Quantum Implementation of the SAND Algorithm and Its Quantum Resource Estimation for Brute-Force Attack.

The SAND algorithm is a family of lightweight AND-RX block ciphers released by DCC in 2022. Our research focuses on assessing the security of SAND with a quantum computation model. This paper presents the first quantum implementation of SAND (including two versions of SAND, SAND-64 and SAND-128). Considering the depth-times-width metric, the quantum circuit implementation of the SAND algorithm demonstrates a relatively lower consumption of quantum resources than that of the quantum implementations of existing lightweight algorithms. A generalized Grover-based brute-force attack framework was implemented and employed to perform attacks on two versions of the SAND algorithm. This framework utilized the g-database algorithm, which considered different plaintext-ciphertext pairs in a unified manner, reducing quantum resource consumption. Our findings indicate that the SAND-128 algorithm achieved the NIST security level I, while the SAND-64 algorithm fell short of meeting the requirements of security level I.

TRIM21-mediated Sohlh2 ubiquitination suppresses M2 macrophage polarization and progression of triple-negative breast cancer.

Lung metastasis is the major cause of death in patients with triple-negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) represent the M2-like phenotype with potent immunosuppressive activity, and play a pro-tumor role in TNBC lung metastasis. Sohlh2 belongs to the basic helix-loop-helix transcription factor family. However, its role in macrophages polarization remains unknown, especially in TNBC progression. Here we demonstrated that Sohlh2 overexpression promoted M2 macrophage polarization. Moreover, high expression of Sohlh2 in M2-like macrophage enhanced TNBC cell growth, migration and lung metastasis in vivo and in vitro. Mechanistically, we revealed that Sohlh2 functioned through up-regulating LXRα, ABCA1, ABCG1 expression and disturbing the lipid homeostasis on the membrane of macrophages. Sohlh2 could directly bind to the promoter of LXRα and promote its transcription activity. E3 ubiquitin ligase TRIM21 promoted Sohlh2 ubiquitination and degradation, and suppressed M2 macrophage polarization and TNBC progression. Collectively, our findings suggested that Sohlh2 in macrophage could be a novel therapeutic target for TNBC metastatic treatment.

Sohlh2 promotes pulmonary fibrosis via repression of p62/Keap1/Nrf2 mediated anti-oxidative signaling pathway.

Disturbance in the redox balance of alveolar epithelial cells (AECs) was considered as a causal factor for pulmonary fibrosis. The regulatory mechanisms of redox hemostasis in the development of pulmonary fibrosis remain largely unknown. Using a type II AEC-specific Sohlh2 conditional knock-in (CKI) mouse model, we found that Sohlh2, a basic HLH transcription factor, accelerated age-related pulmonary fibrosis. High-fat diet (HFD) resulted in a tremendous increase in lung inflammation and fibrotic changes in the lung tissues of Sohlh2 CKI mice. Sohlh2 overexpression led to a significant rise of intracellular ROS and apoptosis in the lung, mouse primary AECIIs, and human A549 cells, which was attenuated by ROS inhibitor (NAC). Sohlh2 enhanced oxidative stress via repressing p62/Keap1/Nrf2 mediated anti-oxidative signaling pathway. p62, a direct target of Sohlh2, mediated Sohlh2 effects on ROS generation and apoptosis in A549 cells. Hence, our findings elucidate a pivotal mechanism underlying oxidative stress-induced pulmonary fibrosis, providing a framework for aging-related disorder interventions.

A Cross-Sectional Descriptive Study on the Attitudes Towards Patient Safety and Influencing Factors of Nurses in Infectious Diseases Wards.

