Assessing renal interstitial fibrosis using compartmental, non-compartmental, and model-free diffusion MRI approaches.

OBJECTIVE: To assess renal interstitial fibrosis (IF) using diffusion MRI approaches, and explore whether corticomedullary difference (CMD) of diffusion parameters, combination among MRI parameters, or combination with estimated glomerular filtration rate (eGFR) benefit IF evaluation. METHODS: Forty-two patients with chronic kidney disease were included, undergoing MRI examinations. MRI parameters from apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), and diffusion-relaxation correlated spectrum imaging (DR-CSI) were obtained both for renal cortex and medulla. CMD of these parameters was calculated. Pathological IF scores (1-3) were obtained by biopsy. Patients were divided into mild (IF = 1, n = 23) and moderate-severe fibrosis (IF = 2-3, n = 19) groups. Group comparisons for MRI parameters were performed. Diagnostic performances were assessed by the receiver operator's curve analysis for discriminating mild from moderate-severe IF patients. RESULTS: Significant inter-group differences existed for cortical ADC, IVIM-D, IVIM-f, DKI-MD, DR-CSI VB, and DR-CSI VC. Significant inter-group differences existed in ΔADC, ΔMD, ΔVB, ΔVC, ΔQB, and ΔQC. Among the cortical MRI parameters, VB displayed the highest AUC = 0.849, while ADC, f, and MD also showed AUC > 0.8. After combining cortical value and CMD, the diagnostic performances of the MRI parameters were slightly improved except for IVIM-D. Combining VB with f brings the best performance (AUC = 0.903) among MRI bi-variant models. A combination of cortical VB, ΔADC, and eGFR brought obvious improvement in diagnostic performance (AUC 0.963 vs 0.879, specificity 0.826 vs 0.896, and sensitivity 1.000 vs 0.842) than eGFR alone. CONCLUSION: Our study shows promising results for the assessment of renal IF using diffusion MRI approaches. CRITICAL RELEVANCE STATEMENT: Our study explores the non-invasive assessment of renal IF, an independent and effective predictor of renal outcomes, by comparing and combining diffusion MRI approaches including compartmental, non-compartmental, and model-free approaches. KEY POINTS: Significant difference exists for diffusion parameters between mild and moderate-severe IF. Generally, cortical parameters show better performance than corresponding CMD. Bi-variant model lifts the diagnostic performance for assessing IF.

Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) is one of the major causes of cancer­related death worldwide. Cisplatin is a front­line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin­mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription­quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS­mediated endoplasmic reticulum stress, and the C­Jun­amino­terminal kinase and p38 mitogen­activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS­mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.

Study on the Mechanism of Yadanzi Oil in Treating Lung Cancer Based on Network Pharmacology and Molecular Docking Technology.

Brucea javanica oil emulsion (BJOE) is a compound Chinese medicine used for treating various cancers, such as lung cancer. However, the exact mechanism of its antilung cancer active ingredient remains unclear. This study aims to explore and validate the effective active ingredients and mechanism of action of BJOE in the treatment of lung cancer through network pharmacology, molecular docking technology, and cell experiments. The results showed that there were 13 active ingredients, 136 target genes, and 42 disease target-coexpressed genes in BJOE. The molecular docking results indicated that the main active components of the oil emulsion, YD1 (ß-sitosterol), YD2 (luteolin), and YD3 (bruceitol), could stably bind to TP53 and MAPK1. Furthermore, the commercially available ß-sitosterol luteolin was used as a representative compound to conduct cell experiments to verify its anticancer activity and mechanism. It was found that luteolin can inhibit the proliferation better than ß-sitosterol and the activity of lung cancer cells by regulating the expression of related proteins through the P53/MAPK1 signaling pathway. This study combines network pharmacology prediction with experiments to demonstrate the "multicomponent, multitarget, multipathway" approach of B. javanica oil emulsion in treating lung cancer.

Dihydroartemisinin, a potential PTGS1 inhibitor, potentiated cisplatin-induced cell death in non-small cell lung cancer through activating ROS-mediated multiple signaling pathways.

