Anatomical study of the relationship between the lumbar intervertebral disc, nerves, and psoas major.

Cadaveric study; To describe the characteristics of the nerve and its relationship with the lumbar intervertebral disc and psoas major muscle. Nerve injury is an understudied complication of extreme lateral interbody fusion. A detailed description of the nerve anatomy would be helpful for surgeons to minimize the risk of this complication. The lumbar plexus and lumbar sympathetic nerve of 10 embalmed male cadavers were dissected, and the distribution, number, and spatial orientation of the nerves on the L1/2 to L4/5 intervertebral discs were examined. Metal wires were applied along nerve paths through the psoas major muscle. The position of the nerves was examined on CT. In zone III at L1/2 and L4/5, no nerves were found. In zone II and zone III at L2/3, no lumbar plexus was found, and only the ramus communicans passed through. At the L1-L5 level, the density of nerves in the posterior half of the psoas major muscle was greater than that in the anterior half. The lumbar plexus was found in all of zone IV. The genitofemoral nerve emerges superficially and anteriorly from the medial border of the psoas major at the L3-4 level, but at the L1/2 level, the sympathetic trunk is located in zone II. The remaining disc-level sympathetic trunks appear in zone I. No nerves were found in zone III of the L1/2 or L4/5 disc. In zones II and III of L2/3, the lumbar plexus appears safe. The genitofemoral nerve travels through zones II and III of L3/4. The distribution density of nerves in the posterior half of the psoas major muscle was greater than that in the anterior half of that muscle at the L1-L5 level.

Position of lumbar plexus nerves in the psoas major: Application to transpsoas approaches to the lumbar spine.

Far lateral interbody fusion is a minimally invasive operating technique. However, the incidence of postoperative neurological complications is high, and some scholars question its safety. This study describes the neuroanatomical features and spatial orientation within the psoas major. Ten embalmed male cadavers were selected and the left psoas major was dissected. Subsequently, the area between the anterior and the posterior edges of the vertebral body was divided into three equal zones. The nerves' distribution, number, and spatial orientation of the L1/2 to L4/5 intervertebral discs were examined. A caliper was used to measure the diameter of the nerve. The safety zone of the L1/2 intervertebral disc level is located in zone I and II, the relative safe zones of the L2/3 and L4/5 intervertebral discs are located in zone II, and the safety zone of the L3/4 intervertebral disc level is located in the caudal side of zone II. The genitofemoral nerve exits the psoas major in a co-trunk or two-branch pattern, and its exit point was distributed between the L3 and L4 vertebral bodies, mainly at the L3/4 intervertebral disc level. The sympathetic ganglia in the psoas major appeared only in zone I at the L2/3 intervertebral disc level. This is a systematic anatomical study that describes the nerves of the psoas major. Spine surgeons can use this study-which consists of important clinical implications-for preoperative planning, and thus, reduce the risk of nerve injury during surgery.

Automated Rib Fracture Detection on Chest X-Ray Using Contrastive Learning.

To develop a deep learning-based model for detecting rib fractures on chest X-Ray and to evaluate its performance based on a multicenter study. Chest digital radiography (DR) images from 18,631 subjects were used for the training, testing, and validation of the deep learning fracture detection model. We first built a pretrained model, a simple framework for contrastive learning of visual representations (simCLR), using contrastive learning with the training set. Then, simCLR was used as the backbone for a fully convolutional one-stage (FCOS) objective detection network to identify rib fractures from chest X-ray images. The detection performance of the network for four different types of rib fractures was evaluated using the testing set. A total of 127 images from Data-CZ and 109 images from Data-CH with the annotations for four types of rib fractures were used for evaluation. The results showed that for Data-CZ, the sensitivities of the detection model with no pretraining, pretrained ImageNet, and pretrained DR were 0.465, 0.735, and 0.822, respectively, and the average number of false positives per scan was five in all cases. For the Data-CH test set, the sensitivities of three different pretraining methods were 0.403, 0.655, and 0.748. In the identification of four fracture types, the detection model achieved the highest performance for displaced fractures, with sensitivities of 0.873 and 0.774 for the Data-CZ and Data-CH test sets, respectively, with 5 false positives per scan, followed by nondisplaced fractures, buckle fractures, and old fractures. A pretrained model can significantly improve the performance of the deep learning-based rib fracture detection based on X-ray images, which can reduce missed diagnoses and improve the diagnostic efficacy.