Background: Patient safety is an important aspect of healthcare delivery and is critical to healthcare quality. An assessment of the attitudes of nursing staff in infectious diseases wards towards patient safety may identify deficiencies and allow for the development of educational programmes to train nursing staff to participate in good patient safety practices. Objective: To explore the current situation and influencing factors on nurses' attitudes towards patient safety in infectious diseases wards. Methods: This cross-sectional study enrolled 446 nurses from infectious diseases wards in eight hospitals in the Hebei Province to participate in an electronic questionnaire survey from October to December 2020. The Chinese version of the safety attitude questionnaire was used to gather the opinions of these participants, and SPSS 22.0 statistical software was used to analyse the data. Results: The average score of safety attitudes towards patients was 3.59 ± 0.30. The scores for each dimension, from high to low, were as follows: management perception: 3.77 ± 0.42 points, pressure perception: 3.77 ± 0.42 points, safety atmosphere: 3.57 ± 0.43 points, job satisfaction: 3.57 ± 0.43 points, teamwork: 3.55 ± 0.50 points and working conditions: 3.50 ± 0.45 points. The results of the multiple stepwise regression analysis showed that the influential factors on nurses' attitudes towards patient safety in infectious diseases wards were as follows: night shift working (ß = 11.885, P = 0.000), years of nursing experience (ß = 2.862, P = 0.001), education level (ß = 4.462, P = 0.001) and marital status (ß = 3.871, P = 1.002), which together explained 33.5% of the total variance. Conclusion: Nurses' attitudes towards patient safety in infectious diseases wards were moderately high. Night shift work, years of nursing experience, education level and marital status affected nurses' attitudes towards patient safety. Managers should focus on these groups of nurses and improve their working conditions and job satisfaction to further enhance patient safety.

The impact of disease time, cervical alignment and range of motion on cervical vertebral Hounsfield unit value in surgery patients with cervical spondylosis.

STUDY DESIGN: This study was a retrospective review. OBJECTIVE: Bone mineral density (BMD) at the surgical site is associated with complications of surgical internal fixation, and it is very important to study the cervical BMD of patients with cervical spondylosis who need surgery and the related factors that affect cervical BMD. It is still unclear about the age-related influence of disease time, cervical alignment and range of motion (ROM) on cervical vertebral Hounsfield unit (HU) value. METHODS: This retrospective study was conducted on patients who underwent cervical surgery at one institution between January 2014 and December 2021. Age, sex, body mass index (BMI), disease type, comorbidities, neck pain, disease time, C2-7 Cobb angle (CA), cervical ROM and the C2-C7 vertebral HU value were recorded. The association between cervical HU value and each parameter of interest was assessed using the Pearson correlation coefficient. Multivariable linear regression analysis was performed to examine the relative influence of the multiple factors on cervical vertebral HU value. RESULTS: Among patients younger than 50 years old, the HU value of the cervical vertebral in females was higher than that of males, but after the age of 50 years, the value of females was lower than that of males and decreased significantly after 60 years old. In addition, cervical HU value was significantly correlated with the disease time, flexion CA and ROM. Our age-related subgroup of multivariate linear regression analyses shows that disease time and flexion CA negatively affected the C6-7 HU value in more than 60-year-old males and in more than 50-year-old females. CONCLUSIONS: Disease time and flexion CA were negatively affecting the C6-7 HU values in more than 60-year-old males and in more than 50-year-old females. More attention should be paid to bone quality in cervical spondylosis patients with longer disease time and larger convex of flexion CA.

New insight into desorption behavior and mechanism of oil from aged oil-contaminated soil in microemulsion.