Dihydroartemisinin (DHA) exerts an anti-tumor effect in multiple cancers, however, the molecular mechanism of DHA and whether DHA facilitates the anti-tumor efficacy of cisplatin in non-small cell lung cancer (NSCLC) are unclear. Here, we found that DHA potentiated the anti-tumor effects of cisplatin in NSCLC cells by stimulating reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress, C-Jun-amino-terminal kinase (JNK) and p38 MAPK signaling pathways both in vitro and in vivo. Of note, we demonstrated for the first time that DHA inhibits prostaglandin G/H synthase 1 (PTGS1) expression, resulting in enhanced ROS production. Importantly, silencing PTGS1 sensitized DHA-induced cell death by increasing ROS production and activating ER-stress, JNK and p38 MAPK signaling pathways. In summary, our findings provided new experimental basis and therapeutic prospect for the combined therapy with DHA and cisplatin in some NSCLC patients.

The association of cervical sagittal alignment with anterior bone loss following single-level anterior cervical surgery.

Background: Anterior bone loss (ABL) is a common phenomenon after cervical disc replacement (CDR), which can also be observed after anterior cervical discectomy and fusion (ACDF). This study aimed to investigate the incidence and severity of ABL in single-level CDR and ACDF and explore the association of cervical sagittal alignment with ABL. Methods: This is a single-center retrospective cohort study. A total of 113 patients treated with CDR and 99 patients treated with ACDF were retrospectively reviewed from January 2014 to December 2018 in West China Hospital. Radiological data were collected at pre-operation, 1 week, 3 months postoperatively, and the last follow-up. The incidence and severity of ABL after both CDR and ACDF were evaluated. Cervical sagittal alignment parameters, including C0-C2 angle, cervical lordosis (CL), C2-C7 sagittal vertical axis (cSVA), T1 slope, functional spinal unit angle, disc angle, and surgical level slope, were evaluated. Results: ABL was identified in 75 (66.4%) patients in the CDR group and 57 (57.6%) patients in the ACDF group. There were no significant differences in the incidence, severity, and location of ABL between the ACDF and CDR groups. For patients who underwent ACDF, the proportion of females was significantly higher in the ABL group (64.9% vs. 33.3%, P=0.002), whereas the body mass index (BMI) was significantly lower in the ABL group compared to the non-ABL group (22.72±3.09 vs. 24.60±3.04, P=0.002). No effect of ABL on the short-term clinical outcomes of ACDF and CDR was observed. In the ACDF group, patients with ABL had significantly smaller postoperative CL (11.83°±8.24° vs. 15.25°±8.32°, P=0.04) and cSVA (17.77±10.08 vs. 23.35±9.86 mm, P=0.007). In the CDR group, no significant differences were found in the cervical sagittal parameters between patients with and without ABL (CL: 12.58±8.70 vs. 15.46±8.50, P=0.10; cSVA: 20.95±8.54 vs. 19.40±9.43, P=0.38). Conclusions: ABL is common after both CDR and ACDF with comparable incidence and severity. Cervical sagittal alignment was closely related to ABL after ACDF yet had less influence on ABL after CDR.

Artificial intelligence can accurately distinguish IgA nephropathy from diabetic nephropathy under Masson staining and becomes an important assistant for renal pathologists.

Introduction: Hyperplasia of the mesangial area is common in IgA nephropathy (IgAN) and diabetic nephropathy (DN), and it is often difficult to distinguish them by light microscopy alone, especially in the absence of clinical data. At present, artificial intelligence (AI) is widely used in pathological diagnosis, but mainly in tumor pathology. The application of AI in renal pathological is still in its infancy. Methods: Patients diagnosed as IgAN or DN by renal biopsy in First Affiliated Hospital of Zhejiang Chinese Medicine University from September 1, 2020 to April 30, 2022 were selected as the training set, and patients who diagnosed from May 1, 2022 to June 30, 2022 were selected as the test set. We focused on the glomerulus and captured the field of the glomerulus in Masson staining WSI at 200x magnification, all in 1,000 × 1,000 pixels JPEG format. We augmented the data from training set through minor affine transformation, and then randomly split the training set into training and adjustment data according to 8:2. The training data and the Yolov5 6.1 algorithm were used to train the AI model with constant adjustment of parameters according to the adjusted data. Finally, we obtained the optimal model, tested this model with test set and compared it with renal pathologists. Results: AI can accurately detect the glomeruli. The overall accuracy of AI glomerulus detection was 98.67% and the omission rate was only 1.30%. No Intact glomerulus was missed. The overall accuracy of AI reached 73.24%, among which the accuracy of IgAN reached 77.27% and DN reached 69.59%. The AUC of IgAN was 0.733 and that of DN was 0.627. In addition, compared with renal pathologists, AI can distinguish IgAN from DN more quickly and accurately, and has higher consistency. Discussion: We constructed an AI model based on Masson staining images of renal tissue to distinguish IgAN from DN. This model has also been successfully deployed in the work of renal pathologists to assist them in their daily diagnosis and teaching work.