An AI-Based Image Quality Control Framework for Knee Radiographs.

Image quality control (QC) is crucial for the accurate diagnosis of knee diseases using radiographs. However, the manual QC process is subjective, labor intensive, and time-consuming. In this study, we aimed to develop an artificial intelligence (AI) model to automate the QC procedure typically performed by clinicians. We proposed an AI-based fully automatic QC model for knee radiographs using high-resolution net (HR-Net) to identify predefined key points in images. We then performed geometric calculations to transform the identified key points into three QC criteria, namely, anteroposterior (AP)/lateral (LAT) overlap ratios and LAT flexion angle. The proposed model was trained and validated using 2212 knee plain radiographs from 1208 patients and an additional 1572 knee radiographs from 753 patients collected from six external centers for further external validation. For the internal validation cohort, the proposed AI model and clinicians showed high intraclass consistency coefficients (ICCs) for AP/LAT fibular head overlap and LAT knee flexion angle of 0.952, 0.895, and 0.993, respectively. For the external validation cohort, the ICCs were also high, with values of 0.934, 0.856, and 0.991, respectively. There were no significant differences between the AI model and clinicians in any of the three QC criteria, and the AI model required significantly less measurement time than clinicians. The experimental results demonstrated that the AI model performed comparably to clinicians and required less time. Therefore, the proposed AI-based model has great potential as a convenient tool for clinical practice by automating the QC procedure for knee radiographs.

A comparative study of the anatomy and MRI images of the lumbar foraminal ligaments at the L1-L5 levels.

PURPOSE: The purpose of this study was to evaluate the ability of MRI images to reveal foraminal ligaments at levels L1-L5 by comparing the results with those of anatomical studies. METHODS: Eighty lumbar foramina were studied. First, the best MRI scanning parameters were selected, and the transverse and sagittal axes of each lumbar foramina were scanned to identify and record the ligament-like structures in each lumbar foramen. Then, the cadaveric specimens were anatomically studied, and all ligament structures in the lumbar foramina were retained. The number, morphology and distribution of ligaments under anatomical and MRI scanning were observed. Histological staining of the dissected ligament structures was performed to confirm that they were ligamentous tissues. Finally, the accuracy of ligament recognition in MRI images was statistically analyzed. RESULTS: A total of 233 foraminal ligaments were identified in 80 lumbar intervertebral foramina through cadaveric anatomy. The radiating ligaments (176, 75.5%) were found to be attached from the nerve root to the surrounding osseous structures, while the transforaminal ligaments (57, 24.5%) traversed the intervertebral foramina without any connection to the nerve roots. A total of 42 transforaminal ligament signals and 100 radiating ligament signals were detected in the MRI images of the 80 intervertebral foramina. CONCLUSION: The MRI can identify the lumbar foraminal ligament, and the recognition rate of the transforaminal ligament is higher than that of the radiating ligament. This study provides a new method for the clinical diagnosis of the relationship between the lumbar foraminal ligament and radicular pain.

An anatomical study of the origins courses and distributions of the transverse branches of lumbar arteries at the L1-L4 levels.

Pseudoaneurysms of the lumbar arteries following transforaminal lumbar interbody fusion (TLIF) are rare postoperative complications that usually occur around the transverse process. However, there are few detailed descriptions of the transverse branch and other branches of the dorsal branches at the L1-L4 disks. STUDY DESIGN: Ten adult embalmed cadavers were anatomically studied. OBJECTIVES: The purposes of the study were to describe the vascular distribution of the dorsal branches, especially the transverse branches, at the L1-L4 levels and provide information useful for TLIF. METHODS: Ten embalmed cadavers studied after their arterial systems were injected with red latex. The quantity, origin, pathway, distribution range and diameter of the branches were recorded and photographed. RESULTS: The transverse branch appeared in all 80 intervertebral foramina. The transverse branch was divided into 2 types: In type 1, the arteries divided into superior branches and inferior branches; the arteries in type 2 divided into 3 branches (superior, intermedius and inferior branches). CONCLUSIONS: The transverse branches of the dorsal arteries are common structures from L1 to L4, and 2 types of transverse branches were found. A thorough understanding of the dorsal branches, especially the transverse branches of the lumbar artery, may be very important for reducing both intraoperative bleeding during the surgery and the occurrence of pseudoaneurysms after transforaminal lumbar interbody fusion.