The intractable nature of oil-contaminated soil (OS) constitutes the chief limiting factor for its remediation. Herein, the aging effect (i.e., oil-soil interactions and pore-scale effect) was investigated by analyzing the properties of aged OS and further demonstrated by investigating the desorption behavior of the oil from the OS. XPS was performed to detect the chemical environment of N, O, and Al, indicating the coordination adsorption of carbonyl groups (oil) on the soil surface. Alterations in the functional groups of the OS were detected using FT-IR, indicating that the oil-soil interactions were enhanced via wind-thermal aging. SEM and BET were used to analyze the structural morphology and pore-scale of the OS. The analysis revealed that aging promoted the development of the pore-scale effect in the OS. Moreover, the desorption behavior of oil molecules from the aged OS was investigated via desorption thermodynamics and kinetics. The desorption mechanism of the OS was elucidated via intraparticle diffusion kinetics. The desorption process of oil molecules underwent three stages: film diffusion, intraparticle diffusion, and surface desorption. Owing to the aging effect, the latter two stages constituted the major steps for controlling oil desorption. This mechanism provided theoretical guidance to apply microemulsion elution for remedying industrial OS.

Sohlh2 Regulates the Stemness and Differentiation of Colon Cancer Stem Cells by Downregulating LncRNA-H19 Transcription.

Colon cancer stem cells (CSC) are tumor-initiating cells that drive tumorigenesis and progression through self-renewal and various differentiation potency. Therefore, the identification of factors critical for colon CSC function is vital for the development of therapies. Sohlh2 belongs to the superfamily of bhlh transcription factors and serves as a tumor suppressor in several tumors. The role of Sohlh2 in CSCs remains unknown. Here we demonstrated that Sohlh2 was related to the inhibition of LncRNA-H19/miR-141/ß-catenin signaling and led to the consequent suppression of colon CSC stemness and the promotion of colon CSC differentiation in vitro and in vivo. Moreover, Sohlh2 could directly bind to the promoter of LncRNA-H19 and repress its transcription activity. LncRNA-H19 mediated the effects of Sohlh2 on colon CSC stemness and differentiation. Clinically, we observed a significant inverse correlation between Sohlh2 and LncRNA-H19, ß-catenin, Lgr5, CD133 expression levels, and positive correlation between Sohlh2 and MUC2, TFF2 expression in colon cancer tissues. Collectively, our findings suggest an important role of the Sohlh2/LncRNA-H19/miR-141/ß-catenin pathway in regulating colon CSC stemness and differentiation, suggesting potential therapeutic targets for colon cancer. IMPLICATIONS: This study identifies that Sohlh2 directly manipulates LncRNA-H19 transcription and suppresses the ß-catenin signaling pathway and the Sohlh2/LncRNA-H19/miR-141/ß-catenin signaling pathway plays an essential role in the stemness of colon CSCs.

Value of plasma vitamin D level and nomogram model for predicting the prognosis of patients with small cell lung cancer treated with platinum plus etoposide as first-line chemotherapy.

BACKGROUND: To assess the value of plasma vitamin D level and nomogram model in predicting the prognosis of patients with small cell lung cancer (SCLC) treated with platinum plus etoposide (PPE) as first-line chemotherapy. METHODS: In this retrospective study, we included 178 patients with SCLC. The data of 25(OH)D level, basic clinical information, overall survival (OS) and progression-free survival (PFS) were collected. Moreover, a nomogram was constructed to predict the prognosis of the patients. RESULTS: The median OS value for patients with 25(OH)D < 10 ng/mL was 12.5 months. The median PFS value was 6.6 months. Sex, smoking status, clinical stage, and plasma vitamin D were independent prognostic predictors. Besides, the decision curve analysis and receiver operating characteristic curve indicated that the nomogram prediction models showed positive clinical benefit. CONCLUSIONS: The plasma vitamin D level is of great significance in prognosis of patients with SCLC. The construction of nomograms is beneficial in predicting the prognosis of patients with SCLC treated with PPE.

Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

BACKGROUND: Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. METHODS: The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. RESULTS: Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7-Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7-Hs and CK7+Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7+Hs (2 +) and CK7+Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7+Hs (2 +) and CK7+Hs (1 +) into CK7+Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7+Hs and CK7-Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7+Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363-30.162), 4.145 (95% CI 1.898-9.052) and 3.247 (95% CI 1.556-6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7+Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively. CONCLUSION: CK7+Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

Intraoperative neurophysiologic monitoring alteration during en bloc laminectomy surgery for thoracic ossification of ligamentum flavum.