Biomechanical performance of the novel assembled uncovertebral joint fusion cage in single-level anterior cervical discectomy and fusion: A finite element analysis.

Introduction: Anterior cervical discectomy and fusion (ACDF) is widely accepted as the gold standard surgical procedure for treating cervical radiculopathy and myelopathy. However, there is concern about the low fusion rate in the early period after ACDF surgery using the Zero-P fusion cage. We creatively designed an assembled uncoupled joint fusion device to improve the fusion rate and solve the implantation difficulties. This study aimed to assess the biomechanical performance of the assembled uncovertebral joint fusion cage in single-level ACDF and compare it with the Zero-P device. Methods: A three-dimensional finite element (FE) of a healthy cervical spine (C2-C7) was constructed and validated. In the one-level surgery model, either an assembled uncovertebral joint fusion cage or a zero-profile device was implanted at the C5-C6 segment of the model. A pure moment of 1.0 Nm combined with a follower load of 75 N was imposed at C2 to determine flexion, extension, lateral bending, and axial rotation. The segmental range of motion (ROM), facet contact force (FCF), maximum intradiscal pressure (IDP), and screw-bone stress were determined and compared with those of the zero-profile device. Results: The results showed that the ROMs of the fused levels in both models were nearly zero, while the motions of the unfused segments were unevenly increased. The FCF at adjacent segments in the assembled uncovertebral joint fusion cage group was less than that that of the Zero-P group. The IDP at the adjacent segments and screw-bone stress were slightly higher in the assembled uncovertebral joint fusion cage group than in those of the Zero-P group. Stress on the cage was mainly concentrated on both sides of the wings, reaching 13.4-20.4 Mpa in the assembled uncovertebral joint fusion cage group. Conclusion: The assembled uncovertebral joint fusion cage provided strong immobilization, similar to the Zero-P device. When compared with the Zero-P group, the assembled uncovertebral joint fusion cage achieved similar resultant values regarding FCF, IDP, and screw-bone stress. Moreover, the assembled uncovertebral joint fusion cage effectively achieved early bone formation and fusion, probably due to proper stress distributions in the wings of both sides.

Exploration of Interstitial Fibrosis in Chronic Kidney Disease by Diffusion-Relaxation Correlation Spectrum MR Imaging: A Preliminary Study.