Long non-coding RNA MEG3 silencing and microRNA-214 restoration elevate osteoprotegerin expression to ameliorate osteoporosis by limiting TXNIP.

Studies have shown that long non-coding RNA (lncRNA) MEG3 plays a key role in osteoporosis (OP), but its regulatory mechanism is somewhat incompletely clear. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP). Rat models of OP were established. MEG3, miR-214 and TXNIP mRNA expression in rat femoral tissues were detected, along with TXNIP, OPG and RANKL protein expression. BMD, BV/TV, Tb.N and Tb.Th in tissue samples were measured. Ca, P and ALP contents in rat serum were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ mRNA expression, PCNA, cyclin D1, OCN, RUNX2 and osteolix protein expresion, ALP content and activity, and mineralized nodule area of rat osteoblasts were further detected. Dual-luciferase reporter gene and RNA-pull down assays verified the targeting relationship between MEG3, miR-214 and TXNIP. MEG3 and TXNIP were up-regulated while miR-214 was down-regulated in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, trabecular bone area, collagen area and OPG expression, and down-regulated RANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P and reduced ALP in OP rat serum, elevated osteoblast viability, differentiation ability, COL-I and COL-Χ expression and ALP activity, and reduced COL-II expression of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP. MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by down-regulating TXNIP, which further improves OP.

CXCL2 attenuates osteoblast differentiation by inhibiting the ERK1/2 signaling pathway.

The C-X-C motif chemokine ligand 2 (CXCL2), a member of the CXC receptor ligand family, is involved in various immune and inflammatory processes, but its effect(s) on bone formation have not yet been reported. We report here that CXCL2 is enriched in bone marrow and show abundant expression of CXCL2 in osteoblasts of osteoporotic mice. CXCL2 neutralization within the bone marrow by using antibody alleviated bone loss in mice, indicating a negative role of CXCL2 in bone formation. In line with this, CXCL2 overexpression attenuated proliferation, as well as differentiation, of osteoblasts in vitro By contrast, CXCL2 downregulation promoted osteoblast expansion and differentiation. Mechanistically, CXCL2 inhibits the ERK1/2 (MAPK3/1) signaling pathway in osteoblasts. Activation of ERK1/2 abolishes the inhibitory effect of CXCL2 in osteoblasts, whereas inactivation of ERK1/2 reverses the osteogenic role of CXCL2 inhibition. These results show that CXCL2 attenuates osteoblast differentiation through inhibition of the ERK1/2 signaling pathway. We demonstrate here that CXCL2 is a negative regulator of bone formation and clarify the responsible mechanisms. Therefore, pharmaceutical coordination of CXCL2 and of the pathways through which it is regulated in osteoblasts might be beneficial regarding bone formation.

Variation in spatial distance between the lumbar interlaminar window and intervertebral disc space during flexion-extension.

PURPOSE: Knowledge of interlaminar space is important for undertaking percutaneous endoscopic discectomy via an interlaminar approach (PED-IL). However, dynamic changes in the lumbar interlaminar space and the spatial relationship between the interlaminar space and intervertebral disc space (IDS) are not clear. The aim of this study was to anatomically clarify the changes in interlaminar space height (ILH) and variation in distance between the two spaces during flexion-extension of the lumbar spine in vitro. METHODS: First, we used a validated custom-made loading equipment to obtain neutral, flexion, and extension 3D models of eight lumbar specimens through 3D reconstruction software. Changes in ILH (ILH, IL-yH, IL-zH) and distances between the horizontal plane passing through the lowest edge of the lamina of the superior lumbar vertebrae and the horizontal plane passing through the lowest position of the trailing edge of the same-level IDS (DpLID) at L3/4, L4/5 and L5/S1 were examined on 3D lumbar models. RESULTS: We found that ILH was greater at L4/5 than at L3/4 and L5/S1 in the neutral position, but the difference was not significant. In the flexion position, ILH was significantly more than that in neutral and extension positions at L3/4, L4/5, and L5/S1. There were significantly more DpLID changes from neutral to flexion than that from neutral to extension at all levels (L3/4, L4/5, L5/S1). CONCLUSION: These findings demonstrated level-specific changes in ILH and DpLID during flexion-extension. The data may provide a better understanding of the spatial relationship between lumbar interlaminar space and IDS, and aid the development of segment-specific treatment for PED-IL.