Background: There is real risk during en bloc resection for the treatment of thoracic ossification of ligamentum flavum (TOLF). Intraoperative neurophysiologic monitoring (IONM) has been applied to monitor neurologic functional integration of the spinal cord during surgery. However, the IONM outcome and its relationship with clinical results still needs to be investigated. The purpose of this study is to evaluate the effectiveness and usefulness of IONM in en bloc laminectomy for TOLF. Methods: Data from a total of 68 patients with TOLF who received en bloc resection was collected for this retrospective study. IONM of somatosensory-evoked potentials (SSEPs) and motor-evoked potentials (MEPs) were analyzed in different patterns of signal alerts, i.e. alert in either MEPs or SSEPs, alert in both MEPs and SSEPs, permanent alert, or recovery during surgery. Postoperative motor and sensory neurological function was evaluated in each patient immediately after surgery and at 12-month follow-up after surgery. The relationship of IONM outcomes and postoperative neurologic function were observed. Results: Fifty of 68 patients did not present significant changes over alert criteria of IONM, neither SSEPs nor MEPs. Those 50 patients without IONM alerts did not show post-operative neurologic deterioration. Four patients presented alert of IONM in a single modality, while 2 patients showed only SSEP alert and 2 patients showed only MEP alert. Fourteen patients showed alerts in both SSEP and MEP, while 8 patients showed one or both signals return to normal during surgery and other 6 showed permanent abnormal electrophysiologic signals to the end of surgery. In the follow-up neurologic test, 3 patients presented transient neurologic complications from among 8 patients with both SSEP and MEP alerts and recovery during surgery. Six patients without recovery of IONM showed permanent neurologic complications after surgery. Conclusions: Results of this study prove the effectiveness and usefulness of IONM in in en bloc laminectomy surgery for TOLF. The patterns of IONM changes correlated with postoperative neurologic functions. Special attention must be paid to the rapid loss of IONM without recovery during spinal decompression.

Clinical efficacy and safety of posterior minimally invasive surgery in cervical spondylosis: a systematic review.

BACKGROUND: Posterior minimally invasive surgery has been increasingly used in in recent years for the clinical treatment of cervical spondylosis. However, this treatment remains challenging and has not been comprehensively reported. The aim of this study was to provide a systematic review of posterior minimally invasive treatment for cervical spondylosis to demonstrate the clinical efficacy and safety of this procedure. METHOD: We collected information from patients with myelopathy or radiculopathy cervical spondylosis who underwent posterior minimally invasive surgery and verified the clinical efficacy and safety of these surgeries with different measurement indicators from five electronic databases: the Nurick, visual analog scale score, Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), EuroQol Five Dimensions Questionnaire (EQ-5D) score, Short-Form Health Survey Physical Component Summary (SF12-PCS) questionnaire score, Short-Form Health Survey Mental Component Summary (SF12-MCS) questionnaire score, and the MOS item short form health survey (HF-36) score. The decompression effect, cervical spine stability, average surgery time, surgical blood loss volume, length of hospital stay, and related complications were included in the descriptive analysis. Reporting of this protocol followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines checklist. RESULTS: We identified 14 observational studies of cervical spondylosis with 479 patients, mainly including 197 cases of myelopathy and 207 cases of radiculopathy. Channel and endoscopic techniques were used. This study was certified by PROSPERO: CRD42021290074. Significant improvements in the quantitative indicators (Neck-VAS in 9 studies, JOA in 7 studies, NDIs in 5 studies, Nurick, ARM-VAS, and EQ-5D in 2 studies each, and the SF12-PCS, SF12-MCS, and HF-36 in 1 study each) were observed between pre- and postoperation (P < 0.05), and satisfactory clinical significance was acquired in the descriptive indicators [average surgery time (94.56 ± 37.26 min), blood loss volume (68.78 ± 103.31 ml), average length of stay (2.39 ± 1.20 d), and cervical spine stability after surgery]. Additionally, we showed that there was a 4.9% postoperative complication rate and the types of complications that may occur. CONCLUSION: Posterior minimally invasive surgery is an effective and safe method for the treatment of cervical spondylosis and is a recommended optional surgical procedure for single-segment myelopathy and radiculopathy.