BACKGROUND: Renal interstitial fibrosis is one of the most common pathways in the progression of chronic kidney disease (CKD). Noninvasive evaluation of interstitial fibrosis would help monitoring CKD progression and prognosis prediction. PURPOSE: To evaluate the severity of renal interstitial fibrosis by diffusion-relaxation correlation spectrum imaging (DR-CSI). STUDY TYPE: Prospective. SUBJECTS: Forty patients with CKD and 10 healthy controls (average age 49.2 ± 14.8 years, 18 females). FIELD STRENGTH/SEQUENCE: 3-T, DR-CSI with 36 axial spin-echo echo-planar diffusion-weighted images (6 b-values, 6 echo times). ASSESSMENT: Interstitial fibrosis level (IFL) was assessed from biopsy results (IFL = 1, fibrosis percentage <25%, defined as mild; IFL = 2, 25%-50%, moderate; IFL = 3, >50%, severe). Estimated glomerular filtration rate (eGFR) was calculated using serum creatinine. The regions of interest included cortex for both kidneys. The diffusivity-T2 spectrum was assessed considering three compartments (threshold: T2 30-40 msec, diffusivity 5-9 µm2 /msec, according to visible peaks): A (low diffusivity, short T2), B (low diffusivity, long T2), and C (high diffusivity). Volume fractions Vi (i = A, B, C) were calculated. STATISTICAL TESTS: Intra-class coefficient (ICC, >0.6 as good) to assess inter-reader agreement of DR-CSI Vi . Spearman's correlation to assess relationship of Vi to IFL and eGFR. Receiver operating characteristic analyses with the area under the curve (AUC) to discriminate patients with moderate-severe fibrosis from mild ones. Statistical significance criteria: P-value <0.05. RESULTS: ICCs were good for all Vi . Correlations were found between IFL and VB (r = 0.424, significant) and VC (r = -0.400, significant), and between eGFR and VB (r = -0.303, P = 0.058) and VC (r = 0.487, significant). Regarding VB and VC , the AUCs were 0.903 and 0.824. DATA CONCLUSION: DR-CSI help distinguish patients with moderate or severe renal interstitial fibrosis from mild ones. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.

Accelerated Perioperative Rehabilitation for Breast Cancer Patients Undergoing Radical Mastectomy: A Systematic Review.

PURPOSE: To summarize and analyze available evidence on perioperative accelerated rehabilitation programs for patients diagnosed with breast cancer that have had a radical mastectomy. DESIGN: This article is a systematic review of literature based on evidence-based methodology. METHODS: The '6S' evidence resource pyramid model was used to systematically search a range of databases. FINDINGS: A total of 19 articles were extracted from the literature and used in this study, including 9 clinical decisions, 4 systematic evaluations, 4 expert consensuses, and 2 guidelines. We summarized a total of 47 lines of evidence with regard to various aspects, including preoperative, intraoperative, and postoperative nursing measures. CONCLUSIONS: In this systematic review, an evidence-based methodology was used to summarize and analyze the best suggestions for perioperative accelerated rehabilitation nursing programs for breast cancer inpatients undergoing radical mastectomy. We aimed to provide a good reference value and evidence-based guidelines for the continuous improvement and development of nursing practice for the breast cancer patient population.

In-Well Ionization from Monolayer Quantum Dots for Non-Carrier-Injection Electroluminescence.

Quantum dot (QD) light-emitting devices operating in non-carrier-injection (NCI) mode have attracted intense interest. Revealing the source of carriers that support the periodic electroluminescence is important because there is no injection of carriers from the external electrode. Electrons/holes generated by well-to-well multiple ionization in adjacent QDs are generally recognized as the carrier source for electroluminescence, and the stacked QD layers are necessary. In this work, NCI electroluminescence (NCI-EL) from monolayer QDs is successfully demonstrated, which cannot be properly explained by the previously proposed mechanism of multiple ionization. A working mechanism related to periodic in-well ionization is proposed, in which electrons tunnel directly from the valence band of QDs to the conduction band to form free electrons and holes. The effects of driving voltage amplitude, frequency, and QD size on the NCI-EL performance are investigated. Finite element simulation is used to clarify the ionization process. We believe this work can extend the working mechanism model of NCI-EL from QDs and provide guidance for promoting QD-based light-emitting device performance.

Effect of perioperative steroids application on dysphagia, fusion rate, and visual analogue scale (VAS) following anterior cervical spine surgery: A meta-analysis of 14 randomized controlled trials (RCTs).