Characteristics of disease distribution for the 1 370 renal biopsy cases in two hospitals from Guilin and Jining. / 桂林和济宁两所医院1 370ä¾‹è‚¾æ´»æ£€ç–¾ç— åˆ†å¸ƒç‰¹å¾.

OBJECTIVES: To analyze the constitution and distribution characteristics of renal pathological disease spectrum in the 2 hospitals from Guilin city and Jining city in recent 5 years. METHODS: The pathological results of inpatients with renal biopsy in the 2 hospitals from Guilin city and Jining city from April 1, 2014 to August 15, 2018 were retrospectively analyzed. A total of 1 370 renal biopsy cases were collected, including 706 cases in Affiliated Hospital of Jining Medical College (Jiyi) and 664 cases in Affiliated Hospital of Guilin Medical College (Guiyi). RESULTS: There was no significant difference in gender, age, seasonal distribution and the total proportion of primary and secondary glomerular diseases between the 2 hospitals (all P>0.05). The ratio of male to female in the 2 hospitals was 1.18 (Jiyi) and 0.98 (Guiyi). IgA nephropathy (IgAN) was the major disease in 14-30 years old patients, and membranous nephropathy (MN) was the most common in 40-50 years old patients. There are 15 kinds of same diseases and 10 kinds of different diseases in the 2 hospitals. Among them, three pathological diseases (3 cases) including obesity-related nephropathy, primary Sjogren's syndrome renal damage, and pregnancy-induced hypertensive renal damage only appeared in Jiyi, while 7 diseases (55 cases) including focal segmental glomerulosclerosis (FSGS), focal proliferative glomerulonephritis (FGN), proliferative sclerosing glomerulonephritis (PSGN), endocapillary proliferative glomerulonephritis (EPGN), multiple myeloma renal damage, eosinophilic tumor renal damage and angiomyolipoma renal damage only appeared in Guiyi. Primary glomerular diseases (82% in Jiyi/79% in Guiyi) were higher than secondary nephropathy. The top two diseases in biopsy rate were MN and IgAN. The incidence rate of some diseases in Jiyi was higher than that in Guiyi, and these diseases included MN (48.87%, 31.78%), minimal change disease (MCD) (11.47%, 2.71%), allergic purpura nephritis (Henoch-Schlein purpura nephritis, HSPN) (3.97%, 1.51%), hypertensive renal damage (3.12%, 0.15%), diabetic nephropathy (DN) (2.97%, 1.36%). The incidence rate of other diseases in Guiyi were higher than that in Jiyi, and these diseases included IgAN (22.59%, 19.14%), mesangial proliferative glomerulonephritis (MsPGN) (11.45%, 0.99%), lupus nephritis (LN) (8.58%, 4.67%), hepatitis B virus associated nephritis (HBVGN) (7.53%, 1.84%), there were significant difference between the 2 hospitals in the above diseases (all P<0.05). CONCLUSIONS: The disease distribution of renal biopsy cases in the 2 hospitals displays both similarities and characteristics. Primary glomerular disease is still the main disease. MN has surpassed IgAN and jumped to the first place. The high incidence age of MN is 40-50 years old, and IgAN is 14-30 years old. The incidence rates of MN, MCD, HSPN, hypertensive renal damage, DN and other related diseases of air quality and lifestyle in Jiyi are higher than those in Guiyi. IgAN, MsPGN, LN, HBVGN and other diseases related to infection and tumor factors were higher in Guiyi than those in Jiyi. The prevention and control strategies in the 2 regions need to be adapted to local conditions. More attention should be paid to the impact of environment and lifestyle on kidney health in East China. We should pay attention to the damage to kidney caused by infectious diseases in Southern China, especially in female patients.