Low cervical vertebral CT value increased early subsidence of titanium mesh cage after anterior cervical corpectomy and fusion.

STUDY DESIGN: This study was a retrospective review. OBJECTIVE: To study the predictive effect of Hounsfield units (HU) value in the cervical vertebral body derived from computed tomography (CT) on the early titanium mesh cage (TMC) subsidence after anterior cervical corpectomy and fusion (ACCF). METHODS: This retrospective study was conducted on patients who underwent ACCF at one institution between January 2014 and December 2018. We collected date included age, gender, body mass index (BMI), disease type, surgical segment, whether merge ACDF, HU value of the vertebral body and endplate, vertebral body height loss, cervical lordosis angle, and cervical sagittal alignment. VAS, JOA, and NDI were used to assess clinical efficacy. Univariate analysis was performed to screen the influencing factors of TMC subsidence, and then logistic regression was used to find out the independent risk factors. The ROC curve and area under curve (AUC) were used to analyze the HU value to predict the TMC subsidence. RESULTS: A total of 85 patients who accepted ACCF were included in this study, and early titanium mesh cage subsidence was demonstrated in 29 patients. The subsidence rate was 34.1%. The JOA, VAS, and NDI scores significantly improved in both groups after the operation. Between the subsidence and non-subsidence groups, there were significant differences in age, intervertebral distraction height, and HU value in both upper and lower vertebral body and endplate. The logistic regression analysis proved that the HU value of the lower vertebral body was an independent risk of TMC subsidence, the AUC was 0.866, and the most appropriate threshold of the HU value was 275 (sensitivity: 87.5%, specificity: 79.3%). CONCLUSION: Preoperative cervical CT value is an independent correlative factor for early TMC subsidence after ACCF, and patients with a low CT value of the inferior vertebral body of the operative segment have a higher risk of TMC subsidence in the early postoperative period. TRIAL REGISTRATION: This study is undergoing retrospective registration.

MiR-25 enhances autophagy and promotes sorafenib resistance of hepatocellular carcinoma via targeting FBXW7.

Sorafenib resistance is a major challenge in the treatment of patients with advanced hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) are a large family of non-coding RNA molecules, which is an important mechanism of drug resistance. We previously found that knockdown of miR-25 increased the sensitivity of TRAIL-induced apoptosis in liver cancer stem cells. We aimed to study the effects of miR-25 on sorafenib resistance of HCC and the underlying mechanisms. In the present study, we analyzed the expression of miR-25 between HCC and normal tissues and predicted miR-25 target genes through databases. After transfecting miR-25 mimics, inhibitor or FBXW7 Plasmid, CCK-8 and flow cytometry assay was performed to determine the sorafenib resistance. We performed LC3-dual-fluorescence assay and Western blotting to detect the autophagy levels. The expression of miR-25 was upregulated in human HCC tissues and was associated with tumor pathological grade, clinic staging, and lymphatic metastasis. MiR-25 enhanced sorafenib resistance of HCC cells and autophagy. FBXW7 is the direct target of miR-25. Overexpression of FBXW7 could reverse the increase of sorafenib resistance caused by miR-25 mimics. Our results suggested that miR-25 increased the sorafenib resistance of HCC via inducing autophagy. In addition, miR-25 decreases the expression of FBXW7 protein to regulate autophagy. Therefore, miR-25 may represent a novel therapeutic target for the treatment of HCC.