Objective: To conduct a high-level meta-analysis of the RCTs to evaluate perioperative steroids use in the management of fusion rate, dysphagia, and VAS following anterior cervical spine surgery for up to 1 year. Methods: We searched the database PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, Ovid, and ClinicalTrials.gov without time restriction to identify RCTs that evaluate the effectiveness of perioperative steroids after anterior cervical spine surgery. A subgroup analysis was undertaken to investigate the effects of intravenous and local steroids. This study was registered in the PROSPERO database prior to initiation (CRD42022313444). Results: A total of 14 RCTs were eligible for final inclusion. This meta-analysis showed that steroids could achieve lower dysphagia rate (p < 0.001), severe dysphagia rate within 1 year (p < 0.001), lower VAS scores at both 1 day (p = 0.005), 2 weeks (p < 0.001) and shorter hospital stay (p = 0.014). However, there was no significant difference between the two groups regarding operation time (p = 0.670), fusion rates (p = 0.678), VAS scores at 6 months (p = 0.104) and 1 year (p = 0.062). There was no significant difference between intravenous and local steroid administration regarding dysphagia rates (p = 0.82), fusion rate (p = 1.00), and operative time (p = 0.10). Conclusion: Steroids intravenously or locally following anterior cervical spine surgery can reduce incidence and severity of dysphagia within 1 year, VAS score within 2 weeks, and shorten the length of hospital stay without affecting fusion rates, increasing the operating time, VAS score at 6 months and 1 year.

Association of Craniocervical Sagittal Alignment With the Outcomes of Cervical Disc Replacement.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To explore the association between craniocervical sagittal balance and clinical and radiological outcomes of cervical disc replacement (CDR). METHODS: Patients who underwent 1-level and 2-level CDR were retrospectively analyzed. Clinical outcomes were evaluated using scores on the Japanese Orthopaedic Association (JOA), Visual Analogue Scale (VAS), and Neck Disability Index (NDI). The craniocervical sagittal alignment parameters, including the C0-C2 Cobb angle, C2-C7 Cobb angle, C2 slope, T1 slope, C2-C7 sagittal vertical axis (SVA), C1-C7 SVA, the center of gravity of the head (CGH)-C7 SVA, and range of motion (ROM) at the surgical segments were measured. RESULTS: A total of 169 patients were involved. Significantly lower pre- and postoperative C2 slope and CGH-C7 SVA were found in arthroplasty levels with better ROMs. Patients with a higher preoperative C2 slope and CGH-C7 SVA had lower cervical lordosis and ROM after surgery. There were no significant differences in the clinical outcomes between patients with different sagittal balance statuses. C2-C7 SVA and CGH-C7 SVA were significantly associated with radiographic adjacent segment pathology (rASP). CONCLUSION: Craniocervical sagittal balance is associated with cervical lordosis and ROM at the index level after CDR. A higher preoperative SVA is related to the presence and progression of rASP. A relationship between sagittal alignment and clinical outcomes was not observed.

Metastatic Ceruminous Adenoid Cystic Carcinoma of the Lumbar Spine Causing Neurological Compromise: A Case Report.

Background: Ceruminous glands are modified apocrine glands of the external auditory canal (EAC). Malignant tumours within the ceruminous glands are extremely rare, and the most common histological type is adenoid cystic carcinoma (ADCC), which has high recurrence and metastasis risks. Although a few cases of metastatic ADCC from other head and neck glands have been reported, metastatic ADCC originating from the ceruminous gland are extremely rare. Case presentation: We present an unusual case of spinal metastases of ADCC from ceruminous glands. A 61-year-old woman complaining of low back pain and both lower limbs pain was referred to our department. The primary ceruminous tumour was resected 26 years ago and recurred 6 years later, which was treated by radiotherapy. Three years ago, she presented with low back pain and was diagnosed as multiple lungs and bone metastases. The patient underwent tumour excision, decompression and fusion. The biopsy revealed metastatic ADCC. The symptoms were alleviated after surgery. Conclusions: ADCC of EAC is a pernicious malignant tumour that is characterized by slow-growing patterns and a high predisposition to recurrence and metastasis. Differential diagnoses of ADCC and benign tumours in the EAC are challenging, particularly at early stages. We report a rare case of ceruminous ADCC with a prolonged clinical history as well as spinal metastasis and highlight the significance of regular follow-ups for patients undergoing tumour excision in the EAC.

Biomechanical Evaluation of Intervertebral Fusion Process After Anterior Cervical Discectomy and Fusion: A Finite Element Study.

