide. In this study, we performed a comprehensive analysis of the tumor microenvironmental and genetic factors to identify prognostic biomarkers for NSCLC. We evaluated the immune and stromal scores of patients with LUAD and LUSC using data from The Cancer Genome Atlas database with the ESTIMATE algorithm. Based on these scores, the differentially expressed genes were obtained and immune-related prognostic genes were identified. Functional analysis and protein-protein interaction network further revealed the immune-related biological processes in which these genes participated. Additionally, 22 subsets of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment were analyzed with the CIBERSORT algorithm. Finally, we validated these valuable genes using an independent cohort from the Gene Expression Omnibus database. The associations of the immune and stromal scores with patients' clinical characteristics and prognosis were positive in LUAD but negative in LUSC and the correlations of TIICs with clinical characteristics were clarified. Several differentially expressed genes were identified to be potential immune-related prognostic genes. This study comprehensively analyzed the tumor microenvironment and presented immune-related prognostic biomarkers for NSCLC.

Thoracic gout tophus with abdominal wall protrusion: A case report.

RATIONALE: A patient presented the abdominal wall protrusion due to tophaceous gout of the spine. Similar cases were not reported in the literature. This study aimed to report a case of tophaceous gout of the spine with abdominal wall protrusion. PATIENT CONCERNS: A 38-year-old male patient had a 10-year history of gout and hyperuricemia. He complained of back pain and abdominal wall protrusion. DIAGNOSES: The patient was diagnosed with tophaceous gout of the spine with abdominal wall weakness caused by T11 nerve root compression. INTERVENTIONS: A semi-lamina decompression was performed at T11-T12. The pathological examination of the specimen demonstrated tophaceous gout of the spine. OUTCOMES: After the surgery, the patient's back pain was completely relieved and the abdominal wall weakness significant improved. LESSONS: This case highlighted that axial gout could mimic thoracic disk herniation clinically. The abdominal wall weakness might also be due to single T11 nerve compression by the tophaceous gout of the spine. In patients with a history of gout, axial gout should be considered as one of the differential diagnoses.

Placenta percreta evaluated by MRI: correlation with maternal morbidity.

PURPOSE: The purpose of this study was to evaluate the capability of MRI in depicting the topography of placenta percreta (PP) and to further explore the correlation between invasion topography and maternal outcomes. METHODS: 55 patients with histologically or surgically confirmed PP were included in this retrospective study. Two senior radiologists evaluated the topography of PP based on MR images: the invasion topography was depicted as S1, S2, parametrial, bladder, and cervical invasion. The correlation between invasion topography and maternal outcomes was analyzed using Chi-square statistic. RESULTS: MRI showed high sensitivity and specificity in delineating the invasion topography of PP (ranging from 87.5 to 100%). MRI had 100% specificity for predicting the parametrial, bladder, and cervical invasion. The rate of cesarean hysterectomy, ureteral injuries and ICU administration, and the amount of blood transfusions in PP with S2 invasion were higher than S1 invasion (P < 0.05). In addition, all patients with bladder invasion (8/8) received partial bladder resection by urologists. All the patients with S2 parametrial invasion (12/12) or cervical invasion (9/9) underwent cesarean hysterectomy. CONCLUSION: MRI was capable in predicting the invasion topography of PP patients. Moreover, PP patients with S2, parametrial, bladder or cervical invasion had more severe maternal morbidity.

Yes-associated protein (YAP) predicts poor prognosis and regulates progression of esophageal squamous cell cancer through epithelial-mesenchymal transition.

The impact of yes-associated protein (YAP) on the prognosis of patients with esophageal squamous cell cancer (ESCC) and its mechanism of action has seldom been reported. In the present study, the role of YAP on the prognosis of patients with ESCC and the mechanism of action of YAP in promoting the progression of ESCC was investigated. Tumor tissue samples from patients with ESCC were collected and the level of YAP expression was detected using immunohistochemical staining. In addition, YAP was knocked-down in ESCC cell lines and the effects on cell migration and invasion were examined. The expression levels of vimentin, N-cadherin, and E-cadherin were further investigated to examine the association between YAP and epithelial-mesenchymal transition (EMT). Results showed that overexpression of YAP was associated with larger lymph node metastasis and poor disease-free survival and overall survival. Compared with patients in early stage ESCC, the association was more significant in patients with late stage ESCC. Univariate and multivariate analyses further indicated that YAP expression could be an independent prognostic factor for ESCC. Downregulation of YAP inhibited cell migration and invasion. Western blot analysis showed that when YAP was knocked down, expression levels of vimentin and N-cadherin were reduced, whereas that of E-cadherin was increased. In conclusion, the results indicates that YAP expression level could be a novel marker for predicting the prognosis of patients with ESCC, and YAP-promoted tumor migration and invasion might be through EMT in ESCC.