MicroRNA-497 elevation or LRG1 knockdown promotes osteoblast proliferation and collagen synthesis in osteoporosis via TGF-ß1/Smads signalling pathway.

MicroRNAs (miRNAs) have been corroborated to engage in the process of cellular activities in osteoporosis. However, few researches have been conducted to expose the integrated role of miR-497, leucine-rich alpha-2-glycoprotein-1 (LRG1) and transforming growth factor beta 1 (TGF-ß1)/Smads signalling pathway in osteoporosis. Thereafter, the study is set out to delve into miR-497/LRG1/TGF-ß1/Smads signalling pathway axis in osteoporosis. Osteoporosis bone tissues and normal bone tissues were collected. Rat osteoporosis models were constructed via ovariectomy. Model rats were injected with restored miR-497 or depleted LRG1 to explore their roles in osteoporosis. Rat osteoblasts were extracted from osteoporosis rats and transfected with restored miR-497 or depleted LRG1 for further verification. MiR-497 and LRG1 expression in femoral head tissues and osteoblasts of osteoporosis rats were detected. TGF-ß1/Smads signalling pathway-related factors were detected. MiR-497 was poorly expressed while LRG1 was highly expressed and TGF-ß1/Smads signalling pathway activation was inhibited in osteoporosis. MiR-497 up-regulation or LRG1 down-regulation activated TGF-ß1/Smads signalling pathway, promoted collagen type 1 synthesis and suppressed oxidative stress in femoral head tissues in osteoporosis. MiR-497 restoration or LRG1 knockdown activated TGF-ß1/Smads signalling pathway, promoted viability and suppressed apoptosis of osteoblasts in osteoporosis. Our study suggests that miR-497 up-regulation or LRG1 down-regulation promotes osteoblast viability and collagen synthesis via activating TGF-ß1/Smads signalling pathway, which may provide a novel reference for osteoporosis treatment.

Urinary Matrix Metalloproteinase 7 and Prediction of IgA Nephropathy Progression.

RATIONALE & OBJECTIVE: A major challenge in the management of immunoglobulin A nephropathy (IgAN) is the inability to identify patients at high risk for disease progression at an early stage. Our objective was to determine whether urinary matrix metalloproteinase 7 (MMP-7) is a promising predictor for IgAN progression and whether its addition to clinical data at the time of biopsy improves risk prediction. STUDY DESIGN: Prospective observational cohort study in China. SETTING & PARTICIPANTS: 946 Chinese patients with IgAN followed up for a median of 40 months in 1 clinical center serving as the training set (n=554) and for 28 months in a second clinical center serving as the validation set (n = 392). PREDICTORS: Urinary MMP-7 and 7 previously reported biomarkers measured at the time of kidney biopsy and a score of histologically defined disease severity (MEST-C). OUTCOMES: IgAN progression was defined as a composite of >40% loss of estimated glomerular filtration rate, kidney failure, or death. ANALYTICAL APPROACH: Cox proportional hazard models adjusted for clinical characteristics, kidney function, relevant medications, and MEST-C score. Risk classification statistics were calculated for IgAN progression at 3 years, including C statistic, net reclassification index, and integrated discrimination index. RESULTS: High levels (>3.9µg/g of creatinine) of urinary MMP-7 were associated with a 2.7-fold higher risk for IgAN progression in adjusted analyses. Urinary MMP-7 level outperformed (C statistic, 0.78) levels of urinary angiotensinogen (C statistic, 0.75), epidermal growth factor (C statistic, 0.75), kidney injury molecule 1 (C statistic, 0.68), and serum galactose-deficient IgA1 (C statistic, 0.59) for predicting IgAN progression. The addition of urinary MMP-7 level to a model with clinical data from the time of biopsy (estimated glomerular filtration rate, mean arterial blood pressure, and proteinuria) and MEST-C score significantly improved the C statistic from 0.79 to 0.85, improved the 3-year risk prediction of IgAN progression (from 0.84 to C statistic of 0.90), and improved risk reclassification (category-free net reclassification improvement, 0.60). The predictive performance of urinary MMP-7 level, alone or combined with clinical data, was consistent in the external validation set. LIMITATIONS: Lack of validation in other ethnic populations. CONCLUSIONS: In this study cohort, urinary MMP-7 level is an independent predictor of IgAN progression. The addition of urinary MMP-7 level to MEST-C score and clinical data at the time of biopsy significantly improved risk prediction of IgAN progression.