Introduction: Anterior cervical discectomy and fusion (ACDF) is a widely accepted surgical procedure in the treatment of cervical radiculopathy and myelopathy. A solid interbody fusion is of critical significance in achieving satisfactory outcomes after ACDF. However, the current radiographic techniques to determine the degree of fusion are inaccurate and radiative. Several animal experiments suggested that the mechanical load on the spinal instrumentation could reflect the fusion process and evaluated the stability of implant. This study aims to investigate the biomechanical changes during the fusion process and explore the feasibility of reflecting the fusion status after ACDF through the load changes borne by the interbody fusion cage. Methods: The computed tomography (CT) scans preoperatively, immediately after surgery, at 3 months, and 6 months follow-up of patients who underwent ACDF at C5/6 were used to construct the C2-C7 finite element (FE) models representing different courses of fusion stages. A 75-N follower load with 1.0-Nm moments was applied to the top of C2 vertebra in the models to simulate flexion, extension, lateral bending, and axial rotation with the C7 vertebra fixed. The Von Mises stress at the surfaces of instrumentation and the adjacent intervertebral disc and force at the facet joints were analyzed. Results: The facet contact force at C5/6 suggested a significantly stepwise reduction as the fusion proceeded while the intradiscal pressure and facet contact force of adjacent levels changed slightly. The stress on the surfaces of titanium plate and screws significantly decreased at 3 and 6 months follow-up. A markedly changed stress distribution in extension among three models was noted in different fusion stages. After solid fusion is achieved, the stress was more uniformly distributed interbody fusion in all loading conditions. Conclusions: Through a follow-up study of 6 months, the stress on the surfaces of cervical instrumentation remarkably decreased in all loading conditions. After solid intervertebral fusion formed, the stress distributions on the surfaces of interbody cage and screws were more uniform. The stress distribution in extension altered significantly in different fusion status. Future studies are needed to develop the interbody fusion device with wireless sensors to achieve longitudinal real-time monitoring of the stress distribution during the course of fusion.

Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery.

Despite strong evidence that human genetic variants affect the expression of many key transcription factors involved in autoimmune diseases, establishing biological links between non-coding risk variants and the gene targets they regulate remains a considerable challenge. Here, we combine genetic, epigenomic, and CRISPR activation approaches to screen for functional variants that regulate IRF8 expression. We demonstrate that the locus containing rs2280381 is a cell-type-specific enhancer for IRF8 that spatially interacts with the IRF8 promoter. Further, rs2280381 mediates IRF8 expression through enhancer RNA AC092723.1, which recruits TET1 to the IRF8 promoter regulating IRF8 expression by affecting methylation levels. The alleles of rs2280381 modulate PU.1 binding and chromatin state to regulate AC092723.1 and IRF8 expression differentially. Our work illustrates an integrative strategy to define functional genetic variants that regulate the expression of critical genes in autoimmune diseases and decipher the mechanisms underlying the dysregulation of IRF8 expression mediated by lupus risk variants.

Urinary galectin-3 binding protein (G3BP) as a biomarker for disease activity and renal pathology characteristics in lupus nephritis.

OBJECTIVE: There is an urgent need to identify novel biomarkers of LN to reflect renal histological changes. This study aims to investigate urinary G3BP levels in LN patients and their association with renal disease activity both clinically and pathologically. METHODS: This is a cross-sectional study. A total of 119 lupus nephritis patients were recruited. Thirty patients with chronic kidney diseases (CKD) and 27 healthy volunteers were also recruited as controls. Urinary G3BP was tested by ELISA. Renal histopathology was reviewed by an experienced renal pathologist. Other clinical variables were collected through chart review. RESULTS: The levels of uG3BP were significantly increased in active LN patients compared to those in inactive LN (p<0.001), CKD patients (p=0.01), and healthy controls (p<0.001). ROC analysis indicated a good discrimination ability of uG3BP to differentiate active LN from CKD patients (AUC=0.7), inactive LN (AUC=0.76), or healthy controls (AUC=0.87). uG3BP was positively correlated with SLEDAI (ρ=0.352, p<0.001), rSLEDAI (ρ=0.302, p<0.001), and SLICC RAS (ρ=0.465, p<0.001), indicating a role as a biomarker of disease activity. It also correlated with clinical parameters, including 24-h urine protein, ESR, and serum C3 levels. In patients with 24-h urine protein > 3.0 g/24h, uG3BP levels were higher in proliferative LN than in membranous LN (p=0.04). They could discriminate the two pathogenic types of LN (AUC=0.72), and they also positively correlated with AI (ρ=0.389, p=0.008) and scores of hyaline deposits (ρ=0.418, p=0.006). While in patients with 24-h urine protein ≤ 3.0 g/24h, uG3BP levels were not significantly different between proliferative and membranous LN, and there was no apparent relationship between uG3BP levels with AI or with scores of hyaline deposits, but they correlated positively with scores of cellular/fibrocellular crescents (ρ=0.328, p=0.04). CONCLUSION: uG3BP is a non-invasive biomarker for clinically and histologically reflecting disease activity. It is associated with active histological changes and can be used as a surrogate biomarker when the renal biopsy is impractical.