A2M is a potential core gene in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a type of malignant tumor ranking the second in the incidence of primary liver cancer following hepatocellular carcinoma. Both the morbidity and mortality have been increasing in recent years. Small duct type of ICC has potential therapeutic targets. But overall, the prognosis of patients with ICC is usually very poor. METHODS: To search latent therapeutic targets for ICC, we programmatically selected the five most suitable microarray datasets. Then, we made an analysis of these microarray datasets (GSE26566, GSE31370, GSE32958, GSE45001 and GSE76311) collected from the Gene Expression Omnibus (GEO) database. The GEO2R tool was effective to find out differentially expressed genes (DEGs) between ICC and normal tissue. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were executed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v 6.8. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyze protein-protein interaction of these DEGs and protein-protein interaction of these DEGs was modified by Cytoscape3.8.2. Survival analysis was performed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool. RESULTS: A total of 28 upregulated DEGs and 118 downregulated DEGs were screened out. Then twenty hub genes were selected according to the connectivity degree. The survival analysis results showed that A2M was closely related to the pathogenesis and prognosis of ICC and was a potential therapeutic target for ICC. CONCLUSIONS: According to our study, low A2M expression in ICC compared to normal bile duct tissue was an adverse prognostic factor in ICC patients. The value of A2M in the treatment of ICC needs to be further studied.

Mechanism of IDH1-R132H mutation in T cell acute lymphoblastic leukemia mouse model via the Notch1 pathway.

T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignant disease. Isocitrate Dehydrogenase 1-R123 (IDH1-R132 H) is related to T-ALL progression. This study explored the role of IDH1-R132H in T-ALL. Molt-4 cells with IDH1-R132H mutation were constructed by retroviral transfection of IDH1-R132H and T-ALL xenotransplantation mouse model was established by injection of Molt-4 cells through the tail vein. Infiltration of the liver, spleen, and bone marrow and the percentage of CD45-positive T-ALL cells in them were detected. Cell proliferation, apoptosis, and invasion were evaluated after the intervention of Notch1, PTEN, or PI3K expression. The leukocyte number was increased, the spleen was enlarged, infiltration in bone marrow, spleen, and liver tissue was worsened and the percentage of hCD45-positive T-ALL cells was increased by IDH1-R132H mutation, which promoted T-ALL deterioration. IDH1-R132H mutation promoted proliferation, invasion, and inhibited apoptosis of T-ALL cells, which were reversed by inhibition of Notch1. IDH1-R132H mutation upregulated HES1 expression and downregulated PTEN expression by activating the Notch1 pathway, while inhibition of Notch1 reversed these changes. PTEN inhibited the PI3K/AKT pathway activation. PTEN overexpression reversed IDH1-R132H mutation effect on promoting malignant behaviors of T-ALL cells. IDH1-R132H mutation inhibited PTEN expression by activating the Notch1/HES1 pathway, activated the PI3K/AKT pathway, thus promoting malignant behaviors of T-ALL cells.

Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a.

BACKGROUND: Renal cell carcinoma is the most common malignant tumor of the kidney. The 5-year survival of renal cell carcinoma with distant metastasis is very low. Sohlh2 is a newly discovered tumor suppressor gene playing inhibitory roles in a variety of tumors, but its role in renal cell carcinoma has not been reported. METHODS: To clarify the role of Sohlh2 in the occurrence and development of renal cell carcinoma, we constructed stably transfected human renal cell carcinoma cell lines with Sohlh2 overexpression and Sohlh2 knockdown, separately. First, we studied the effects of Sohlh2 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of renal cell carcinoma cells in vitro and in vivo. Then, we detected whether Sohlh2 functions through DNMT3a/Klotho using Western blotting, qPCR, and Cell Counting Kit-8 (CCK-8) assay. Finally, we collected 40 resected renal cell carcinoma samples to study the relevance between Sohlh2, DNMT3a, and Klotho by immunohistochemistry. RESULTS: Our results showed that Sohlh2 was downregulated in renal cell carcinoma, and its expression level was negatively correlated with tumor staging. Both in vitro and in vivo experiments confirmed that Sohlh2 overexpression inhibited the proliferation, migration, invasion, metastasis, and EMT of renal cell carcinoma. Sohlh2 functions through demethylation of Klotho by downregulating the expression of DNA methyltransferase of DNMT3a. In renal cell carcinoma, Sohlh2 was positively correlated with Klotho and negatively correlated with DNMT3a. CONCLUSION: Sohlh2 functions as a tumor suppressor gene in renal cell carcinoma by demethylation of Klotho via DNMT3a. Sohlh2 correlated with Klotho positively and with DNMT3a negatively in renal cell carcinoma. Our study suggests that Sohlh2 and DNMT3a/Klotho can be used as potential targets for the clinical treatment of renal cell carcinoma.