Dysregulated circRNA_100876 suppresses proliferation of osteosarcoma cancer cells by targeting microRNA-136.

The aim of this study was to explore the regulatory mechanism of circRNA_100876/ microRNA-136 (miR-136) axis in the development and progression of osteosarcoma cancer. Quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate the expression levels of circRNA_100876 and miR-136 in osteosarcoma cancer samples and the adjacent nontumor tissues. Then, cell proliferation, cell cycle, apoptosis, and migration of circRNA_100876-knocked down cells were analyzed by in vitro and in vivo experiments, using cell counting kit-8 (CCK-8), flow cytometry, and transwell and tumorigenesis assays. The expression of circRNA_100876 was found to be significantly upregulated in osteosarcoma, and was closely correlated with the tumor size and tumor differentiation degree. In addition, the knockdown of circRNA_100876 could significantly inhibit the tumor growth, both in vitro and in vivo. Flow cytometry and Western blot analysis results showed that the downregulation of circRNA_100876 inhibited osteosarcoma cells proliferation via promoting apoptosis and arresting more cells in the G2/M stage, as suggested by the expression of apoptosis and cell cycle pathway-related proteins, which changed consistently. Furthermore, the level of miR-136 was negatively correlated with the expression of circRNA_100876, and miR-136 inhibitors were able to reverse the suppression of cell proliferation induced by silencing circRNA_100876. Our study demonstrates that the dysregulation of circRNA_100876 could induce apoptosis and arrest the cell cycle at G2/M stage, followed by suppression of cell proliferation in osteosarcoma, while silencing miR-136 could restore the cell growth. Therefore, circRNA_100876 might serve as a promising biomarker and treatment target for osteosarcoma.

Changes in quantitative parameters of pulmonary nonsolid nodule induced by lung inflation according to paired inspiratory and expiratory computed tomography imaging.

OBJECTIVE: To evaluate quantitative parameters of nonsolid nodules on paired inspiratory and expiratory computed tomography (CT) and to examine whether these parameters are sensitive to lung inflation reflected by lung volume. METHODS: Thirty-three patients with 41 nonsolid nodules were included in this prospective study. Paired inspiratory and low-dose respiratory plain chest CT were performed. The volume and density of nonsolid nodule(s), both lungs, the right and left lung, and five lobes, were analyzed in inspiratory and expiratory CT scans. The ratio of expiratory to inspiratory parameters was calculated and labeled as parameter(E-I)/I. To standardize the changes in nonsolid nodule quantitative parameters, the ratio of nonsolid nodule parameter to lung parameter was also calculated. Quantitative parameters were compared between inspiratory and expiratory CT. RESULTS: Nonsolid nodule volumes on expiratory CT were reduced by 19.8% ± 12.9%, while the density was increased by 11.4% ± 8.8%. The volume of nonsolid nodules was significantly greater on inspiratory compared with expiratory CT (p < 0.001). The density of nonsolid nodules was significantly greater on expiratory than inspiratory CT (p < 0.001). The volume(E-I)/I was significantly greater than density(E-I)/I both in nonsolid nodules and lung. The volume(E-I)/I and density(E-I)/I of nonsolid nodules were independent of size. The density(E-I)/I of nonsolid nodule was greater in the lower lobe than that in the upper lobe (p = 0.002). CONCLUSION: Volume changes in nonsolid nodules were more sensitive than density changes in expiratory phase. The density of lower lobe nodules was more susceptible to respiration. Expiratory scanning is not recommended for quantification of nonsolid nodules and/or follow-up. KEY POINTS: • The nonsolid nodule volume on expiratory CT was reduced by 19.8% ± 12.9%. • The nonsolid nodule density on expiratory CT was increased by 11.4% ± 8.8%. • The volume (E-I)/I and density (E-I)/I of nonsolid nodules were independent of size.