Association Between Health Literacy and Enhanced Recovery After Surgery Protocol Adherence and Postoperative Outcomes Among Patients Undergoing Colorectal Cancer Surgery: A Prospective Cohort Study.

BACKGROUND: Low health literacy (HL) adversely affects medical adherence and health outcomes in patients with chronic diseases. However, the association between HL and enhanced recovery after surgery (ERAS) adherence and postoperative outcomes has not been investigated in patients undergoing colorectal surgery. METHODS: The data of all patients from a single academic institution who underwent colorectal surgery on an ERAS pathway from January 2019 to July 2020 were prospectively collected. HL levels were assessed using the Brief Health Literacy Screen (BHLS), a proven tool that was used by surgeons after recruitment. According to the HL score, the participants were categorized into low HL (≤9 points) and high HL (10-15 points) groups. The primary outcome was ERAS adherence. Adherence was measured in 22 perioperative elements, and high adherence was defined as adherence to 17 to 22 elements. Secondary outcomes included postoperative complications, hospital length of stay (LOS), hospital charges, mortality, and readmissions. RESULTS: Of the 865 eligible patients, the high HL group consisted of 329 patients (38.0%), and the low HL group contained 536 patients (62.0%). After propensity score matching (1:1), 240 unique pairs of patients with similar characteristics were selected. Patients with high HL levels had a significantly higher rate of high adherence to ERAS standards than those with low HL levels (55% vs 25.8%; adjusted P < .001). In terms of adherence to each item, high HL levels were significantly associated with higher adherence to preoperative optimization (90.8% vs 71.7%; adjusted P < .001), postoperative gum chewing (59.2% vs 44.6%; adjusted P = .01), early feeding (59.2% vs 31.3%; adjusted P < .001), and early mobilization (56.7% vs 30.4%; adjusted P < .001). In the overall study population, adjusted logistic regression analyses also showed that high HL levels were associated with a significantly increased rate of high adherence when compared with low HL levels (adjusted odds ratio [OR], 3.57; 95% confidence interval (CI), 2.50-5.09; P < .001). In addition, low HL levels were associated with a significantly higher incidence of postoperative complications (32.1% vs 20.8%; P < .01), longer hospital LOS (9 [interquartile range {IQR}, 7-11] vs 7 [IQR, 6-9] d; P < .001), and higher hospital charges (10,489 [IQR, 8995-11942] vs 8466 [IQR, 7733-9384] dollar; P < .001) among propensity-matched patients. However, there were no differences in the mortality and readmission rates between the HL groups. CONCLUSIONS: Low HL levels were associated with lower adherence to ERAS elements among propensity-matched patients undergoing colorectal surgery.