Progression Prediction of Mild Cervical Spondylotic Myelopathy by Somatosensory-evoked Potentials.

STUDY DESIGN: Retrospective study to correlate classification of somatosensory-evoked potentials (SEPs) with symptomatic progress of patients with mild cervical spondylotic myelopathy (CSM). OBJECTIVE: The aim of this study was to evaluate the usefulness of SEPs for predicting symptomatic progress of mild CSM. SUMMARY OF BACKGROUND DATA: SEPs have been used for clinical diagnosis and intraoperative neuromonitoring in patients with CSM. However, the prognostic value of SEPs in predicting the progression of CSM remains unclear. METHODS: A total of 200 patients with a clinical diagnosis of mild CSM were enrolled between September 2014 and February 2018. All patients received clinical assessment with the modified Japanese Orthopedic Association scale (mJOA), magnetic resonance imaging, and SEP tests in the first clinical visit and at 1-year follow-up. A classification of upper and lower limbs SEP was developed. At 1-year follow-up, patients with symptom decline >2 points in mJOA were considered progressive myelopathy cases. The relationship of progressive myelopathy and classifications of SEP was investigated. RESULTS: Fifty-four of 200 cases presented with progressive myelopathy. The incidence of progressive myelopathy was 2.6%, 27.7%, 23.8%, 86.7%, and 100% in Class I, II, III, IV, and V of upper SEPs, respectively, and 18.8%, 39.4%, 42.3%, and 62.5% in Class I, II, III, and IV of lower SEPs, respectively. For the combination classification of upper and lower SEPs, the incidence of progressive myelopathy was 0%, 13.7%, 24.3%, 91.1%, and 100% in Class I, II, III, IV, and V, respectively. There was a significant correlation of the incidence of progressive myelopathy with SEP classification for the upper SEPs (r = 0.94, P < 0.01) and the combination SEPs (r = 0.95, P < 0.01). CONCLUSION: The incidence of progressive degenerative myelopathy increased with the upper and combination SEP classifications. Thus, classification of SEPs could predict the clinical decline in mJOA in CSM, reflecting the probability of worsening of myelopathy. LEVEL OF EVIDENCE: 4.

Lower mean platelet volume is a risk indicator of hepatocellular carcinoma recurrence following liver transplantation.

BACKGROUND: Lower mean platelet volume (MPV) is an indicator of platelet activity in the setting of tumor development. This study was to assess the relationship between preoperative MPV and survival outcomes of patients with hepatocellular carcinoma (HCC) following liver transplantation (LT). METHODS: The demographic and clinical characteristics of 304 HCC patients following LT were retrieved from an LT database. All the patients were divided into the normal and lower MPV groups according to the median MPV. The factors were first analyzed using a Kaplan-Meier survival analysis, then the factors with P < 0.10 were selected for multivariate Cox regression analysis and were used to define the independent risk factors for poor prognosis. RESULTS: The 1-, 3-, and 5-year tumor free survival was 95.34%, 74.67% and 69.29% in the normal MPV group, respectively, and 95.40%, 59.97% and 42.94% in the lower MPV group, respectively (P < 0.01). No significant difference was observed in post-LT complications between the normal and lower MPV groups. Portal vein tumor thrombosis (PVTT) [hazard ratio (HR = 2.24; 95% confidence interval: 1.46-3.43; P < 0.01) and lower MPV (HR = 1.58; 95% confidence interval: 1.05-2.36; P = 0.03) were identified as independent prognostic risk factors for recipient survival. CONCLUSION: Preoperative lower MPV is a risk indicator of HCC patients survival outcomes after LT.