Can peritumoral radiomics increase the efficiency of the prediction for lymph node metastasis in clinical stage T1 lung adenocarcinoma on CT?

OBJECTIVES: To evaluate the efficiency of radiomics model on CT images of intratumoral and peritumoral lung parenchyma for preoperative prediction of lymph node (LN) metastasis in clinical stage T1 peripheral lung adenocarcinoma patients. METHODS: Three hundred sixty-six peripheral lung adenocarcinoma patients with clinical stage T1 were evaluated using five CT scanners. For each patient, two volumes of interest (VOIs) on CT were defined as the gross tumor volume (GTV) and the peritumoral volume (PTV, 1.5 cm around the tumor). One thousand nine hundred forty-six radiomic features were obtained from each VOI, and then refined for reproducibility and redundancy. The refined features were investigated for usefulness in building radiomic signatures by mRMR feature ranking method and LASSO classifier. Multivariable logistic regression analysis was used to develop a radiomic nomogram incorporating the radiomic signature and clinical parameters. The prediction performance was evaluated on the validation cohort. RESULTS: The radiomic signatures using the features of GTV and PTV showed a good ability in predicting LN metastasis with an AUC of 0.829 (95% CI, 0.745-0.913) and 0.825 (95% CI, 0.733-0.918), respectively. By incorporating the features of GTV and PTV, the AUC of radiomic signature increased to 0.843 (95% CI, 0.770-0.916). The AUC of radiomic nomogram was 0.869 (95% CI, 0.800-0.938). CONCLUSIONS: Radiomic signatures of GTV and PTV both had a good prediction ability in the prediction of LN metastasis, and there is no significant difference of AUC between the two groups. The proposed nomogram can be conveniently used to facilitate the preoperative prediction of LN metastasis in T1 peripheral lung adenocarcinomas. KEY POINTS: • Radiomics from peritumoral lung parenchyma increase the efficiency of the prediction for lymph node metastasis in clinical stage T1 lung adenocarcinoma on CT. • A radiomic nomogram was developed and validated to predict LN metastasis. • Different scan parameters on CT showed that radiomics signature had good predictive performance.

Blocking C/EBP ß protects vascular endothelial cells from injury induced by intermittent hypoxia.

BACKGROUND: Intermittent hypoxia (IH) can damage endothelial cells and lead to apoptosis in obstructive sleep apnea-hypopnea syndrome (OSAHS). Hypoxia induces apoptosis in endothelial cells via upregulation of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1α) plays a key role in the hypoxic stress response. PURPOSE: We investigated an approach to diminish the negative effect of HIF-1α while maintaining its protective effect. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to sustained hypoxia (SH) or IH for 24 h, and the responses of HIF-1α, CCAAT/enhancer binding protein beta (C/EBP ß), and endothelin-1 (ET-1) were assessed by western blotting. A luciferase reporter system was employed to verify the potential binding site (transcription factor binding site, TFBS) for C/EBP ß in the ET-1 promoter. The specificity of regulation of ET-1 by HIF-1α via C/EBP ß was evaluated by a lentiviral system. The effects of silencing of C/EBP ß on IH-induced apoptosis, vascular endothelial growth factor (VEGF) protein levels, proliferation, and in vitro tube formation were studied. RESULTS: We found that IH significantly increased HIF-1α, C/EBP ß, and ET-1 in HUVECs. Knockdown of HIF-1α or C/EBP ß inhibited the upregulation of ET-1 induced by IH. Blocking C/EBP ß impaired IH-induced apoptosis but did not affect VEGF expression, proliferation, or in vitro tube formation. C/EBP ß was shown to mediate increased ET-1 transcription by HIF-1α through the TFBS, 5'-GTTGCCTGTTG-3', in ET-1 promoter. CONCLUSION: Silencing of C/EBP ß can suppress apoptosis but does not affect the protective role of HIF-1α in the hypoxic stress response.

A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum Creatinine.