Impact of enhanced recovery after surgery protocol compliance on patients' outcome in benign hysterectomy and establishment of a predictive nomogram model.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been shown to improve clinical outcomes after surgery. Considering the importance of patient experience for patients with benign surgery, this study evaluated whether improved compliance with ERAS protocol modified for gynecological surgery which recommended by the ERAS Society is associated with better clinical outcomes and patient experience, and to determine the influence of compliance with each ERAS element on patients' outcome after benign hysterectomy. METHODS: A prospective observational study was performed on the women who underwent hysterectomy between 2019 and 2020. A total of 475 women greater 18 years old were classified into three groups according to their per cent compliance with ERAS protocols: Group I: < 60% (148 cases); Group II:≥60 and < 80% (160 cases); Group III: ≥80% (167 cases). Primary outcome was the 30-day postoperative complications. Second outcomes included QoR-15 questionnaire scores, patient satisfaction on a scale from 1 to 7, and length of stay after operation. After multivariable binary logistic regression analyse, a nomogram model was established to predict the incidence of having a postoperative complication with individual ERAS element compliance. RESULTS: The study enrolled 585 patients, and 475 completed the follow-up assessment. Patients with compliance over 80% had a significant reduction in postoperative complications (20.4% vs 41.2% vs 38.1%, P < 0.001) and length of stay after surgery (4 vs 5 vs 4, P < 0.001). Increased compliance was also associated with higher patient satisfaction and QoR-15 scores (P < 0.001),. Among the five dimensions of the QoR-15, physical comfort (P < 0.05), physical independence (P < 0.05), and pain dimension (P < 0.05) were better in the higher compliance groups. Minimally invasive surgery (MIS) (P < 0.001), postoperative nausea and vomiting (PONV) prophylaxis (P < 0.001), early mobilization (P = 0.031), early oral nutrition (P = 0.012), and early removal of urinary drainage (P < 0.001) were significantly associated with less complications. Having a postoperative complication was better predicted by the proposed nomogram model with high AUC value (0.906) and sensitivity (0.948) in the cohort. CONCLUSIONS: Improved compliance with the ERAS protocol was associated with improved recovery and better patient experience undergoing hysterectomy. MIS, PONV prophylaxis, early mobilization, early oral intake, and early removal of urinary drainage were of concern in reducing postoperative complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019178 . Registered on 30/10/2018.

Effects of endplate coverage and intervertebral height change on heterotopic ossification following cervical disc replacement.

BACKGROUND: Heterotopic ossification (HO) is a common complication after cervical disc replacement (CDR). Biomechanical factors including endplate coverage and intervertebral disc height change may be related to HO formation. However, there is a dearth of quantitative analysis for endplate coverage, intervertebral height change and their combined effects on HO. METHODS: Patients who underwent single-level or two-level CDR with Prestige-LP were retrospectively reviewed. Clinical outcomes were evaluated through Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI) score, and visual analogue scale (VAS) score. Radiological data, including the prosthesis-endplate depth ratio, intervertebral height change, posterior heterotopic ossification (PHO) and angular parameters, were collected. Logistic regression analysis was used to identify the potential risk factors. Receiver operating characteristic curves were plotted and the cut-off values of each potential factors were calculated. RESULTS: A total of 138 patients with 174 surgical segments were evaluated. Both the prosthesis-endplate depth ratio (P < 0.001) and post-operative disc height change (P < 0.001) were predictive factors for PHO formation. The area under the curve (AUC) of the prosthesis-endplate depth ratio, disc height change and their combined effects represented by the combined parameter (CP) were 0.728, 0.712 and 0.793, respectively. The risk of PHO significantly increased when the prosthesis-endplate depth ratio < 93.77% (P < 0.001, OR = 6.909, 95% CI 3.521-13.557), the intervertebral height change ≥ 1.8 mm (P < 0.001, OR = 5.303, 95% CI 2.592-10.849), or the CP representing the combined effect < 84.88 (P < 0.001, OR = 10.879, 95% CI 5.142-23.019). CONCLUSIONS: Inadequate endplate coverage and excessive change of intervertebral height are both potential risk factors for the PHO after CDR. Endplate coverage less than 93.8% or intervertebral height change more than 1.8 mm would increase the risk of PHO. The combination of these two factors may exacerbate the non-uniform distribution of stress in the bone-implant interface and promote HO development.

Luteolin combined with low-dose paclitaxel synergistically inhibits epithelial-mesenchymal transition and induces cell apoptosis on esophageal carcinoma in vitro and in vivo.

Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial-mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo. The molecular mechanism of inhibiting cell migration and EMT processes may be related to the inhibition of SIRT1, and the mechanism of apoptosis induction is associated with the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway-mediated activation of mitochondrial apoptotic pathway.