Pyogenic liver abscess related to intrahepatic bile duct stones: Difficulties in infectious control and diagnosis of concomitant cholangiocarcinoma.

BACKGROUND AND AIM: Cholangitis, bacteremia, and pyogenic liver abscess (PLA) can be often caused by intrahepatic bile ducts stone (IBDS), which is endemic to South-East Asia. The association between IBDS and cholangiocarcinoma has been well recognized. Concomitant cholangiocarcinoma in the PLA related to IBDS is often missed. METHODS: A case-control study consisting of 64 patients with PLA related to IBDS and 256 control patients with PLA not related to IBDS was used to investigate clinical features of PLA and incidence of concomitant cholangiocarcinoma in patients with PLA related to IBDS. RESULTS: The main imaging manifestations of PLA related to IBDS was cystic-solid lesions and solid lesions. Of seven patients (10.9%) with pathology-proven cholangiocarcinoma in the same area of PLA related to IBDS among 64 patients, only two patients were initially diagnosed as having concomitant cholangiocarcinoma by biopsy, and other five patients diagnosed as acute inflammatory lesion. Within 60 days after onset, the infection-related death rate and recurrence rate in patients with PLA related to IBDS were 12.9% and 20.3%, respectively, whereas in patients with PLA not related to IBDS were 3.9% and 3.1%, respectively. Only 25% of patients with PLA related to IBDS underwent surgery after admission. The main pathogens in PLA patients related to IBDS were Escherichia coli and extended-spectrum beta-lactamase-producing Enterobacteriaceae. CONCLUSIONS: The imaging manifestations of PLA related to IBDS often present cystic-solid or solid lesions. PLA related to IBDS is characterized by high rate of recurrence and infection-related death, difficulty in diagnosis of concomitant cholangicarcinoma.

Biliary diseases as main causes of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.

BACKGROUND & AIMS: Little is known about aetiology and morbidity and clinical characteristics of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. METHODS: An analysis between pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates and those caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae was performed. RESULTS: Among 817 pyogenic liver abscess patients, there were 176 patients (21.5%) with pyogenic liver abscess of biliary origin, and 67 pyogenic liver abscess patients (8.2%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates (mainly Escherichia coli and Klebsiella pneumoniae). Of 176 pyogenic liver abscess patients related to biliary disorders, there were 48 pyogenic liver abscess patients (27.3%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Within 67 pyogenic liver abscess patients caused by Enterobacteriaceae expressing extended-spectrum beta-lactamases, the occurrences of 48 pyogenic liver abscess patients (71.6%) were associated with biliary disorders. When compared with pyogenic liver abscess patients caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae, there were significantly greater incidences of polymicrobial infections, bacteremia, pulmonary infection, recurrence and death in pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Carbapenems remain mainstay drugs against extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae. Independent risk factors for occurrence of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae were biliary disorders including extra- and intrahepatic cholangiolithiasis and an abnormal bilioenteric communication between bile and gut, a treatment history of malignancy such as operation and chemotherapy, pulmonary infection, and diabetes mellitus. CONCLUSIONS: Pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates mainly occurs in patients with biliary disorders or with a treatment history of malignancy. The mainstay of treatment remains carbapenems in combination with adequate aspiration or drainage.