BACKGROUND: Current definitions of AKI do not take into account serum creatinine's high variability in children. METHODS: We analyzed data from 156,075 hospitalized children with at least two creatinine tests within 30 days. We estimated reference change value (RCV) of creatinine on the basis of age and initial creatinine level in children without kidney disease or known AKI risk, and we used these data to develop a model for detecting pediatric AKI on the basis of RCV of creatinine. We defined pediatric AKI according to pediatric reference change value optimized for AKI in children (pROCK) as creatinine increase beyond RCV of creatinine, which was estimated as the greater of 20 µmol/L or 30% of the initial creatinine level. RESULTS: Of 102,817 children with at least two serum creatinine tests within 7 days, 5432 (5.3%) had AKI as defined by pROCK compared with 15,647 (15.2%) and 10,446 (10.2%) as defined by pediatric RIFLE (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO), respectively. Children with pROCK-defined AKI had significantly increased risk of death (hazard ratio, 3.56; 95% confidence interval, 3.15 to 4.04) compared with those without AKI. About 66% of patients with pRIFLE-defined AKI and 51% of patients with KDIGO-defined AKI, mostly children with initial creatinine level of <30 µmol/L, were reclassified as non-AKI by pROCK, and mortality risk in these children was comparable with risk in those without AKI by all definitions. CONCLUSIONS: pROCK criterion improves detection of "true" AKI in children compared with earlier definitions that may lead to pediatric AKI overdiagnosis.

A functional copy-number variation in MAPKAPK2 predicts risk and prognosis of lung cancer.

Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) may promote cancer development and progression by inducing tumorigenesis and drug resistance. To assess whether the copy-number variation g.CNV-30450 located in the MAPKAPK2 promoter has any effect on lung cancer risk or prognosis, we investigated the association between g.CNV-30450 and cancer risk in three independent case-control studies of 2,332 individuals with lung cancer and 2,457 controls and the effects of g.CNV-30450 on cancer prognosis in 1,137 individuals with lung cancer with survival data in southern and eastern Chinese populations. We found that those subjects who had four copies of g.CNV-30450 had an increased cancer risk (odds ratio = 1.94, 95% confidence interval [CI] = 1.61-2.35) and a worse prognosis for individuals with lung cancer (with a median survival time of only 9 months) (hazard ratio = 1.47, 95% CI = 1.22-1.78) compared with those with two or three copies (with a median survival time of 14 months). Meanwhile, four copies of g.CNV-30450 significantly increased MAPKAPK2 expression, both in vitro and in vivo, compared with two or three copies. Our study establishes a robust association between the functional g.CNV-30450 in MAPKAPK2 and risk as well as prognosis of lung cancer, and it presents this functional copy-number variation as a potential biomarker for susceptibility to and prognosis for lung cancer.

The value of T1- and FST2-Weighted-based radiomics nomogram in differentiating pleomorphic adenoma and Warthin tumor.

PURPOSE: To establish a radiomics nomogram based on MRI radiomics features combined with clinical characteristics for distinguishing pleomorphic adenoma (PA) from warthin tumor (WT). METHODS: 294 patients with PA (n = 159) and WT (n = 135) confirmed by histopathology were included in this study between July 2017 and June 2023. Clinical factors including clinical data and MRI features were analyzed to establish clinical model. 10 MRI radiomics features were extracted and selected from T1WI and FS-T2WI, used to establish radiomics model and calculate radiomics scores (Rad-scores). Clinical factors and Rad-scores were combined to serve as crucial parameters for combined model. Through Receiver operator characteristics (ROC) curve and decision curve analysis (DCA), the discriminative values of the three models were qualified and compared, the best-performing combined model was visualized in the form of a radiomics nomogram. RESULTS: The combined model demonstrated excellent discriminative performance for PA and WT in the training set (AUC=0.998) and testing set (AUC=0.993) and performed better compared with the clinical model and radiomics model in the training set (AUC=0.996, 0.952) and testing model (AUC=0.954, 0.849). The DCA showed that the combined model provided more overall clinical usefulness in distinguishing parotid PA from WT than another two models. CONCLUSION: An analytical radiomics nomogram based on MRI radiomics features, incorporating clinical factors, can effectively distinguish between PA and WT.